relation: http://d-scholarship-dev.library.pitt.edu/28919/
title: Development of mHealth system for supporting self-management and remote consultation of skincare eHealth/ telehealth/ mobile health systems
creator: Parmanto, B
creator: Pramana, G
creator: Yu, DX
creator: Fairman, AD
creator: Dicianno, BE
description: Background: Individuals with spina bifida (SB) are vulnerable to chronic skin complications such as wounds on the buttocks and lower extremities. Most of these complications can be prevented with adherence to self-care routines. We have developed a mobile health (mHealth) system for supporting self-care and management of skin problems called SkinCare as part of an mHealth suite called iMHere (interactive Mobile Health and Rehabilitation). The objective of this research is to develop an innovative mHealth system to support self-skincare tasks, skin condition monitoring, adherence to self-care regimens, skincare consultation, and secure two-way communications between patients and clinicians. Methods: In order to support self-skincare tasks, the SkinCare app requires three main functions: (1) self-care task schedule and reminders, (2) skin condition monitoring and communications that include imaging, information about the skin problem, and consultation with clinician, and (3) secure two-way messaging between the patient and clinician (wellness coordinator). The SkinCare system we have developed consists of the SkinCare app, a clinician portal, and a two-way communication protocol connecting the two. The SkinCare system is one component of a more comprehensive system to support a wellness program for individuals with SB. Results: The SkinCare app has several features that include reminders to perform daily skin checks as well as the ability to report skin breakdown and injury, which uses a combination of skin images and descriptions. The SkinCare app provides reminders to visually inspect one's skin as a preventative measure, often termed a "skin check." The data is sent to the portal where clinicians can monitor patients' conditions. Using the two-way communication, clinicians can receive pictures of the skin conditions, track progress in healing over time, and provide instructions for how to best care for the wound. Conclusions: The system was capable of supporting self-care and adherence to regimen, monitoring adherence, and supporting clinician engagement with patients, as well as testing its feasibility in a long-term implementation. The study shows the feasibility of a long-term implementation of skincare mHealth systems to support self-care and two-way interactions between patients and clinicians.
date: 2015-12-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28919/1/art%253A10.1186%252Fs12911-015-0237-4.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28919/7/licence.txt
identifier:   Parmanto, B and Pramana, G and Yu, DX and Fairman, AD and Dicianno, BE  (2015) Development of mHealth system for supporting self-management and remote consultation of skincare eHealth/ telehealth/ mobile health systems.  BMC Medical Informatics and Decision Making, 15 (1).       
relation: 10.1186/s12911-015-0237-4

relation: http://d-scholarship-dev.library.pitt.edu/28582/
title: The Contribution of Network Organization and Integration to the Development of Cognitive Control
creator: Marek, S
creator: Hwang, K
creator: Foran, W
creator: Hallquist, MN
creator: Luna, B
description: Cognitive control, which continues to mature throughout adolescence, is supported by the ability for well-defined organized brain networks to flexibly integrate information. However, the development of intrinsic brain network organization and its relationship to observed improvements in cognitive control are not well understood. In the present study, we used resting state functional magnetic resonance imaging (RS-fMRI), graph theory, the antisaccade task, and rigorous head motion control to characterize and relate developmental changes in network organization, connectivity strength, and integration to inhibitory control development. Subjects were 192 10–26-y-olds who were imaged during 5 min of rest. In contrast to initial studies, our results indicate that network organization is stable throughout adolescence. However, cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this increased integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response. These results provide compelling evidence that the transition to adult-level inhibitory control is dependent upon the refinement and strengthening of integration between specialized networks. Our findings support a novel, two-stage model of neural development, in which networks stabilize prior to adolescence and subsequently increase their integration to support the cross-domain incorporation of information processing critical for mature cognitive control.
date: 2015-12-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28582/1/journal.pbio.1002328.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28582/3/licence.txt
identifier:   Marek, S and Hwang, K and Foran, W and Hallquist, MN and Luna, B  (2015) The Contribution of Network Organization and Integration to the Development of Cognitive Control.  PLoS Biology, 13 (12).   ISSN 1544-9173     
relation: 10.1371/journal.pbio.1002328

relation: http://d-scholarship-dev.library.pitt.edu/32684/
title: Conditions for multi-functionality in a rhythm generating network inspired by turtle scratching
creator: Snyder, AC
creator: Rubin, JE
description: Rhythmic behaviors such as breathing, walking, and scratching are vital to many species. Such behaviors can emerge from groups of neurons, called central pattern generators, in the absence of rhythmic inputs. In vertebrates, the identification of the cells that constitute the central pattern generator for particular rhythmic behaviors is difficult, and often, its existence has only been inferred. For example, under experimental conditions, intact turtles generate several rhythmic scratch motor patterns corresponding to non-rhythmic stimulation of different body regions. These patterns feature alternating phases of motoneuron activation that occur repeatedly, with different patterns distinguished by the relative timing and duration of activity of hip extensor, hip flexor, and knee extensor motoneurons. While the central pattern generator network responsible for these outputs has not been located, there is hope to use motoneuron recordings to deduce its properties. To this end, this work presents a model of a previously proposed central pattern generator network and analyzes its capability to produce two distinct scratch rhythms from a single neuron pool, selected by different combinations of tonic drive parameters but with fixed strengths of connections within the network. We show through simulation that the proposed network can achieve the desired multi-functionality, even though it relies on hip unit generators to recruit appropriately timed knee extensor motoneuron activity, including a delay relative to hip activation in rostral scratch. Furthermore, we develop a phase space representation, focusing on the inputs to and the intrinsic slow variable of the knee extensor motoneuron, which we use to derive sufficient conditions for the network to realize each rhythm and which illustrates the role of a saddle-node bifurcation in achieving the knee extensor delay. This framework is harnessed to consider bistability and to make predictions about the responses of the scratch rhythms to input changes for future experimental testing.
date: 2015-12-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32684/1/snyder-rubin-turtlescratching.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32684/7/licence.txt
identifier:   Snyder, AC and Rubin, JE  (2015) Conditions for multi-functionality in a rhythm generating network inspired by turtle scratching.  Journal of Mathematical Neuroscience, 5 (1).       
relation: 10.1186/s13408-015-0026-5

relation: http://d-scholarship-dev.library.pitt.edu/28932/
title: Obituary: Mitchell P. Fink
creator: Angus, DC
date: 2015-12-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28932/1/art%253A10.1186%252Fs13054-015-1169-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28932/7/licence.txt
identifier:   Angus, DC  (2015) Obituary: Mitchell P. Fink.  Critical care (London, England), 19.  442 - ?.      
relation: 10.1186/s13054-015-1169-1

relation: http://d-scholarship-dev.library.pitt.edu/28933/
title: Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro
creator: Kolf, CM
creator: Song, L
creator: Helm, J
creator: Tuan, RS
description: Introduction: Adult mesenchymal stem cells (MSCs) are considered promising candidates for cell-based therapies. Their potential utility derives primarily from their immunomodulatory activity, multi-lineage differentiation potential, and likely progenitor cell function in wound healing and repair of connective tissues. However, in vitro, MSCs often senesce and spontaneously differentiate into osteoblasts after prolonged expansion, likely because of lack of regulatory microenvironmental signals. In vivo, osteoblasts that line the endosteal bone marrow surface are in close proximity to MSCs in the marrow stroma and thus may help to regulate MSC fate. Methods: We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM). Results: Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis. Conclusions: These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation.
date: 2015-12-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28933/1/art%253A10.1186%252Fs13287-015-0223-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28933/7/licence.txt
identifier:   Kolf, CM and Song, L and Helm, J and Tuan, RS  (2015) Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro.  Stem Cell Research and Therapy, 6 (1).       
relation: 10.1186/s13287-015-0223-x

relation: http://d-scholarship-dev.library.pitt.edu/28935/
title: The Happy Older Latinos are Active (HOLA) health promotion and prevention study: Study protocol for a pilot randomized controlled trial
creator: Jimenez, DE
creator: Reynolds, CF
creator: Alegría, M
creator: Harvey, P
creator: Bartels, SJ
description: Background: Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at-risk Latinos. Methods/Design: HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). This prevention approach will be tested against a fotonovela, an enhanced psychoeducation control condition, in a sample of Latino elderly with minor or subthreshold depression or anxiety. A total of 60 older Latinos (aged 60+) will be randomized to receive HOLA or the fotonovela. The primary outcomes of interest are recruitment, adherence, retention, and acceptability. Data will also be collected on: preemption of incident and recurrent major depression, generalized anxiety, and social phobia; reduction in depression and anxiety symptom severity; physical functioning; sedentary behaviors; social engagement; and self-efficacy. Discussion: The results of this study could have implications for other high-risk, highly disadvantaged populations. The development of a health promotion intervention designed to prevent common mental disorders could be a means of addressing multiple disparities (for example, mental health outcomes, mental health service use, stigma) among racial/ethnic minority elderly. ClinicalTrials.gov Identifier:NCT02371954. Date of registration: 21 January 2015.
date: 2015-12-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28935/1/art%253A10.1186%252Fs13063-015-1113-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28935/7/licence.txt
identifier:   Jimenez, DE and Reynolds, CF and Alegría, M and Harvey, P and Bartels, SJ  (2015) The Happy Older Latinos are Active (HOLA) health promotion and prevention study: Study protocol for a pilot randomized controlled trial.  Trials, 16 (1).       
relation: 10.1186/s13063-015-1113-3

relation: http://d-scholarship-dev.library.pitt.edu/28934/
title: An observational study identifying obese subgroups among older adults at increased risk of mobility disability: Do perceptions of the neighborhood environment matter?
creator: King, AC
creator: Salvo, D
creator: Banda, JA
creator: Ahn, DK
creator: Gill, TM
creator: Miller, M
creator: Newman, AB
creator: Fielding, RA
creator: Siordia, C
creator: Moore, S
creator: Folta, S
creator: Spring, B
creator: Manini, T
creator: Pahor, M
description: Background: Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. Methods: The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Results: Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4 %) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4 %) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. Conclusions: The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Trial registration: Clinicaltrials.gov Identifier = NCT01072500
date: 2015-12-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28934/1/art%253A10.1186%252Fs12966-015-0322-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28934/7/licence.txt
identifier:   King, AC and Salvo, D and Banda, JA and Ahn, DK and Gill, TM and Miller, M and Newman, AB and Fielding, RA and Siordia, C and Moore, S and Folta, S and Spring, B and Manini, T and Pahor, M  (2015) An observational study identifying obese subgroups among older adults at increased risk of mobility disability: Do perceptions of the neighborhood environment matter?  International Journal of Behavioral Nutrition and Physical Activity, 12 (1).       
relation: 10.1186/s12966-015-0322-1

relation: http://d-scholarship-dev.library.pitt.edu/38908/
title: Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis
creator: Wright, Aidan G. C.
creator: Beltz, Adriene M.
creator: Gates, Kathleen M.
creator: Molenaar, Peter C. M.
creator: Simms, Leonard J.
description: Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days) of maladaptive behaviors collected from a sample (N = 101) of individuals diagnosed with personality disorders. Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days) we found support for a two-factor Internalizing-Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals) we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Impulsivity structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic.
publisher: Frontiers Media S.A.
date: 2015-12-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/38908/2/fpsyg-06-01914.pdf
identifier:   Wright, Aidan G. C. and Beltz, Adriene M. and Gates, Kathleen M. and Molenaar, Peter C. M. and Simms, Leonard J.  (2015) Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis.  Frontiers in Psychology, 6.   ISSN 1664-1078     
relation: https://www.frontiersin.org/articles/10.3389/fpsyg.2015.01914/full
relation: 10.3389/fpsyg.2015.01914

relation: http://d-scholarship-dev.library.pitt.edu/28938/
title: The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles
creator: Tarabichi, Y
creator: Li, K
creator: Hu, S
creator: Nguyen, C
creator: Wang, X
creator: Elashoff, D
creator: Saira, K
creator: Frank, B
creator: Bihan, M
creator: Ghedin, E
creator: Methé, BA
creator: Deng, JC
description: BACKGROUND: Viral infections such as influenza have been shown to predispose hosts to increased colonization of the respiratory tract by pathogenic bacteria and secondary bacterial pneumonia. To examine how viral infections and host antiviral immune responses alter the upper respiratory microbiota, we analyzed nasal bacterial composition by 16S ribosomal RNA (rRNA) gene sequencing in healthy adults at baseline and at 1 to 2 weeks and 4 to 6 weeks following instillation of live attenuated influenza vaccine or intranasal sterile saline. A subset of these samples was submitted for microarray host gene expression profiling.
date: 2015-12-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28938/1/art%253A10.1186%252Fs40168-015-0133-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28938/7/licence.txt
identifier:   Tarabichi, Y and Li, K and Hu, S and Nguyen, C and Wang, X and Elashoff, D and Saira, K and Frank, B and Bihan, M and Ghedin, E and Methé, BA and Deng, JC  (2015) The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.  Microbiome, 3.  74 - ?.      
relation: 10.1186/s40168-015-0133-2

relation: http://d-scholarship-dev.library.pitt.edu/29371/
title: Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine
creator: Haugaa, H
creator: Gómez, H
creator: Maberry, DR
creator: Holder, A
creator: Ogundele, O
creator: Quintero, AMB
creator: Escobar, D
creator: Tønnessen, TI
creator: Airgood, H
creator: Dezfulian, C
creator: Kenny, E
creator: Shiva, S
creator: Zuckerbraun, B
creator: Pinsky, MR
description: Introduction: Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression. Both nitrite and carbon monoxide (CO) may protect from this reperfusion injury by limiting mitochondrial free radial production. We explored the effects of very small doses of inhaled nitrite and CO on tissue injury in a porcine model of hemorrhagic shock. Methods: Twenty pigs (mean wt. 30.6kg, range 27.2 to 36.4kg) had microdialysis catheters inserted in muscle, peritoneum, and liver to measure lactate, pyruvate, glucose, glycerol, and nitrite. Nineteen of the pigs were bled at a rate of 20ml/min to a mean arterial pressure of 30mmHg and kept between 30 and 40mmHg for 90minutes and then resuscitated. One pig was instrumented but not bled (sham). Hemorrhaged animals were randomized to inhale nothing (control, n=7), 11mg nitrite (nitrite, n=7) or 250ppm CO (CO, n=5) over 30minutes before fluid resuscitation. Mitochondrial respiratory control ratio was measured in muscle biopsies. Repeated measures from microdialysis catheters were analyzed in a random effects mixed model. Results: Neither nitrite nor CO had any effects on the measured hemodynamic variables. Following inhalation of nitrite, plasma, but not tissue, nitrite increased. Following reperfusion, plasma nitrite only increased in the control and CO groups. Thereafter, nitrite decreased only in the nitrite group. Inhalation of nitrite was associated with decreases in blood lactate, whereas both nitrite and CO were associated with decreases in glycerol release into peritoneal fluid. Following resuscitation, the muscular mitochondrial respiratory control ratio was reduced in the control group but preserved in the nitrite and CO groups. Conclusions: We conclude that small doses of nebulized sodium nitrite or inhaled CO may be associated with intestinal protection during resuscitation from severe hemorrhagic shock.
date: 2015-12-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29371/1/art%253A10.1186%252Fs13054-015-0903-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29371/7/licence.txt
identifier:   Haugaa, H and Gómez, H and Maberry, DR and Holder, A and Ogundele, O and Quintero, AMB and Escobar, D and Tønnessen, TI and Airgood, H and Dezfulian, C and Kenny, E and Shiva, S and Zuckerbraun, B and Pinsky, MR  (2015) Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0903-z

relation: http://d-scholarship-dev.library.pitt.edu/29425/
title: Is there a role for music in the ICU?
creator: DellaVolpe, JD
creator: Huang, DT
date: 2015-12-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29425/1/art%253A10.1186%252Fs13054-014-0663-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29425/7/licence.txt
identifier:   DellaVolpe, JD and Huang, DT  (2015) Is there a role for music in the ICU?  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-014-0663-1

relation: http://d-scholarship-dev.library.pitt.edu/28939/
title: Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma
creator: Davar, D
creator: Socinski, MA
creator: Dacic, S
creator: Burns, TF
description: The programmed death 1 (PD-1) receptor is expressed by activated T-cells and engaged by ligands PD-L1 and PD-L2 normally expressed by infiltrating immune cells in response to viral infection. The PD-1/PD-L1 axis is a negative inhibitory pathway that down-regulates T-cells but is also used by tumors to evade anti-tumor immunity. Antibodies targeting PD-1/PD-L1 axis are capable of restoring functional anti-tumor immunity and have demonstrated efficacy in a broad range of tumor types including non-small cell lung cancer in both squamous and adenocarcinoma histologies. Ongoing issues affecting clinical development of these agents include assessment of response, optimal duration of therapy in excellent responders, predictive biomarkers and mechanisms of resistance. In this report, we describe a patient with advanced KRAS mutant heavily pretreated pulmonary adenocarcinoma who developed an excellent response after a single-dose of nivolumab. Pre-treatment tumor was found to have moderate CD3 and PD-L1 positivity by immunohistochemical staining. Evaluation of exceptional responders and non-responders are critical to furthering our understanding of the mechanisms of action (and resistance) to these agents.
date: 2015-12-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28939/1/art%253A10.1186%252Fs40164-015-0029-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28939/7/licence.txt
identifier:   Davar, D and Socinski, MA and Dacic, S and Burns, TF  (2015) Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma.  Experimental Hematology and Oncology, 4 (1).       
relation: 10.1186/s40164-015-0029-7

relation: http://d-scholarship-dev.library.pitt.edu/29411/
title: Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping HAND 2 randomized controlled trial
creator: Reid, ZZ
creator: Regan, S
creator: Kelley, JH
creator: Streck, JM
creator: Ylioja, T
creator: Tindle, HA
creator: Chang, Y
creator: Levy, DE
creator: Park, ER
creator: Singer, DE
creator: Carpenter, KM
creator: Reyen, M
creator: Rigotti, NA
description: Background: Smoking cessation interventions for hospitalized smokers are effective in promoting smoking cessation, but only if the tobacco dependence treatment continues after the patient leaves the hospital. Sustaining tobacco dependence treatment after hospital discharge is a challenge for health care systems. Our previous single-site randomized controlled trial demonstrated the effectiveness of an intervention that facilitated the delivery of comprehensive tobacco cessation treatment, including both medication and counseling, after hospital discharge. We subsequently streamlined the intervention model to increase its potential for dissemination. This new model is being tested in a larger multi-site trial with broader eligibility criteria in order to enroll a more representative sample of hospitalized smokers. This paper describes the trial design and contrasts it with the earlier study. Methods/Design: A 2-arm, 3-site randomized controlled trial is testing the hypothesis that a multi-component Sustained Care intervention is more effective than Standard Care in helping hospitalized cigarette smokers stop smoking after hospital discharge. The trial enrolls adult daily cigarette smokers who are admitted to 1 of 3 participating hospitals in Massachusetts or Pennsylvania. Participants receive the same smoking cessation intervention in the hospital. They are randomly assigned to receive either Standard Care or Sustained Care after hospital discharge. Participants in the Sustained Care arm receive a free 3-month supply of FDA-approved smoking cessation medication and 5 interactive voice response calls that provide tailored motivational messages, medication refills, and access to a live tobacco treatment counselor. Participants in the Standard Care arm receive a smoking cessation medication recommendation and information about community resources. Outcomes are assessed at 1, 3, and 6 months after discharge. The primary outcome is biochemically-validated tobacco abstinence for the past 7 days at 6-month follow-up. Other outcome measures include self-reported tobacco abstinence measures, use of medication and counseling after discharge, hospital readmissions, and program cost-effectiveness. Discussion: We adapted a proven intervention for hospitalized smokers to enhance its potential for dissemination and are testing it in a multi-site trial. Study enrollment data suggests that the trial achieved the goal of recruiting a broader sample of hospitalized smokers. Trial registration: Comparative Effectiveness of Post-Discharge Strategies for Hospitalized Smokers (Helping HAND2) NCT01714323. Registered October 22, 2012.
date: 2015-12-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29411/1/art%253A10.1186%252Fs12889-015-1484-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29411/7/licence.txt
identifier:   Reid, ZZ and Regan, S and Kelley, JH and Streck, JM and Ylioja, T and Tindle, HA and Chang, Y and Levy, DE and Park, ER and Singer, DE and Carpenter, KM and Reyen, M and Rigotti, NA  (2015) Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping HAND 2 randomized controlled trial.  BMC Public Health, 15 (1).       
relation: 10.1186/s12889-015-1484-0

relation: http://d-scholarship-dev.library.pitt.edu/29394/
title: Different contribution of BRINP3 gene in chronic periodontitis and peri-implantitis: A cross-sectional study
creator: Casado, PL
creator: Aguiar, DP
creator: Costa, LC
creator: Fonseca, MA
creator: Vieira, TCS
creator: Alvim-Pereira, CCK
creator: Alvim-Pereira, F
creator: Deeley, K
creator: Granjeiro, JM
creator: Trevilatto, PC
creator: Vieira, AR
description: Background: Peri-implantitis is a chronic inflammation, resulting in loss of supporting bone around implants. Chronic periodontitis is a risk indicator for implant failure. Both diseases have a common etiology regarding inflammatory destructive response. BRINP3 gene is associated with aggressive periodontitis. However, is still unclear if chronic periodontitis and peri-implantitis have the same genetic background. The aim of this work was to investigate the association between BRINP3 genetic variation (rs1342913 and rs1935881) and expression and susceptibility to both diseases. Methods: Periodontal and peri-implant examinations were performed in 215 subjects, divided into: healthy (without chronic periodontitis and peri-implantitis, n = 93); diseased (with chronic periodontitis and peri-implantitis, n = 52); chronic periodontitis only (n = 36), and peri-implantitis only (n = 34). A replication sample of 92 subjects who lost implants and 185 subjects successfully treated with implants were tested. DNA was extracted from buccal cells. Two genetic markers of BRINP3 (rs1342913 and rs1935881) were genotyped using TaqMan chemistry. Chi-square (p<0.05) compared genotype and allele frequency between groups. A subset of subjects (n = 31) had gingival biopsies harvested. The BRINP3 mRNA levels were studied by CT method (2δδCT). Mann-Whitney test correlated the levels of BRINP3 in each group (p<0.05). Results: Statistically significant association between BRINP3 rs1342913 and peri-implantitis was found in both studied groups (p<0.04). The levels of BRINP3 mRNA were significantly higher in diseased subjects compared to healthy individuals (p<0.01). Conclusion: This study provides evidence that the BRINP3 polymorphic variant rs1342913 and low level of BRINP3 expression are associated with peri-implantitis, independently from the presence of chronic periodontitis.
date: 2015-12-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29394/1/art%253A10.1186%252Fs12903-015-0018-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29394/7/licence.txt
identifier:   Casado, PL and Aguiar, DP and Costa, LC and Fonseca, MA and Vieira, TCS and Alvim-Pereira, CCK and Alvim-Pereira, F and Deeley, K and Granjeiro, JM and Trevilatto, PC and Vieira, AR  (2015) Different contribution of BRINP3 gene in chronic periodontitis and peri-implantitis: A cross-sectional study.  BMC Oral Health, 15 (1).       
relation: 10.1186/s12903-015-0018-6

relation: http://d-scholarship-dev.library.pitt.edu/29224/
title: Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high fat diet
creator: Quintana, MT
creator: He, J
creator: Sullivan, J
creator: Grevengoed, T
creator: Schisler, J
creator: Han, Y
creator: Hill, JA
creator: Yates, CC
creator: Stansfield, WE
creator: Mapanga, RF
creator: Essop, MF
creator: Muehlbauer, MJ
creator: Newgard, CB
creator: Bain, JR
creator: Willis, MS
description: Background: The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipocytes, post-translational modification of PPARs have been identified, including ligand-dependent degradation of PPARs by specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes and heart have not previously been identified. We recently identified that muscle ring finger-1 (MuRF1) and MuRF2 differentially inhibit PPAR activities by mono-ubiquitination, leading to the hypothesis that MuRF3 may regulate PPAR activity in vivo to regulate DCM. Methods: MuRF3-/- mice were challenged with 26 weeks 60 % high fat diet to induce insulin resistance and DCM. Conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1 activities were assayed. Results: MuRF3-/- mice exhibited a premature systolic heart failure by 6 weeks high fat diet (vs. 12 weeks in MuRF3+/+). MuRF3-/- mice weighed significantly less than sibling-matched wildtype mice after 26 weeks HFD. These differences may be largely due to resistance to fat accumulation, as MRI analysis revealed MuRF3-/- mice had significantly less fat mass, but not lean body mass. In vitro ubiquitination assays identified MuRF3 mono-ubiquitinated PPARα and PPARγ1, but not PPARβ. Conclusions: These findings suggest that MuRF3 helps stabilize cardiac PPARα and PPARγ1 in vivo to support resistance to the development of DCM. MuRF3 also plays an unexpected role in regulating fat storage despite being found only in striated muscle.
date: 2015-12-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29224/1/art%253A10.1186%252Fs12902-015-0028-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29224/7/licence.txt
identifier:   Quintana, MT and He, J and Sullivan, J and Grevengoed, T and Schisler, J and Han, Y and Hill, JA and Yates, CC and Stansfield, WE and Mapanga, RF and Essop, MF and Muehlbauer, MJ and Newgard, CB and Bain, JR and Willis, MS  (2015) Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high fat diet.  BMC Endocrine Disorders, 15 (1).       
relation: 10.1186/s12902-015-0028-z

relation: http://d-scholarship-dev.library.pitt.edu/29389/
title: dbVOR: A database system for importing pedigree, phenotype and genotype data and exporting selected subsets
creator: Baron, RV
creator: Conley, YP
creator: Gorin, MB
creator: Weeks, DE
description: Background: When studying the genetics of a human trait, we typically have to manage both genome-wide and targeted genotype data. There can be overlap of both people and markers from different genotyping experiments; the overlap can introduce several kinds of problems. Most times the overlapping genotypes are the same, but sometimes they are different. Occasionally, the lab will return genotypes using a different allele labeling scheme (for example 1/2 vs A/C). Sometimes, the genotype for a person/marker index is unreliable or missing. Further, over time some markers are merged and bad samples are re-run under a different sample name. We need a consistent picture of the subset of data we have chosen to work with even though there might possibly be conflicting measurements from multiple data sources. Results: We have developed the dbVOR database, which is designed to hold data efficiently for both genome-wide and targeted experiments. The data are indexed for fast retrieval by person and marker. In addition, we store pedigree and phenotype data for our subjects. The dbVOR database allows us to select subsets of the data by several different criteria and to merge their results into a coherent and consistent whole. Data may be filtered by: family, person, trait value, markers, chromosomes, and chromosome ranges. The results can be presented in columnar, Mega2, or PLINK format. Conclusions: dbVOR serves our needs well. It is freely available from https://watson.hgen.pitt.edu/register . Documentation for dbVOR can be found at https://watson.hgen.pitt.edu/register/docs/dbvor.html .
date: 2015-12-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29389/1/art%253A10.1186%252Fs12859-015-0505-4.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29389/7/licence.txt
identifier:   Baron, RV and Conley, YP and Gorin, MB and Weeks, DE  (2015) dbVOR: A database system for importing pedigree, phenotype and genotype data and exporting selected subsets.  BMC Bioinformatics, 16 (1).       
relation: 10.1186/s12859-015-0505-4

relation: http://d-scholarship-dev.library.pitt.edu/29380/
title: The impact of pediatric blood and marrow transplant on parents: Introduction of the parent impact scale
creator: Heinze, KE
creator: Rodday, AM
creator: Nolan, MT
creator: Bingen, K
creator: Kupst, MJ
creator: Patel, SK
creator: Syrjala, K
creator: Harris, L
creator: Recklitis, C
creator: Schwartz, L
creator: Davies, S
creator: Guinan, EC
creator: Noll, R
creator: Chang, G
creator: Parsons, SK
description: Background: Parents often experience stress-related complications when their child requires blood and marrow transplant (BMT). Previous studies have described the emotional toll BMT places on parents during the acute phase of care and within the context of clinical complications. In this paper we introduce the Parent Impact Scale (PARimpact), designed to capture physical and emotional challenges of the child's health on the parent. The primary aim of this paper is to examine psychometric properties of PARimpact, and the secondary aim is to explore factors associated with PARimpact scores for further hypothesis generation. Methods: This analysis used a merged dataset of two longitudinal studies. Accompanying parents (n = 363) of children undergoing BMT were surveyed up to six times from pre-BMT baseline to one year after their child's BMT. For this analysis, pre-BMT baseline responses to PARimpact were used to examine the factor structure with Principal Component Analysis (PCA) and Exploratory Factor Analysis (EFA). Construct validity was assessed, and multivariable regression was used to examine relationships between PARimpact and BMT clinical variables. Results: PCA and EFA revealed a one-factor solution with acceptable item loading; Cronbach's aα was 0.83 at baseline. Hypothesized differences in known groups were detected for BMT complications with significantly higher PARimpact scores for those with vs. without each complication. In the adjusted multivariable regression models, acute graft versus host disease (b = 5.3; p = 0.03), end organ toxicity (b = 5.9; p < 0.01), and systemic infection (b = 9.1; p < 0.01) were associated with significantly higher mean PARimpact scores in the first 3 months following transplant. After the first 3 months to 1 year post BMT, systemic infection was associated with increased mean PARimpact scores (b = 19.2; p < 0.01). Conclusions: Initial results suggest that the PARimpact is valid and reliable. Our finding that clinical complications increase the impact of BMT on the caretaking parent indicates the need for BMT healthcare professionals to identify these events and help parents navigate the BMT course. Clinical application of the PARimpact scale should be considered to identify high-risk families and provide targeted interventions to augment care.
date: 2015-12-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29380/1/art%253A10.1186%252Fs12955-015-0240-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29380/7/licence.txt
identifier:   Heinze, KE and Rodday, AM and Nolan, MT and Bingen, K and Kupst, MJ and Patel, SK and Syrjala, K and Harris, L and Recklitis, C and Schwartz, L and Davies, S and Guinan, EC and Noll, R and Chang, G and Parsons, SK  (2015) The impact of pediatric blood and marrow transplant on parents: Introduction of the parent impact scale.  Health and Quality of Life Outcomes, 13 (1).       
relation: 10.1186/s12955-015-0240-6

relation: http://d-scholarship-dev.library.pitt.edu/28940/
title: LENS: Web-based lens for enrichment and network studies of human proteins
creator: Handen, A
creator: Ganapathiraju, MK
description: Background: Network analysis is a common approach for the study of genetic view of diseases and biological pathways. Typically, when a set of genes are identified to be of interest in relation to a disease, say through a genome wide association study (GWAS) or a different gene expression study, these genes are typically analyzed in the context of their protein-protein interaction (PPI) networks. Further analysis is carried out to compute the enrichment of known pathways and disease-associations in the network. Having tools for such analysis at the fingertips of biologists without the requirement for computer programming or curation of data would accelerate the characterization of genes of interest. Currently available tools do not integrate network and enrichment analysis and their visualizations, and most of them present results in formats not most conducive to human cognition. Results: We developed the tool Lens for Enrichment and Network Studies of human proteins (LENS) that performs network and pathway and diseases enrichment analyses on genes of interest to users. The tool creates a visualization of the network, provides easy to read statistics on network connectivity, and displays Venn diagrams with statistical significance values of the network's association with drugs, diseases, pathways, and GWASs. We used the tool to analyze gene sets related to craniofacial development, autism, and schizophrenia. Conclusion: LENS is a web-based tool that does not require and download or plugins to use. The tool is free and does not require login for use, and is available at http://severus.dbmi.pitt.edu/LENS.
date: 2015-12-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28940/1/art%253A10.1186%252F1755-8794-8-S4-S2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28940/7/licence.txt
identifier:   Handen, A and Ganapathiraju, MK  (2015) LENS: Web-based lens for enrichment and network studies of human proteins.  BMC Medical Genomics, 8 (4).       
relation: 10.1186/1755-8794-8-S4-S2

relation: http://d-scholarship-dev.library.pitt.edu/28941/
title: Examining systemic steroid Use in older inflammatory bowel disease patients using hurdle models: A cohort study
creator: Johnson, SL
creator: Palta, M
creator: Bartels, CM
creator: Thorpe, CT
creator: Weiss, JM
creator: Smith, MA
description: Background: Interpreting clinical guideline adherence and the appropriateness of medication regimens requires consideration of individual patient and caregiver factors. Factors leading to initiation of a medication may differ from those determining continued use. We believe this is the case for systemic steroid therapy in inflammatory bowel disease (IBD), resulting in a need to apply methods that separately consider factors associated with initiation and duration of therapy. To evaluate the relationship between patient characteristics and the frequency and duration of incident steroid use we apply a 2-part hurdle model to Medicare data. We do so in older patients with tumor necrosis factor antagonist (anti-TNFs) contraindications, as they are of special interest for compliance with Medicare-adopted, quality metrics calling for anti-TNFs and nonbiologic immune therapies to reduce steroid utilization. Many older patients have contraindications to anti-TNFs. However, nonbiologics cause adverse events that are concerning in older adults, limiting their use in this population and increasing reliance on systemic steroids. Methods: We used a national Medicare sample for 2006-2009 including patients with 12months or greater of Parts A and B and 6months or greater of Part D coverage, IBD confirmed with at least 2 claims for ICD-9CM 555.xx or 556.xx, anti-TNF contraindications and without contraindications to nonbiologic agents. We applied a negative binomial-logit hurdle model to examine patient characteristics associated with systemic steroid utilization. Results: Among the 1,216 IBD patients without baseline steroid use, 21% used systemic steroids. Odds of receiving systemic steroids were greater in those younger, rural, and those receiving other agents. Available patient characteristics failed to predict longer steroid treatment duration. Conclusions: Our study identified differences in predictors of frequency and duration of medication use and suggests the utility of two-part models to examine drug utilization patterns. Applying such a model to Medicare data, we determined that despite medical consensus that systemic steroid use should be minimized, its use was substantial. Findings indicate anticipated difficulties in implementing recently adopted quality measures to avoid systemic steroids.
date: 2015-12-08
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28941/1/art%253A10.1186%252Fs40360-015-0034-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28941/7/licence.txt
identifier:   Johnson, SL and Palta, M and Bartels, CM and Thorpe, CT and Weiss, JM and Smith, MA  (2015) Examining systemic steroid Use in older inflammatory bowel disease patients using hurdle models: A cohort study.  BMC Pharmacology and Toxicology, 16 (1).   ISSN 2050-6511     
relation: 10.1186/s40360-015-0034-9

relation: http://d-scholarship-dev.library.pitt.edu/28943/
title: Automated parameter estimation for biological models using Bayesian statistical model checking
creator: Hussain, F
creator: Langmead, CJ
creator: Mi, Q
creator: Dutta-Moscato, J
creator: Vodovotz, Y
creator: Jha, SK
description: Background: Probabilistic models have gained widespread acceptance in the systems biology community as a useful way to represent complex biological systems. Such models are developed using existing knowledge of the structure and dynamics of the system, experimental observations, and inferences drawn from statistical analysis of empirical data. A key bottleneck in building such models is that some system variables cannot be measured experimentally. These variables are incorporated into the model as numerical parameters. Determining values of these parameters that justify existing experiments and provide reliable predictions when model simulations are performed is a key research problem. Domain experts usually estimate the values of these parameters by fitting the model to experimental data. Model fitting is usually expressed as an optimization problem that requires minimizing a cost-function which measures some notion of distance between the model and the data. This optimization problem is often solved by combining local and global search methods that tend to perform well for the specific application domain. When some prior information about parameters is available, methods such as Bayesian inference are commonly used for parameter learning. Choosing the appropriate parameter search technique requires detailed domain knowledge and insight into the underlying system. Results: Using an agent-based model of the dynamics of acute inflammation, we demonstrate a novel parameter estimation algorithm by discovering the amount and schedule of doses of bacterial lipopolysaccharide that guarantee a set of observed clinical outcomes with high probability. We synthesized values of twenty-eight unknown parameters such that the parameterized model instantiated with these parameter values satisfies four specifications describing the dynamic behavior of the model. Conclusions: We have developed a new algorithmic technique for discovering parameters in complex stochastic models of biological systems given behavioral specifications written in a formal mathematical logic. Our algorithm uses Bayesian model checking, sequential hypothesis testing, and stochastic optimization to automatically synthesize parameters of probabilistic biological models.
date: 2015-12-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28943/1/art%253A10.1186%252F1471-2105-16-S17-S8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28943/7/licence.txt
identifier:   Hussain, F and Langmead, CJ and Mi, Q and Dutta-Moscato, J and Vodovotz, Y and Jha, SK  (2015) Automated parameter estimation for biological models using Bayesian statistical model checking.  BMC Bioinformatics, 16 (17).       
relation: 10.1186/1471-2105-16-S17-S8

relation: http://d-scholarship-dev.library.pitt.edu/26387/
title: An Effective Algorithm for Computing All-terminal Reliability Bounds
creator: Silva, Jaime
creator: Gomes, Teresa
creator: Tipper, David
creator: Martins, Lucia
creator: Kounev, Velin
description: The exact calculation of all-terminal reliability is not feasible in large networks. Hence estimation techniques and lower and upper bounds for all-terminal reliability have been utilized. Here, we propose using an ordered subset of the mincuts and an ordered subset of the minpaths to calculate an all-terminal reliability upper and lower bound, respectively. The advantage of the proposed new approach results from the fact that it does not require the enumeration of all mincuts or all minpaths as required by other bounds. The proposed algorithm uses maximally disjoint minpaths, prior to their sequential generation, and also uses a binary decision diagram for the calculation of their union probability. The numerical results show that the proposed approach is computationally feasible, reasonably accurate and much faster than the previous version of the algorithm. This allows one to obtain tight bounds when it not possible to enumerate all mincuts or all minpaths as revealed by extensive tests on real-world networks.
publisher: Wiley
date: 2015-12-05
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26387/1/licence.txt
identifier:   Silva, Jaime and Gomes, Teresa and Tipper, David and Martins, Lucia and Kounev, Velin  (2015) An Effective Algorithm for Computing All-terminal Reliability Bounds.  Networks, 66 (4).  282 - 295.      
relation: 10.1002/net

relation: http://d-scholarship-dev.library.pitt.edu/32679/
title: A Muscle Synergy-Inspired Adaptive Control Scheme for a Hybrid Walking Neuroprosthesis.
creator: Alibeji, Naji A
creator: Kirsch, Nicholas Andrew
creator: Sharma, Nitin
description: A hybrid neuroprosthesis that uses an electric motor-based wearable exoskeleton and functional electrical stimulation (FES) has a promising potential to restore walking in persons with paraplegia. A hybrid actuation structure introduces effector redundancy, making its automatic control a challenging task because multiple muscles and additional electric motor need to be coordinated. Inspired by the muscle synergy principle, we designed a low dimensional controller to control multiple effectors: FES of multiple muscles and electric motors. The resulting control system may be less complex and easier to control. To obtain the muscle synergy-inspired low dimensional control, a subject-specific gait model was optimized to compute optimal control signals for the multiple effectors. The optimal control signals were then dimensionally reduced by using principal component analysis to extract synergies. Then, an adaptive feedforward controller with an update law for the synergy activation was designed. In addition, feedback control was used to provide stability and robustness to the control design. The adaptive-feedforward and feedback control structure makes the low dimensional controller more robust to disturbances and variations in the model parameters and may help to compensate for other time-varying phenomena (e.g., muscle fatigue). This is proven by using a Lyapunov stability analysis, which yielded semi-global uniformly ultimately bounded tracking. Computer simulations were performed to test the new controller on a 4-degree of freedom gait model.
date: 2015-12-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32679/1/fbioe-03-00203.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32679/7/licence.txt
identifier:   Alibeji, Naji A and Kirsch, Nicholas Andrew and Sharma, Nitin  (2015) A Muscle Synergy-Inspired Adaptive Control Scheme for a Hybrid Walking Neuroprosthesis.  Front Bioeng Biotechnol, 3.  203 - ?.  ISSN 2296-4185     
relation: 10.3389/fbioe.2015.00203
language: eng

relation: http://d-scholarship-dev.library.pitt.edu/28946/
title: Determinants of patient preferences for total knee replacement: African-Americans and whites
creator: Kwoh, CK
creator: Vina, ER
creator: Cloonan, YK
creator: Hannon, MJ
creator: Boudreau, RM
creator: Ibrahim, SA
description: Introduction: Patient preferences contribute to marked racial disparities in the utilization of total knee replacement (TKR). The objectives of this study were to identify the determinants of knee osteoarthritis (OA) patients' preferences regarding TKR by race and to identify the variables that may mediate racial differences in willingness to undergo TKR. Methods: Five hundred fourteen White (WH) and 285 African-American (AA) patients with chronic knee pain and radiographic evidence of OA participated in the study. Participants were recruited from the community, an academic medical center, and a Veterans Affairs hospital. Structured interviews were conducted to collect socio-demographics, disease severity, socio-cultural determinants, and treatment preferences. Logistic regression was performed, stratified by race, to identify determinants of preferences. Clinical and socio-cultural factors were entered simultaneously into the models. Stepwise selection identified factors for inclusion in the final models (p < 0.20). Results: Compared to WHs, AAs were less willing to undergo TKR (80% vs. 62%, respectively). Better expectations regarding TKR surgery outcomes determined willingness to undergo surgery in both AAs (odds ratio (OR) 2.08, 95% confidence interval (CI) 0.91-4.79 for 4th vs. 1st quartile) and WHs (OR 5.11, 95% CI 2.31-11.30 for 4th vs. 1st quartile). Among AAs, better understanding of the procedure (OR 1.80, 95% CI 0.97-3.35), perceiving a short hospital course (OR 0.81, 95% CI 0.58-1.13), and believing in less post-surgical pain (OR 0.73, 95% CI 0.39-1.35) and walking difficulties (OR 0.66, 95% CI 0.37-1.16) also determined willingness. Among WHs, having surgical discussion with a physician (OR 1.96, 95% CI 1.05-3.68), not ever receiving surgical referral (OR 0.56, 95% CI 0.32-0.99), and higher trust in the healthcare system (OR 1.58, 95% CI 0.75-3.31 for 4th vs. 1st quartile) additionally determined willingness. Among the variables considered, only knowledge-related matters pertaining to TKR attenuated the racial difference in knee OA patients' treatment preference. Conclusions: Expectations of surgical outcomes influence preference for TKR in all patients, but clinical and socio-cultural factors exist that shape marked racial differences in preferences for TKR. Interventions to reduce or eliminate racial disparities in the utilization of TKR should consider and target these factors.
date: 2015-12-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28946/1/art%253A10.1186%252Fs13075-015-0864-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28946/7/licence.txt
identifier:   Kwoh, CK and Vina, ER and Cloonan, YK and Hannon, MJ and Boudreau, RM and Ibrahim, SA  (2015) Determinants of patient preferences for total knee replacement: African-Americans and whites.  Arthritis Research and Therapy, 17 (1).   ISSN 1478-6354     
relation: 10.1186/s13075-015-0864-2

relation: http://d-scholarship-dev.library.pitt.edu/28347/
title: Aquaporin 5 interacts with fluoride and possibly protects against caries
creator: Anjomshoaa, I
creator: Briseño-Ruiz, J
creator: Deeley, K
creator: Poletta, FA
creator: Mereb, JC
creator: Leite, AL
creator: Barreta, PATM
creator: Silva, TL
creator: Dizak, P
creator: Ruff, T
creator: Patir, A
creator: Koruyucu, M
creator: Abbasoglu, Z
creator: Casado, PL
creator: Brown, A
creator: Zaky, SH
creator: Bayram, M
creator: Küchler, EC
creator: Cooper, ME
creator: Liu, K
creator: Marazita, ML
creator: Tanboga, I
creator: Granjeiro, JM
creator: Seymen, F
creator: Castilla, EE
creator: Orioli, IM
creator: Sfeir, C
creator: Owyang, H
creator: Buzalaf, MAR
creator: Vieira, AR
description: Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28347/1/journal.pone.0143068.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28347/3/licence.txt
identifier:   Anjomshoaa, I and Briseño-Ruiz, J and Deeley, K and Poletta, FA and Mereb, JC and Leite, AL and Barreta, PATM and Silva, TL and Dizak, P and Ruff, T and Patir, A and Koruyucu, M and Abbasoglu, Z and Casado, PL and Brown, A and Zaky, SH and Bayram, M and Küchler, EC and Cooper, ME and Liu, K and Marazita, ML and Tanboga, I and Granjeiro, JM and Seymen, F and Castilla, EE and Orioli, IM and Sfeir, C and Owyang, H and Buzalaf, MAR and Vieira, AR  (2015) Aquaporin 5 interacts with fluoride and possibly protects against caries.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0143068

relation: http://d-scholarship-dev.library.pitt.edu/28348/
title: Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?
creator: Mitsuishi, Sumie
creator: Nishimura, Rimei
creator: Ando, Kiyotaka
creator: Tsujino, Daisuke
creator: Utsunomiya, Kazunori
contributor: Atkin, Stephen L
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28348/1/journal.pone.0144041.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28348/3/licence.txt
identifier:   Mitsuishi, Sumie and Nishimura, Rimei and Ando, Kiyotaka and Tsujino, Daisuke and Utsunomiya, Kazunori  (2015) Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?  PLOS ONE, 10 (12).  e0144041 - e0144041.      
relation: 10.1371/journal.pone.0144041

relation: http://d-scholarship-dev.library.pitt.edu/28323/
title: Clinical implications of having reduced mid forced expiratory flow rates (FEF<inf>25-75</inf>), independently of FEV1, in adult patients with asthma
creator: Riley, CM
creator: Wenzel, SE
creator: Castro, M
creator: Erzurum, SC
creator: Chung, KF
creator: Fitzpatrick, AM
creator: Gaston, B
creator: Israel, E
creator: Moore, WC
creator: Bleecker, ER
creator: Calhoun, WJ
creator: Jarjour, NN
creator: Busse, WW
creator: Peters, SP
creator: Teague, WG
creator: Sorkness, R
creator: Holguin, F
description: Introduction: FEF25-75 is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV1 or the FEV1/FVC ratio. Purpose: To determine the association between Hankinson's percent-predicted FEF25-75 (FEF25-75%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation. Methods: In participants enrolled in the Severe Asthma Research Program 1-2, we compared outcomes across FEF25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV1, and the FEV1/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF25-75% below the lower limit of normal (LLN) and FEV1/FVC above LLN. Results: Subjects in the lowest FEF25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF25-75% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3-6.9]), persistent symptoms (OR 3.3 [95%CI 1-11], ICU admission for asthma (3.7 [1.3-10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF25-75% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness. Conclusions: After controlling for demographic variables, FEV1 and FEV1/FVC, a reduced FEF25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF25-75% is an independent biomarker for more severe asthma.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28323/1/journal.pone.0145476.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28323/3/licence.txt
identifier:   Riley, CM and Wenzel, SE and Castro, M and Erzurum, SC and Chung, KF and Fitzpatrick, AM and Gaston, B and Israel, E and Moore, WC and Bleecker, ER and Calhoun, WJ and Jarjour, NN and Busse, WW and Peters, SP and Teague, WG and Sorkness, R and Holguin, F  (2015) Clinical implications of having reduced mid forced expiratory flow rates (FEF<inf>25-75</inf>), independently of FEV1, in adult patients with asthma.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0145476

relation: http://d-scholarship-dev.library.pitt.edu/27216/
title: En el corazón de la modernidad: nihilismo en La vorágine de José Eustasio Rivera
creator: Sanchez Lopera, Alejandro
description: Este ensayo se distancia de las interpretaciones que presentan La vorágine de José Eustasio Rivera como novela de la tierra, o como síntoma del arcaísmo de la periferia. Sostengo que la novela de Rivera, lejos de inscribirse en las expresiones telúricas de la “novela terrígena,” o en los despotismos de lo arcaico al margen de lo civil, lo hace en los nervios de la experiencia moderna misma. Por ende, la vida de su personaje central, Arturo Cova, es el recorrido de la consumación del nihilismo.
publisher: University of SanDiego
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27216/1/1_La_Voragine_Jose_Eustasio_Rivera__Estudios_Colombianos.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27216/4/licence.txt
identifier:   Sanchez Lopera, Alejandro  (2015) En el corazón de la modernidad: nihilismo en La vorágine de José Eustasio Rivera.  Revista de Estudios Colombianos (46).  16 - 24.  ISSN 0121-2117     

relation: http://d-scholarship-dev.library.pitt.edu/28332/
title: Genomic epidemiology of an endoscope-associated outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae
creator: Marsh, JW
creator: Krauland, MG
creator: Nelson, JS
creator: Schlackman, JL
creator: Brooks, AM
creator: Pasculle, AW
creator: Shutt, KA
creator: Doi, Y
creator: Querry, AM
creator: Muto, CA
creator: Harrison, LH
description: Increased incidence of infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) was noted among patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) at a single hospital. An epidemiologic investigation identified KPC-Kp and non-KPC-producing, extended-spectrum β-lactamase (ESBL)-producing Kp in cultures from 2 endoscopes. Genotyping was performed on patient and endoscope isolates to characterize the microbial genomics of the outbreak. Genetic similarity of 51 Kp isolates from 37 patients and 3 endoscopes was assessed by pulsedfield gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Five patient and 2 endoscope isolates underwent whole genome sequencing (WGS). Two KPC-encoding plasmids were characterized by single molecule, real-time sequencing. Plasmid diversity was assessed by endonuclease digestion. Genomic and epidemiologic data were used in conjunction to investigate the outbreak source. Two clusters of Kp patient isolates were genetically related to endoscope isolates by PFGE. A subset of patient isolates were collected post-ERCP, suggesting ERCP endoscopes as a possible source. A phylogeny of 7 Kp genomes from patient and endoscope isolates supported ERCP as a potential source of transmission. Differences in gene content defined 5 ST258 subclades and identified 2 of the subclades as outbreak-associated. A novel KPC-encoding plasmid, pKp28 helped define and track one endoscope-associated ST258 subclade. WGS demonstrated high genetic relatedness of patient and ERCP endoscope isolates suggesting ERCP-associated transmission of ST258 KPC-Kp. Gene and plasmid content discriminated the outbreak from endemic ST258 populations and assisted with the molecular epidemiologic investigation of an extended KPC-Kp outbreak.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28332/1/journal.pone.0144310.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28332/3/licence.txt
identifier:   Marsh, JW and Krauland, MG and Nelson, JS and Schlackman, JL and Brooks, AM and Pasculle, AW and Shutt, KA and Doi, Y and Querry, AM and Muto, CA and Harrison, LH  (2015) Genomic epidemiology of an endoscope-associated outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0144310

relation: http://d-scholarship-dev.library.pitt.edu/28349/
title: Learning predictive interactions using information gain and Bayesian network scoring
creator: Jiang, X
creator: Jao, J
creator: Neapolitan, R
description: Background The problems of correlation and classification are long-standing in the fields of statistics and machine learning, and techniques have been developed to address these problems. We are now in the era of high-dimensional data, which is data that can concern billions of variables. These data present new challenges. In particular, it is difficult to discover predictive variables, when each variable has little marginal effect. An example concerns Genomewide Association Studies (GWAS) datasets, which involve millions of single nucleotide polymorphism (SNPs), where some of the SNPs interact epistatically to affect disease status. Towards determining these interacting SNPs, researchers developed techniques that addressed this specific problem. However, the problem is more general, and so these techniques are applicable to other problems concerning interactions. A difficulty with many of these techniques is that they do not distinguish whether a learned interaction is actually an interaction or whether it involves several variables with strong marginal effects. Methodology/Findings We address this problem using information gain and Bayesian network scoring. First, we identify candidate interactions by determining whether together variables provide more information than they do separately. Then we use Bayesian network scoring to see if a candidate interaction really is a likely model. Our strategy is called MBS-IGain. Using 100 simulated datasets and a real GWAS Alzheimer's dataset, we investigated the performance of MBS-IGain. Conclusions/Significance When analyzing the simulated datasets, MBS-IGain substantially out-performed nine previous methods at locating interacting predictors, and at identifying interactions exactly. When analyzing the real Alzheimer's dataset, we obtained new results and results that substantiated previous findings. We conclude that MBS-IGain is highly effective at finding interactions in high-dimensional datasets. This result is significant because we have increasingly abundant high-dimensional data in many domains, and to learn causes andperform prediction/classification using these data, we often must first identify interactions.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28349/1/journal.pone.0143247.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28349/3/licence.txt
identifier:   Jiang, X and Jao, J and Neapolitan, R  (2015) Learning predictive interactions using information gain and Bayesian network scoring.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0143247

relation: http://d-scholarship-dev.library.pitt.edu/28341/
title: Neutrophil gelatinase associated lipocalin (NGAL) in leptospirosis acute kidney injury: A multicenter study in Thailand
creator: Srisawat, N
creator: Praditpornsilpa, K
creator: Patarakul, K
creator: Techapornrung, M
creator: Daraswang, T
creator: Sukmark, T
creator: Khositrangsikun, K
creator: Fakthongyoo, A
creator: Oranrigsupak, P
creator: Praderm, L
creator: Suwattanasilpa, U
creator: Peerapornratana, S
creator: Loahaveeravat, P
creator: Suwachittanont, N
creator: Wirotwan, TO
creator: Phonork, C
creator: Kumpunya, S
creator: Tiranathanagul, K
creator: Chirathaworn, C
creator: Eiam-Ong, S
creator: Tungsanga, K
creator: Sitprija, V
creator: Kellum, JA
creator: Townamchai, N
description: AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28341/1/journal.pone.0143367.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28341/3/licence.txt
identifier:   Srisawat, N and Praditpornsilpa, K and Patarakul, K and Techapornrung, M and Daraswang, T and Sukmark, T and Khositrangsikun, K and Fakthongyoo, A and Oranrigsupak, P and Praderm, L and Suwattanasilpa, U and Peerapornratana, S and Loahaveeravat, P and Suwachittanont, N and Wirotwan, TO and Phonork, C and Kumpunya, S and Tiranathanagul, K and Chirathaworn, C and Eiam-Ong, S and Tungsanga, K and Sitprija, V and Kellum, JA and Townamchai, N  (2015) Neutrophil gelatinase associated lipocalin (NGAL) in leptospirosis acute kidney injury: A multicenter study in Thailand.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0143367

relation: http://d-scholarship-dev.library.pitt.edu/29279/
title: Novel approaches in the management of pancreatic ductal adenocarcinoma: Potential promises for the future
creator: Goel, G
creator: Sun, W
description: Abstract Despite a few breakthroughs in therapy for advanced disease in the recent years, pancreatic ductal adenocarcinoma continues to remain one of the most challenging human malignancies to treat. The overall prognosis for the majority of patients with pancreatic cancer is rather dismal, and therefore, more effective treatment options are being desperately sought. The practical goals of management are to improve the cure rates for patients with resectable disease, achieve a higher conversion rate of locally advanced tumor into potentially resectable disease, and finally, prolong the overall survival for those who develop metastatic disease. Our understanding of the complex genetic alterations, the implicated molecular pathways, and the role of desmoplastic stroma in pancreatic cancer tumorigenesis has increased several folds in the recent years. This has facilitated the development of novel therapeutic strategies against pancreatic cancer, some of which are currently under evaluation in ongoing preclinical and clinical studies. This review will summarize the existing treatment approaches for this devastating disease and also discuss the promising therapeutic approaches that are currently in different stages of clinical development.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29279/1/art%253A10.1186%252Fs13045-015-0141-5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29279/7/licence.txt
identifier:   Goel, G and Sun, W  (2015) Novel approaches in the management of pancreatic ductal adenocarcinoma: Potential promises for the future.  Journal of Hematology and Oncology, 8 (1).       
relation: 10.1186/s13045-015-0141-5

relation: http://d-scholarship-dev.library.pitt.edu/28947/
title: Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis
creator: Baker, N
creator: Sohn, J
creator: Tuan, RS
description: Introduction: Stem cells are considered an important resource for tissue repair and regeneration. Their utilization in regenerative medicine will be aided by mechanistic insight into their responsiveness to external stimuli. It is likely that, similar to all other cells, an initial determinant of stem cell responsiveness to external stimuli is the organization of signaling molecules in cell membrane rafts. The clustering of signaling molecules in these cholesterol-rich membrane microdomains can affect the activity, specificity, cross-talk and amplification of cell signaling. Membrane rafts fall into two broad categories, non-caveolar and caveolar, based on the absence or presence, respectively, of caveolin scaffolding proteins. We have recently demonstrated that caveolin-1 (Cav-1) expression increases during, and knockdown of Cav-1 expression enhances, osteogenic differentiation of human bone marrow derived mesenchymal stem cells (MSCs). The increase in Cav-1 expression observed during osteogenesis is likely a negative feedback mechanism. We hypothesize that focal adhesion signaling pathways such as PI3K/Akt signaling may be negatively regulated by Cav-1 during human MSC osteogenesis. Methods: Human bone marrow MSCs were isolated from femoral heads obtained after total hip arthroplasty. MSCs were incubated in standard growth medium alone or induced to osteogenically differentiate by the addition of supplements (β-glycerophosphate, ascorbic acid, dexamethasone, and 1,25-dihydroxyvitamin D3). The activation of and requirement for PI3K/Akt signaling in MSC osteogenesis were assessed by immunoblotting for phosphorylated Akt, and treatment with the PI3K inhibitor LY294002 and Akt siRNA, respectively. The influences of Cav-1 and cholesterol membrane rafts on PI3K/Akt signaling were investigated by treatment with Cav-1 siRNA, methyl-β-cyclodextrin, or cholesterol oxidase, followed by cellular sub-fractionation and/or immunoblotting for phosphorylated Akt. Results: LY294002 and Akt siRNA inhibited MSC osteogenesis. Methyl-β-cyclodextrin, which disrupts all membrane rafts, inhibited osteogenesis. Conversely, Cav-1 siRNA and cholesterol oxidase, which displaces Cav-1 from caveolae, enhanced Akt signaling induced by osteogenic supplements. In control cells, phosphorylated Akt began to accumulate in caveolae after 10 days of osteogenic differentiation. Conclusions: PI3K/Akt signaling is a key pathway required for human MSC osteogenesis, and it is likely that localization of active Akt in non-caveolar and caveolar membrane rafts positively and negatively contributes to osteogenesis, respectively.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28947/1/art%253A10.1186%252Fs13287-015-0225-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28947/7/licence.txt
identifier:   Baker, N and Sohn, J and Tuan, RS  (2015) Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis.  Stem Cell Research and Therapy, 6 (1).       
relation: 10.1186/s13287-015-0225-8

relation: http://d-scholarship-dev.library.pitt.edu/28324/
title: Proportional topology optimization: A new non-sensitivity method for solving stress constrained and minimum compliance problems and its implementation in MATLAB
creator: Biyikli, E
creator: To, AC
description: A new topology optimization method called the Proportional Topology Optimization (PTO) is presented. As a non-sensitivity method, PTO is simple to understand, easy to implement, and is also efficient and accurate at the same time. It is implemented into two MATLAB programs to solve the stress constrained and minimum compliance problems. Descriptions of the algorithm and computer programs are provided in detail. The method is applied to solve three numerical examples for both types of problems. The method shows comparable efficiency and accuracy with an existing optimality criteria method which computes sensitivities. Also, the PTO stress constrained algorithm and minimum compliance algorithm are compared by feeding output from one algorithm to the other in an alternative manner, where the former yields lower maximum stress and volume fraction but higher compliance compared to the latter. Advantages and disadvantages of the proposed method and future works are discussed. The computer programs are self-contained and publicly shared in the website www.ptomethod.org.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28324/1/journal.pone.0145041.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28324/3/licence.txt
identifier:   Biyikli, E and To, AC  (2015) Proportional topology optimization: A new non-sensitivity method for solving stress constrained and minimum compliance problems and its implementation in MATLAB.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0145041

relation: http://d-scholarship-dev.library.pitt.edu/28325/
title: Safety of oral amphetamine administered during positron emission tomography scans in medically screened humans
creator: Weidner, LD
creator: Paris, A
creator: Frankle, WG
creator: Narendran, R
description: Changes in endogenous dopamine levels can be detected in humans using positron emission tomography scans by measuring the amount by which a specific D2/3 radioligand is displaced. In some cases, a challenge drug such as amphetamine is introduced to increase the amount of dopamine released into the synaptic cleft. Although intravenous amphetamine is often utilized, oral amphetamine has been shown to be just as effective in increasing endogenous dopamine levels. Based on our own use of oral amphetamine as a challenge drug, we have retroactively reviewed our study charts to determine the cardiovascular safety of 0.5 mg kg-1 oral d-amphetamine. Of 172 amphetamine administrations in 144 individuals, only 2.8% of subjects experienced any transient adverse effects. In addition, we found no clinically relevant differences in increases of vital signs between healthy controls and patients. We therefore reaffirm the safety of 0.5 mg kg-1 oral amphetamine in subjects previously screened for cardiovascular risk factors.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28325/1/journal.pone.0140647.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28325/3/licence.txt
identifier:   Weidner, LD and Paris, A and Frankle, WG and Narendran, R  (2015) Safety of oral amphetamine administered during positron emission tomography scans in medically screened humans.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0140647

relation: http://d-scholarship-dev.library.pitt.edu/28328/
title: Structural and functional brain remodeling during pregnancy with diffusion tensor MRI and resting-state functional MRI
creator: Chan, RW
creator: Ho, LC
creator: Zhou, IY
creator: Gao, PP
creator: Chan, KC
creator: Wu, EX
description: Although pregnancy-induced hormonal changes have been shown to alter the brain at the neuronal level, the exact effects of pregnancy on brain at the tissue level remain unclear. In this study, diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) were employed to investigate and document the effects of pregnancy on the structure and function of the brain tissues. Fifteen Sprague-Dawley female rats were longitudinally studied at three days before mating (baseline) and seventeen days after mating (G17). G17 is equivalent to the early stage of the third trimester in humans. Seven age-matched nulliparous female rats served as non-pregnant controls and were scanned at the same time-points. For DTI, diffusivity was found to generally increase in the whole brain during pregnancy, indicating structural changes at microscopic levels that facilitated water molecular movement. Regionally, mean diffusivity increased more pronouncedly in the dorsal hippocampus while fractional anisotropy in the dorsal dentate gyrus increased significantly during pregnancy. For rsfMRI, bilateral functional connectivity in the hippocampus increased significantly during pregnancy. Moreover, fractional anisotropy increase in the dentate gyrus appeared to correlate with the bilateral functional connectivity increase in the hippocampus. These findings revealed tissue structural modifications in the whole brain during pregnancy, and that the hippocampus was structurally and functionally remodeled in a more marked manner.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28328/1/journal.pone.0144328.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28328/3/licence.txt
identifier:   Chan, RW and Ho, LC and Zhou, IY and Gao, PP and Chan, KC and Wu, EX  (2015) Structural and functional brain remodeling during pregnancy with diffusion tensor MRI and resting-state functional MRI.  PLoS ONE, 10 (12).       
relation: 10.1371/journal.pone.0144328

relation: http://d-scholarship-dev.library.pitt.edu/29201/
title: The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries
creator: Zhou, Y
creator: Zhang, J
creator: Wu, H
creator: Hogan, MCV
creator: Wang, JHC
description: Introduction: Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. Methods: TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. Results: Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III. Conclusions: These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
date: 2015-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29201/1/art%253A10.1186%252Fs13287-015-0172-4.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29201/7/licence.txt
identifier:   Zhou, Y and Zhang, J and Wu, H and Hogan, MCV and Wang, JHC  (2015) The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries.  Stem Cell Research and Therapy, 6 (1).       
relation: 10.1186/s13287-015-0172-4

relation: http://d-scholarship-dev.library.pitt.edu/29188/
title: Alcohol screening a brief intervention: a self-paced program for nurses
creator: Finnell, Deborah
creator: Mitchell, Ann M
creator: Savage, Christine L
creator: Kane, Irene
creator: Kearns, Robert
creator: Poole, Nathan
creator: Rizzo-Busack, Hilda
creator: Coulson, Scott
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29188/1/art%253A10.1186%252F1940-0640-10-S2-O18.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29188/7/licence.txt
identifier:   Finnell, Deborah and Mitchell, Ann M and Savage, Christine L and Kane, Irene and Kearns, Robert and Poole, Nathan and Rizzo-Busack, Hilda and Coulson, Scott  (2015) Alcohol screening a brief intervention: a self-paced program for nurses.  Addiction Science &amp; Clinical Practice, 10 (S2).       
relation: 10.1186/1940-0640-10-s2-o18
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29010/
title: Anti-EGFR mAb cetuximab therapy increases T cell receptor (TCR) diversity in the peripheral blood and focuses TCR richness in the tumor microenvironment
creator: Kansy, Benjamin A
creator: Lin, Yan
creator: Ding, Fei
creator: Gibson, Sandra Poveda
creator: Jie, Hyun-Bae
creator: Ferris, Robert L
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29010/1/art%253A10.1186%252F2051-1426-3-S2-P73.pdf
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rights: attached
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identifier:   Kansy, Benjamin A and Lin, Yan and Ding, Fei and Gibson, Sandra Poveda and Jie, Hyun-Bae and Ferris, Robert L  (2015) Anti-EGFR mAb cetuximab therapy increases T cell receptor (TCR) diversity in the peripheral blood and focuses TCR richness in the tumor microenvironment.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p73
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29018/
title: Anti-EGFR targeted monoclonal antibody isotype influences anti-tumor immunity in head and neck cancer patients
creator: Trivedi, Sumita
creator: Srivastava, Raghvendra M
creator: Concha-Benavente, Fernando
creator: Garcia-Bates, Tatiana M
creator: Li, Jing
creator: Ferris, Robert L
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29018/1/art%253A10.1186%252F2051-1426-3-S2-P316.pdf
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identifier:   Trivedi, Sumita and Srivastava, Raghvendra M and Concha-Benavente, Fernando and Garcia-Bates, Tatiana M and Li, Jing and Ferris, Robert L  (2015) Anti-EGFR targeted monoclonal antibody isotype influences anti-tumor immunity in head and neck cancer patients.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p316
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29017/
title: Anti-PD-1 mAb pre-radiotherapy (RT) loading dose and fractionated RT induce better tumor-specific immunity and tumor shrinkage than sequential administration in an HPV+ head and neck cancer model
creator: Srivastava, Raghvendra M
creator: Clump, David A
creator: Ferris, Robert L
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29017/1/art%253A10.1186%252F2051-1426-3-S2-P314.pdf
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rights: attached
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identifier:   Srivastava, Raghvendra M and Clump, David A and Ferris, Robert L  (2015) Anti-PD-1 mAb pre-radiotherapy (RT) loading dose and fractionated RT induce better tumor-specific immunity and tumor shrinkage than sequential administration in an HPV+ head and neck cancer model.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p314
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29023/
title: Antigen presentation by tumor infiltrating B cells influences CD4 T cell phenotype and function in primary lung cancer patient tumors
creator: Bruno, Tullia
creator: Ebner, Peggy
creator: Moore, Brandon
creator: Munson, Daniel
creator: Mitchell, John
creator: Kern, Jeffrey
creator: Vignali, Dario AA
creator: Slansky, Jill
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29023/1/art%253A10.1186%252F2051-1426-3-S2-P397.pdf
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rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29023/7/licence.txt
identifier:   Bruno, Tullia and Ebner, Peggy and Moore, Brandon and Munson, Daniel and Mitchell, John and Kern, Jeffrey and Vignali, Dario AA and Slansky, Jill  (2015) Antigen presentation by tumor infiltrating B cells influences CD4 T cell phenotype and function in primary lung cancer patient tumors.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p397
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29014/
title: CD8+ T cell responses in metastatic melanoma patients receiving an adenovirally antigen engineered dendritic cell vaccine +/- IFN-α
creator: Du, Samuel
creator: Santos, Patricia M
creator: Tawbi, Hussein
creator: Tarhini, Ahmad
creator: Kirkwood, John M
creator: Butterfield, Lisa H
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29014/1/art%253A10.1186%252F2051-1426-3-S2-P149.pdf
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rights: attached
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identifier:   Du, Samuel and Santos, Patricia M and Tawbi, Hussein and Tarhini, Ahmad and Kirkwood, John M and Butterfield, Lisa H  (2015) CD8+ T cell responses in metastatic melanoma patients receiving an adenovirally antigen engineered dendritic cell vaccine +/- IFN-α.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p149
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29189/
title: Collaborative implementation of screening, brief intervention, and referral to treatment within the medical community of Blair County, PA
creator: Pringle, Janice
creator: Rickard-Aasen, Sherry
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29189/1/art%253A10.1186%252F1940-0640-10-S2-O43.pdf
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identifier: http://d-scholarship-dev.library.pitt.edu/29189/7/licence.txt
identifier:   Pringle, Janice and Rickard-Aasen, Sherry  (2015) Collaborative implementation of screening, brief intervention, and referral to treatment within the medical community of Blair County, PA.  Addiction Science &amp; Clinical Practice, 10 (S2).       
relation: 10.1186/1940-0640-10-s2-o43
language: en

relation: http://d-scholarship-dev.library.pitt.edu/39780/
title: Consumer preferences between hypermarkets and traditional retail shophouses: A case study of Kulim consumers
creator: Wong, Wei Mei
publisher: Asian Research Service
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/39780/1/Wong_2015_Consumer%20Preference.pdf
identifier:   Wong, Wei Mei  (2015) Consumer preferences between hypermarkets and traditional retail shophouses: A case study of Kulim consumers.  Asian Profile, 43 (6).  pp. 559-577.  ISSN 0304-8675     

relation: http://d-scholarship-dev.library.pitt.edu/29414/
title: Decreased coronary artery distensibility measured using 3T MRI is related to systemic inflammation in patients with coronary artery disease
creator: Petrose, Lia
creator: iantorno, micaela
creator: Soleimanifard, Sahar
creator: Kelle, Sebastian
creator: Gerstenblith, Gary
creator: Weiss, Robert
creator: Hays, Allison
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29414/1/art%253A10.1186%252F1532-429X-17-S1-P400.pdf
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identifier:   Petrose, Lia and iantorno, micaela and Soleimanifard, Sahar and Kelle, Sebastian and Gerstenblith, Gary and Weiss, Robert and Hays, Allison  (2015) Decreased coronary artery distensibility measured using 3T MRI is related to systemic inflammation in patients with coronary artery disease.  Journal of Cardiovascular Magnetic Resonance, 17 (S1).       
relation: 10.1186/1532-429x-17-s1-p400
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29198/
title: Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults
creator: Mersha, Mahlet D.
creator: Patel, Bansri M.
creator: Patel, Dipen
creator: Richardson, Brittany N.
creator: Dhillon, Harbinder S.
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29198/1/art%253A10.1186%252Fs12993-015-0071-y.pdf
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identifier: http://d-scholarship-dev.library.pitt.edu/29198/7/licence.txt
identifier:   Mersha, Mahlet D. and Patel, Bansri M. and Patel, Dipen and Richardson, Brittany N. and Dhillon, Harbinder S.  (2015) Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults.  Behavioral and Brain Functions, 11 (1).       
relation: 10.1186/s12993-015-0071-y

relation: http://d-scholarship-dev.library.pitt.edu/29008/
title: Efficacy of adoptive transfer of expanded fetal liver-derived precursor syngeneic and allogeneic murine NK cells against solid tumors
creator: Liang, Xiaoyan
creator: Wang, Wenqian
creator: Li, Guanqiao
creator: Zhang, Xiaokui
creator: Jankovic, Vladimir
creator: Herzberg, Uri
creator: Hofgartner, Wolfgang
creator: Lotze, Michael T
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29008/1/art%253A10.1186%252F2051-1426-3-S2-P30.pdf
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language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29008/7/licence.txt
identifier:   Liang, Xiaoyan and Wang, Wenqian and Li, Guanqiao and Zhang, Xiaokui and Jankovic, Vladimir and Herzberg, Uri and Hofgartner, Wolfgang and Lotze, Michael T  (2015) Efficacy of adoptive transfer of expanded fetal liver-derived precursor syngeneic and allogeneic murine NK cells against solid tumors.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p30
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29028/
title: Elucidating the role of Neuropilin-1 in intra-tumoral regulatory T cell stability
creator: Overacre, Abigail E
creator: Chikina, Maria
creator: Delgoffe, Greg M
creator: Vignali, Dario AA
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29028/1/art%253A10.1186%252F2051-1426-3-S2-P274.pdf
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language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29028/7/licence.txt
identifier:   Overacre, Abigail E and Chikina, Maria and Delgoffe, Greg M and Vignali, Dario AA  (2015) Elucidating the role of Neuropilin-1 in intra-tumoral regulatory T cell stability.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p274
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29056/
title: Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program
creator: Alfaro, Karla M.
creator: Gage, Julia C.
creator: Rosenbaum, Alan J.
creator: Ditzian, Lauren R.
creator: Maza, Mauricio
creator: Scarinci, Isabel C.
creator: Miranda, Esmeralda
creator: Villalta, Sofia
creator: Felix, Juan C.
creator: Castle, Philip E.
creator: Cremer, Miriam L.
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29056/1/art%253A10.1186%252Fs12889-015-2360-7.pdf
format: text/plain
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rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29056/7/licence.txt
identifier:   Alfaro, Karla M. and Gage, Julia C. and Rosenbaum, Alan J. and Ditzian, Lauren R. and Maza, Mauricio and Scarinci, Isabel C. and Miranda, Esmeralda and Villalta, Sofia and Felix, Juan C. and Castle, Philip E. and Cremer, Miriam L.  (2015) Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program.  BMC Public Health, 15 (1).       
relation: 10.1186/s12889-015-2360-7

relation: http://d-scholarship-dev.library.pitt.edu/28936/
title: The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients
creator: Lenna, Stefania
creator: Assassi, Shervin
creator: Farina, G Alessandra
creator: Mantero, Julio C
creator: Scorza, Raffaella
creator: Lafyatis, Robert
creator: Farber, Harrison W
creator: Trojanowska, Maria
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28936/1/art%253A10.1186%252Fs13075-015-0881-1.pdf
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rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28936/7/licence.txt
identifier:   Lenna, Stefania and Assassi, Shervin and Farina, G Alessandra and Mantero, Julio C and Scorza, Raffaella and Lafyatis, Robert and Farber, Harrison W and Trojanowska, Maria  (2015) The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.  Arthritis Research &amp; Therapy, 17 (1).       
relation: 10.1186/s13075-015-0881-1
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29022/
title: IDH mutation-induced suppression of type-1 anti-glioma immune response
creator: Kohanbash, Gary
creator: Shrivastav, Shruti
creator: Ahn, Brian
creator: Hou, Yafei
creator: Costello, Joseph
creator: Okada, Hideho
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29022/1/art%253A10.1186%252F2051-1426-3-S2-P271.pdf
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identifier: http://d-scholarship-dev.library.pitt.edu/29022/7/licence.txt
identifier:   Kohanbash, Gary and Shrivastav, Shruti and Ahn, Brian and Hou, Yafei and Costello, Joseph and Okada, Hideho  (2015) IDH mutation-induced suppression of type-1 anti-glioma immune response.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p271
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29207/
title: Identification and characterization of novel NF-kB dependent genes involved in HTLV-I pathogenesis
creator: Qu, Zhaoxia
creator: Xiao, Gutian
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29207/1/art%253A10.1186%252F1742-4690-12-S1-P93.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29207/7/licence.txt
identifier:   Qu, Zhaoxia and Xiao, Gutian  (2015) Identification and characterization of novel NF-kB dependent genes involved in HTLV-I pathogenesis.  Retrovirology, 12 (S1).       
relation: 10.1186/1742-4690-12-s1-p93
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29033/
title: Immunotherapeutic targeting of HSP90 client proteins in BRAF-inhibitor resistant melanoma
creator: Fecek, Ronald J
creator: Wang, Simeng
creator: Storkus, Walter J
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29033/1/art%253A10.1186%252F2051-1426-3-S2-P432.pdf
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language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29033/7/licence.txt
identifier:   Fecek, Ronald J and Wang, Simeng and Storkus, Walter J  (2015) Immunotherapeutic targeting of HSP90 client proteins in BRAF-inhibitor resistant melanoma.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p432
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29001/
title: Impact of annual hospital volume of high dose interleukin-2 infusions on in-patient mortality in patients with melanoma and renal cell carcinoma
creator: Mehta, Kathan
creator: Appleman, Leonard
creator: Wang, Hong
creator: Tarhini, Ahmad
creator: Parikh, Rahul
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29001/1/art%253A10.1186%252F2051-1426-3-S2-P234.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29001/7/licence.txt
identifier:   Mehta, Kathan and Appleman, Leonard and Wang, Hong and Tarhini, Ahmad and Parikh, Rahul  (2015) Impact of annual hospital volume of high dose interleukin-2 infusions on in-patient mortality in patients with melanoma and renal cell carcinoma.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p234
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29192/
title: Implementing Screening and Brief Intervention in Community Pharmacies to Improve Medication Adherence
creator: Pringle, Janice
creator: Boyer, Annette D
creator: Conklin, Mark H
creator: Aldridge, Arnie
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29192/1/art%253A10.1186%252F1940-0640-10-S2-P14.pdf
format: text/plain
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rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29192/7/licence.txt
identifier:   Pringle, Janice and Boyer, Annette D and Conklin, Mark H and Aldridge, Arnie  (2015) Implementing Screening and Brief Intervention in Community Pharmacies to Improve Medication Adherence.  Addiction Science &amp; Clinical Practice, 10 (S2).       
relation: 10.1186/1940-0640-10-s2-p14
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29000/
title: Level of PD-1 expression on CD8+ T cells influence prognosis and respond to PD-1 therapy in a murine model
creator: Kansy, Benjamin A
creator: Srivastava, Raghvendra M
creator: Jie, Hyun-Bae
creator: Shayan, Gulidanna
creator: Lei, Yu
creator: Li, Jing
creator: Gooding, William
creator: Brandau, Sven
creator: Lang, Stephan
creator: Schmitt, Nicole
creator: Freeman, Gordon J
creator: Clump, David A
creator: Ferris, Robert L
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29000/1/art%253A10.1186%252F2051-1426-3-S2-P228.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29000/7/licence.txt
identifier:   Kansy, Benjamin A and Srivastava, Raghvendra M and Jie, Hyun-Bae and Shayan, Gulidanna and Lei, Yu and Li, Jing and Gooding, William and Brandau, Sven and Lang, Stephan and Schmitt, Nicole and Freeman, Gordon J and Clump, David A and Ferris, Robert L  (2015) Level of PD-1 expression on CD8+ T cells influence prognosis and respond to PD-1 therapy in a murine model.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p228
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29050/
title: Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
creator: Sznol, Mario
creator: Fishman, Mayer
creator: Escudier, Bernard
creator: McDermott, David F
creator: Kluger, Harriet
creator: Stadler, Walter M
creator: Perez-Gracia, Jose
creator: McNeel, Douglas G
creator: Curti, Brendan D
creator: Harrison, Michael R
creator: Plimack, Elizabeth R
creator: Appleman, Leonard
creator: Fong, Lawrence
creator: Drake, Charles G
creator: Young, Tina C
creator: Chasalow, Scott D
creator: Ross-MacDonald, Petra
creator: Simon, Jason S
creator: Walker, Dana
creator: Choueiri, Toni K
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29050/1/art%253A10.1186%252F2051-1426-3-S2-P197.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29050/7/licence.txt
identifier:   Sznol, Mario and Fishman, Mayer and Escudier, Bernard and McDermott, David F and Kluger, Harriet and Stadler, Walter M and Perez-Gracia, Jose and McNeel, Douglas G and Curti, Brendan D and Harrison, Michael R and Plimack, Elizabeth R and Appleman, Leonard and Fong, Lawrence and Drake, Charles G and Young, Tina C and Chasalow, Scott D and Ross-MacDonald, Petra and Simon, Jason S and Walker, Dana and Choueiri, Toni K  (2015) Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p197
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29186/
title: Organizational characteristics, outcomes and resource use in ICUs: the ORCHESTRA Study
creator: Angus, Derek C
creator: Bozza, Fernando
creator: Kahn, Jeremy
creator: Salluh, Jorge
creator: Soares, Marcio
creator: Investigators, ORCHESTRA Study
creator: Brasil, Pedro
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29186/1/art%253A10.1186%252Fcc14684.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29186/7/licence.txt
identifier:   Angus, Derek C and Bozza, Fernando and Kahn, Jeremy and Salluh, Jorge and Soares, Marcio and Investigators, ORCHESTRA Study and Brasil, Pedro  (2015) Organizational characteristics, outcomes and resource use in ICUs: the ORCHESTRA Study.  Critical Care, 19 (S2).       
relation: 10.1186/cc14684
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29012/
title: PD-1 is a marker of activation on tumor infiltrating NK cells in head and neck cancer
creator: Concha-Benavente, Fernando
creator: Srivastava, Raghvendra M
creator: Kansy, Benjamin
creator: Ferris, Robert L
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29012/1/art%253A10.1186%252F2051-1426-3-S2-P398.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29012/7/licence.txt
identifier:   Concha-Benavente, Fernando and Srivastava, Raghvendra M and Kansy, Benjamin and Ferris, Robert L  (2015) PD-1 is a marker of activation on tumor infiltrating NK cells in head and neck cancer.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p398
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29048/
title: A Phase I/III, multicenter, open-label trial of talimogene laherparepvec (T-VEC) in combination with pembrolizumab for the treatment of unresected, stage IIIb-IV melanoma (MASTERKEY-265)
creator: Long, Georgina V
creator: Dummer, Reinhard
creator: Ribas, Antoni
creator: Puzanov, Igor
creator: Michielin, Olivier
creator: VanderWalde, Ari
creator: Andtbacka, Robert HI
creator: Cebon, Jonathan
creator: Fernandez, Eugenio
creator: Malvehy, Josep
creator: Olszanski, Anthony J
creator: Gajewski, Thomas F
creator: Kirkwood, John M
creator: Kuznetsova, Olga
creator: Chen, Lisa
creator: Kaufman, David R
creator: Chou, Jeffrey
creator: Hodi, F Stephen
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29048/1/art%253A10.1186%252F2051-1426-3-S2-P181.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29048/7/licence.txt
identifier:   Long, Georgina V and Dummer, Reinhard and Ribas, Antoni and Puzanov, Igor and Michielin, Olivier and VanderWalde, Ari and Andtbacka, Robert HI and Cebon, Jonathan and Fernandez, Eugenio and Malvehy, Josep and Olszanski, Anthony J and Gajewski, Thomas F and Kirkwood, John M and Kuznetsova, Olga and Chen, Lisa and Kaufman, David R and Chou, Jeffrey and Hodi, F Stephen  (2015) A Phase I/III, multicenter, open-label trial of talimogene laherparepvec (T-VEC) in combination with pembrolizumab for the treatment of unresected, stage IIIb-IV melanoma (MASTERKEY-265).  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p181
language: en

relation: http://d-scholarship-dev.library.pitt.edu/28937/
title: Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial
creator: Yardley, Denise A
creator: Brufsky, Adam
creator: Coleman, Robert E
creator: Conte, Pierfranco F
creator: Cortes, Javier
creator: Glück, Stefan
creator: Nabholtz, Jean-Mark A
creator: O’Shaughnessy, Joyce
creator: Beck, Robert M
creator: Ko, Amy
creator: Renschler, Markus F
creator: Barton, Debora
creator: Harbeck, Nadia
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28937/1/art%253A10.1186%252Fs13063-015-1101-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28937/7/licence.txt
identifier:   Yardley, Denise A and Brufsky, Adam and Coleman, Robert E and Conte, Pierfranco F and Cortes, Javier and Glück, Stefan and Nabholtz, Jean-Mark A and O’Shaughnessy, Joyce and Beck, Robert M and Ko, Amy and Renschler, Markus F and Barton, Debora and Harbeck, Nadia  (2015) Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial.  Trials, 16 (1).       
relation: 10.1186/s13063-015-1101-7
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29049/
title: Phase III, randomized, open-label study of durvalumab (MEDI4736) monotherapy, or durvalumab + tremelimumab, versus standard of care (SoC), in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): eagle
creator: Ferris, Robert L
creator: Even, Caroline
creator: Haddad, Robert
creator: Tahara, Makoto
creator: Goswami, Trishna
creator: Franks, April
creator: Emeribe, Ugochi
creator: Jarkowski, Anthony
creator: Melillo, Giovanni
creator: Licitra, Lisa
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29049/1/art%253A10.1186%252F2051-1426-3-S2-P150.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29049/7/licence.txt
identifier:   Ferris, Robert L and Even, Caroline and Haddad, Robert and Tahara, Makoto and Goswami, Trishna and Franks, April and Emeribe, Ugochi and Jarkowski, Anthony and Melillo, Giovanni and Licitra, Lisa  (2015) Phase III, randomized, open-label study of durvalumab (MEDI4736) monotherapy, or durvalumab + tremelimumab, versus standard of care (SoC), in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): eagle.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p150
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29236/
title: Physician burnout: can we make a difference together?
creator: Siedsma, Matthew
creator: Emlet, Lillian
description: <jats:title>Expanded abstract</jats:title><jats:sec> <jats:title>Citation</jats:title> <jats:p>West CP, Dyrbye LN, Rabatin JT, Call TG, Davidson JH, Multari A, Romanski SA, Hellyer JMH, Sloan JA, Shanafelt TF. Intervention to promote physician well-being, job satisfaction, and professionalism: a randomized clinical trial. JAMA Intern Med. 2014;174:527–33.</jats:p> </jats:sec><jats:sec> <jats:title>Background</jats:title> <jats:p>Despite the documented prevalence and clinical ramifications of physician distress, few rigorous studies have tested interventions to address the problem.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p><jats:italic>Objective:</jats:italic> To test the hypothesis that an intervention involving a facilitated physician small-group curriculum would result in improvement in well-being.</jats:p> <jats:p><jats:italic>Design:</jats:italic> A randomized clinical trial of practicing physicians. Additional data were collected on nontrial participants responding to annual surveys timed to coincide with the trial surveys.</jats:p> <jats:p><jats:italic>Setting:</jats:italic> Department of Medicine at the Mayo Clinic in Rochester, Minnesota between September 2010 and June 2012.</jats:p> <jats:p><jats:italic>Participants:</jats:italic> The study involved 74 practicing physicians in the Department of Medicine and 350 nontrial participants responding to annual surveys.</jats:p> <jats:p><jats:italic>Interventions:</jats:italic> The intervention involved 19 biweekly facilitated physician discussion groups incorporating elements of mindfulness, reflection, shared experience, and small-group learning for 9 months. Protected time (1 hour of paid time every other week) for participants was provided by the institution.</jats:p> <jats:p><jats:italic>Outcomes:</jats:italic> Meaning in work, empowerment and engagement in work, burnout, symptoms of depression, quality of life, and job satisfaction were assessed using validated metrics.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Empowerment and engagement at work increased by 5.3 points in the intervention arm vs. a 0.5-point decline in the control arm by 3 months after the study (<jats:italic>P</jats:italic> = .04), an improvement sustained at 12 months (+5.5 vs. +1.3 points; <jats:italic>P</jats:italic> = .03). Rates of high depersonalization at 3 months had decreased by 15.5 % in the intervention arm vs. a 0.8 % increase in the control arm (<jats:italic>P</jats:italic> = .004). This difference was also sustained at 12 months (9.6 % vs. 1.5 % decrease; <jats:italic>P</jats:italic> = .02). No statistically significant differences in stress, symptoms of depression, overall quality of life, or job satisfaction were seen. In additional comparisons including the nontrial physician cohort, the proportion of participants strongly agreeing that their work was meaningful increased 6.3 % in the study intervention arm but decreased 6.3 % in the study control arm and 13.4 % in the nonstudy cohort (<jats:italic>P</jats:italic> = .04). Rates of depersonalization, emotional exhaustion, and overall burnout decreased substantially in the trial intervention arm, decreased slightly in the trial control arm, and increased in the nontrial cohort (<jats:italic>P</jats:italic> = .03, <jats:italic>P</jats:italic> = .007, and <jats:italic>P</jats:italic> = .002 for each outcome, respectively).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>An intervention for physicians based on a facilitated small-group curriculum improved meaning and engagement in work and reduced depersonalization, with sustained results 12 months after the study.</jats:p> </jats:sec>
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29236/1/art%253A10.1186%252Fs13054-015-0990-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29236/7/licence.txt
identifier:   Siedsma, Matthew and Emlet, Lillian  (2015) Physician burnout: can we make a difference together?  Critical Care, 19 (1).       
relation: 10.1186/s13054-015-0990-x
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29211/
title: Pilot trial of a type I - polarized autologous dendritic cell vaccine incorporating tumor blood vessel antigen-derived peptides in patients with metastatic breast cancer
creator: Baar, Joseph
creator: Storkus, Walter J
creator: Finke, James
creator: Butterfield, Lisa
creator: Lazarus, Hillard
creator: Reese, Jane
creator: Downes, Katharine
creator: Budd, Thomas
creator: Brufsky, Adam
creator: Fu, Pingfu
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29211/1/art%253A10.1186%252F2051-1426-3-S1-P3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29211/7/licence.txt
identifier:   Baar, Joseph and Storkus, Walter J and Finke, James and Butterfield, Lisa and Lazarus, Hillard and Reese, Jane and Downes, Katharine and Budd, Thomas and Brufsky, Adam and Fu, Pingfu  (2015) Pilot trial of a type I - polarized autologous dendritic cell vaccine incorporating tumor blood vessel antigen-derived peptides in patients with metastatic breast cancer.  Journal for ImmunoTherapy of Cancer, 3 (S1).       
relation: 10.1186/2051-1426-3-s1-p3
language: en

relation: http://d-scholarship-dev.library.pitt.edu/32617/
title: Reliable Communications over Multihop Networks under Routing Attacks
creator: Abdelhakim, Mai
creator: Lightfoot, Leonard
creator: Ren, Jian
creator: Li, Tongtong
publisher: IEEE
date: 2015-12
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32617/1/licence.txt
identifier:   Abdelhakim, Mai and Lightfoot, Leonard and Ren, Jian and Li, Tongtong  (2015) Reliable Communications over Multihop Networks under Routing Attacks.  2015 IEEE Global Communications Conference (GLOBECOM).       
relation: 10.1109/glocom.2015.7417404

relation: http://d-scholarship-dev.library.pitt.edu/29021/
title: Selective costimulation by IL-15R/IL-15, but not IL-2R/IL-2, allows the induction of high numbers of tumor-specific CD8+ T cells by human dendritic cells matured in conditions of acute inflammation
creator: Hansen, Morten
creator: Wieckowski, Eva
creator: Svane, Inge Marie
creator: Edwards, Robert P
creator: Kalinski, Pawel
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29021/1/art%253A10.1186%252F2051-1426-3-S2-P223.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29021/7/licence.txt
identifier:   Hansen, Morten and Wieckowski, Eva and Svane, Inge Marie and Edwards, Robert P and Kalinski, Pawel  (2015) Selective costimulation by IL-15R/IL-15, but not IL-2R/IL-2, allows the induction of high numbers of tumor-specific CD8+ T cells by human dendritic cells matured in conditions of acute inflammation.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p223
language: en

relation: http://d-scholarship-dev.library.pitt.edu/26987/
title: Titian’s Miracles: Artistry and Efficacy Between the San Rocco Christ and the Accademia Pietà
creator: Nygren, Christopher J
description: In the 1568 edition of his Lives, Giorgio Vasari attributed a miracle-working icon to Titian. The San Rocco Christ Carrying the Cross had been working miracles since 1519, and following Vasari’s attribution it was inextricably linked to Titian’s artistry. The magnitude of this claim has not been appreciated. Titian’s final painting, the Pietà (Venice, Galleria dell’Accademia), cannot be understood outside of this heritage of miraculous efficacy. This painting had been ideated as the altarpiece for Titian’s tomb. Therefore, scholars have long seen the painting as a reflection of Titian’s artistic identity. This article suggests that the painting attests to the complexity and instability of that identity as it relates to the larger question of how images and image-makers mediated the dispersal of divine grace, which had been evoked by Vasari. In his final picture Titian capitalized on the anxieties that attended his reputation as the producer of a miraculous image. While recalling this earlier moment in Titian’s career, this last painting layers references to miraculous agency by including votive objects associated with miracles; appropriating the history of the painting’s intended site; and citing a little known miracle-working image, the Madonna della Navicella. All of these coordinates point to Titian’s Pietà as the vector of miraculous grace, which is a radical claim for the artist to put forward in the wake of the Reformation and the decrees of the Council of Trent.
publisher: Max-Planck-Institut
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26987/1/Nygren_Titian%27s_Miracles_Published.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26987/4/licence.txt
identifier:   Nygren, Christopher J  (2015) Titian’s Miracles: Artistry and Efficacy Between the San Rocco Christ and the Accademia Pietà.  Mitteilungen des Kunsthistorischen Institutes in Florenz, LVII (3).  321 - 349.  ISSN 0342-1201     

relation: http://d-scholarship-dev.library.pitt.edu/29016/
title: Tumor-derived alpha fetoprotein directly impacts human natural killer cell activity and viability
creator: Vujanovic, Lazar
creator: Stahl, Elizabeth
creator: Pardee, Angela
creator: Watkins, Simon
creator: Gibson, Gregory
creator: Butterfield, Lisa H
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29016/1/art%253A10.1186%252F2051-1426-3-S2-P289.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29016/7/licence.txt
identifier:   Vujanovic, Lazar and Stahl, Elizabeth and Pardee, Angela and Watkins, Simon and Gibson, Gregory and Butterfield, Lisa H  (2015) Tumor-derived alpha fetoprotein directly impacts human natural killer cell activity and viability.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p289
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29035/
title: Tumor-derived alpha-fetoprotein (tAFP) causes immune and metabolic dysfunction in monocyte-derived dendritic cells
creator: Santos, Patricia M
creator: Pardee, Angela
creator: Delgoffe, Greg M
creator: Butterfield, Lisa H
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29035/1/art%253A10.1186%252F2051-1426-3-S2-P210.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29035/7/licence.txt
identifier:   Santos, Patricia M and Pardee, Angela and Delgoffe, Greg M and Butterfield, Lisa H  (2015) Tumor-derived alpha-fetoprotein (tAFP) causes immune and metabolic dysfunction in monocyte-derived dendritic cells.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p210
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29027/
title: The extent of metalloproteinase-mediated LAG3 cleavage limits the efficacy of PD1 blockade
creator: Andrews, Lawrence P
creator: Szymczak-Workman, Andrea L
creator: Workman, Creg J
creator: Vignali, Dario AA
publisher: BMJ
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29027/1/art%253A10.1186%252F2051-1426-3-S2-P216.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29027/7/licence.txt
identifier:   Andrews, Lawrence P and Szymczak-Workman, Andrea L and Workman, Creg J and Vignali, Dario AA  (2015) The extent of metalloproteinase-mediated LAG3 cleavage limits the efficacy of PD1 blockade.  Journal for ImmunoTherapy of Cancer, 3 (S2).       
relation: 10.1186/2051-1426-3-s2-p216
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29190/
title: A new methodology for examining the efficacy of SBIRT protocols on reducing healthcare utilization and costs
creator: Pringle, Janice
creator: Aldridge, Arnie
creator: Kearney, Shannon
publisher: Springer Science and Business Media LLC
date: 2015-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29190/1/art%253A10.1186%252F1940-0640-10-S2-O44.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29190/7/licence.txt
identifier:   Pringle, Janice and Aldridge, Arnie and Kearney, Shannon  (2015) A new methodology for examining the efficacy of SBIRT protocols on reducing healthcare utilization and costs.  Addiction Science &amp; Clinical Practice, 10 (S2).       
relation: 10.1186/1940-0640-10-s2-o44
language: en

relation: http://d-scholarship-dev.library.pitt.edu/28949/
title: Future perspectives in melanoma research: Meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014
creator: Ascierto, PA
creator: Atkins, M
creator: Bifulco, C
creator: Botti, G
creator: Cochran, A
creator: Davies, M
creator: Demaria, S
creator: Dummer, R
creator: Ferrone, S
creator: Formenti, S
creator: Gajewski, TF
creator: Garbe, C
creator: Khleif, S
creator: Kiessling, R
creator: Lo, R
creator: Lorigan, P
creator: Arthur, GM
creator: Masucci, G
creator: Melero, I
creator: Mihm, M
creator: Palmieri, G
creator: Parmiani, G
creator: Puzanov, I
creator: Romero, P
creator: Schilling, B
creator: Seliger, B
creator: Stroncek, D
creator: Taube, J
creator: Tomei, S
creator: Zarour, HM
creator: Testori, A
creator: Wang, E
creator: Galon, J
creator: Ciliberto, G
creator: Mozzillo, N
creator: Marincola, FM
creator: Thurin, M
description: The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.
date: 2015-11-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28949/1/art%253A10.1186%252Fs12967-015-0736-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28949/7/licence.txt
identifier:   Ascierto, PA and Atkins, M and Bifulco, C and Botti, G and Cochran, A and Davies, M and Demaria, S and Dummer, R and Ferrone, S and Formenti, S and Gajewski, TF and Garbe, C and Khleif, S and Kiessling, R and Lo, R and Lorigan, P and Arthur, GM and Masucci, G and Melero, I and Mihm, M and Palmieri, G and Parmiani, G and Puzanov, I and Romero, P and Schilling, B and Seliger, B and Stroncek, D and Taube, J and Tomei, S and Zarour, HM and Testori, A and Wang, E and Galon, J and Ciliberto, G and Mozzillo, N and Marincola, FM and Thurin, M  (2015) Future perspectives in melanoma research: Meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.  Journal of Translational Medicine, 13 (1).       
relation: 10.1186/s12967-015-0736-1

relation: http://d-scholarship-dev.library.pitt.edu/28950/
title: A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity
creator: Dixon, AE
creator: Subramanian, M
creator: DeSarno, M
creator: Black, K
creator: Lane, L
creator: Holguin, F
description: Background: Obese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications. The purpose of this study was to determine the efficacy of pioglitazone, an anti-diabetic medication which can alter circulating adipokines and have direct effects on asthmatic inflammation, in the treatment of asthma in obesity. Methods: A two-center, 12-week, randomized, placebo-controlled, double-blinded trial. Treatments were randomly assigned with concealment of allocation. The primary outcome was difference in change in airway reactivity between participants assigned to pioglitazone versus placebo at 12weeks. Results: Twenty-three participants were randomized to treatment, 19 completed the study. Median airway reactivity, measured by PC20 to methacholine was 1.99 (IQR 3.08) and 1.60 (5.91) mg/ml in placebo and pioglitazone group at baseline, and 2.37 (15.22) and 5.08 (7.42) mg/ml after 12weeks, p=0.38. There was no difference in exhaled nitric oxide, asthma control or lung function between treatment groups over the 12week trial. Participants assigned to pioglitazone gained a significant amount more weight than those assigned to placebo (pioglitazone group mean weight 113.6, CI 94.5-132.7kg at randomization and 115.9, CI 96.9-135.1 at 12weeks; placebo mean weight 127.5, CI 108.4 - 146.6kg at randomization and 124.5, CI 105.4 - 143.6kg at 12weeks; p=0.04). Conclusions: This pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma. Trial Registration: Clinicaltrials.gov (NCT00634036)
date: 2015-11-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28950/1/art%253A10.1186%252Fs12931-015-0303-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28950/7/licence.txt
identifier:   Dixon, AE and Subramanian, M and DeSarno, M and Black, K and Lane, L and Holguin, F  (2015) A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity.  Respiratory Research, 16 (1).   ISSN 1465-9921     
relation: 10.1186/s12931-015-0303-6

relation: http://d-scholarship-dev.library.pitt.edu/28952/
title: Lipid levels in HIV-positive men receiving anti-retroviral therapy are not associated with copy number variation of reverse cholesterol transport pathway genes Genetics
creator: Marino, RB
creator: Kingsley, LA
creator: Hussain, SK
creator: Bream, JH
creator: Penogonda, S
creator: Duggal, P
creator: Martinson, JJ
description: Background: The exacerbation of HIV-1 associated dyslipidemia seen in a subset of patients receiving anti-retroviral therapy suggests that genetic factors put these individuals at greater risk of cardiovascular disease. Single nucleotide polymorphisms (SNPs) within genes of and influencing the reverse cholesterol transport (RCT) pathway are associated with lipid levels but little is known regarding their copy number variation (CNV). This form of quantitative genetic variation has the potential to alter the amount of gene product made, thereby also influencing lipid metabolism. Results: To examine if CNV in RCT pathway genes was associated with altered serum lipid profiles in HIV-positive individuals receiving therapy, we designed a custom multiplex ligation-dependent probe amplification assay to screen 16 RCT genes within a subset of individuals from the Multicenter AIDS Cohort Study who show extreme lipid phenotypes. Verification of CNV was performed using a custom NanoString assay, and the Illumina HT-12 mRNA expression microarray was used to determine the influence of copy number on gene expression. Among the RCT genes, CNV was observed to be extremely rare. The only CNV seen was in the CETP gene, which showed a loss of copy in 1 of the 320 samples (0.3 %) in our study. The genes in our study showed little variation in expression between individuals, and the variation seen was not related to any detected CNV. Conclusions: Whole gene CNV is uncommon in RCT pathway genes, and not a major factor in the development of highly active antiretroviral therapy (HAART) associated dyslipidemia.
date: 2015-11-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28952/1/art%253A10.1186%252Fs13104-015-1665-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28952/7/licence.txt
identifier:   Marino, RB and Kingsley, LA and Hussain, SK and Bream, JH and Penogonda, S and Duggal, P and Martinson, JJ  (2015) Lipid levels in HIV-positive men receiving anti-retroviral therapy are not associated with copy number variation of reverse cholesterol transport pathway genes Genetics.  BMC Research Notes, 8 (1).       
relation: 10.1186/s13104-015-1665-z

relation: http://d-scholarship-dev.library.pitt.edu/28953/
title: A functional genomic model for predicting prognosis in idiopathic pulmonary fibrosis
creator: Huang, Y
creator: Ma, SF
creator: Vij, R
creator: Oldham, JM
creator: Herazo-Maya, J
creator: Broderick, SM
creator: Strek, ME
creator: White, SR
creator: Hogarth, DK
creator: Sandbo, NK
creator: Lussier, YA
creator: Gibson, KF
creator: Kaminski, N
creator: Garcia, JGN
creator: Noth, I
description: Background: The course of disease for patients with idiopathic pulmonary fibrosis (IPF) is highly heterogeneous. Prognostic models rely on demographic and clinical characteristics and are not reproducible. Integrating data from genomic analyses may identify novel prognostic models and provide mechanistic insights into IPF. Methods: Total RNA of peripheral blood mononuclear cells was subjected to microarray profiling in a training (45 IPF individuals) and two independent validation cohorts (21 IPF/10 controls, and 75 IPF individuals, respectively). To identify a gene set predictive of IPF prognosis, we incorporated genomic, clinical, and outcome data from the training cohort. Predictor genes were selected if all the following criteria were met: 1) Present in a gene co-expression module from Weighted Gene Co-expression Network Analysis (WGCNA) that correlated with pulmonary function (p < 0.05); 2) Differentially expressed between observed "good" vs. "poor" prognosis with fold change (FC) >1.5 and false discovery rate (FDR) < 2 %; and 3) Predictive of mortality (p < 0.05) in univariate Cox regression analysis. "Survival risk group prediction" was adopted to construct a functional genomic model that used the IPF prognostic predictor gene set to derive a prognostic index (PI) for each patient into either high or low risk for survival outcomes. Prediction accuracy was assessed with a repeated 10-fold cross-validation algorithm and independently assessed in two validation cohorts through multivariate Cox regression survival analysis. Results: A set of 118 IPF prognostic predictor genes was used to derive the functional genomic model and PI. In the training cohort, high-risk IPF patients predicted by PI had significantly shorter survival compared to those labeled as low-risk patients (log rank p < 0.001). The prediction accuracy was further validated in two independent cohorts (log rank p < 0.001 and 0.002). Functional pathway analysis revealed that the canonical pathways enriched with the IPF prognostic predictor gene set were involved in T-cell biology, including iCOS, T-cell receptor, and CD28 signaling. Conclusions: Using supervised and unsupervised analyses, we identified a set of IPF prognostic predictor genes and derived a functional genomic model that predicted high and low-risk IPF patients with high accuracy. This genomic model may complement current prognostic tools to deliver more personalized care for IPF patients.
date: 2015-11-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28953/1/art%253A10.1186%252Fs12890-015-0142-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28953/7/licence.txt
identifier:   Huang, Y and Ma, SF and Vij, R and Oldham, JM and Herazo-Maya, J and Broderick, SM and Strek, ME and White, SR and Hogarth, DK and Sandbo, NK and Lussier, YA and Gibson, KF and Kaminski, N and Garcia, JGN and Noth, I  (2015) A functional genomic model for predicting prognosis in idiopathic pulmonary fibrosis.  BMC Pulmonary Medicine, 15 (1).       
relation: 10.1186/s12890-015-0142-8

relation: http://d-scholarship-dev.library.pitt.edu/29275/
title: Alcohol brief intervention for hospitalized veterans with hazardous drinking: Protocol for a 3-arm randomized controlled efficacy trial
creator: Broyles, LM
creator: Wieland, ME
creator: Confer, AL
creator: Dinardo, MM
creator: Kraemer, KL
creator: Hanusa, BH
creator: Youk, AO
creator: Gordon, AJ
creator: Sevick, MA
description: Background: Various hospital accreditation and quality assurance entities in the United States have approved and endorsed performance measures promoting alcohol brief intervention (BI) for hospitalized individuals who screen positive for unhealthy alcohol use, the spectrum of use ranging from hazardous use to alcohol use disorders. These performance measures have been controversial due to the limited and equivocal evidence for the efficacy of BI among hospitalized individuals. The few BI trials conducted with hospital inpatients vary widely in methodological quality. While the majority of these studies indicate limited to no effects of BI in this population, none have been designed to account for the most pervasive methodological issue in BI studies presumed to drive study findings towards the null: assessment reactivity (AR). Methods/Design: This is a three-arm, single-site, randomized controlled trial of BI for hospitalized patients at a large academic medical center affiliated with the U.S. Department of Veterans Affairs who use alcohol at hazardous levels but do not have an alcohol use disorder. Participants are randomized to one of three study conditions. Study Arm 1 receives a three-part alcohol BI. Study Arm 2 receives attention control. To account for potential AR, Study Arm 3 receives AC with limited assessment. Primary outcomes will include the number of standard drinks/week and binge drinking episodes reported in the 30-day period prior to a final measurement visit obtained 6 months after hospital discharge. Additional outcomes will include readiness to change drinking behavior and number of adverse consequences of alcohol use. To assess differences in primary outcomes across the three arms, we will use mixed-effects regression models that account for a patient's repeated measures over the timepoints and clustering within medical units. Intervention implementation will be assessed by: a) review of intervention audio recordings to characterize barriers to intervention fidelity; and b) feasibility of participant recruitment, enrollment, and follow-up. Discussion: The results of this methodologically rigorous trial will provide greater justification for or against the use of BI performance measures in the inpatient setting and inform organizational responses to BI-related hospital accreditation and performance measures. Trial registration: NCT01602172
date: 2015-11-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29275/1/art%253A10.1186%252Fs13722-015-0033-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29275/7/licence.txt
identifier:   Broyles, LM and Wieland, ME and Confer, AL and Dinardo, MM and Kraemer, KL and Hanusa, BH and Youk, AO and Gordon, AJ and Sevick, MA  (2015) Alcohol brief intervention for hospitalized veterans with hazardous drinking: Protocol for a 3-arm randomized controlled efficacy trial.  Addiction Science and Clinical Practice, 10 (1).   ISSN 1940-0632     
relation: 10.1186/s13722-015-0033-6

relation: http://d-scholarship-dev.library.pitt.edu/29113/
title: Where is the vascular waterfall in septic shock?
creator: Kato, Ryotaro
creator: Pinsky, Michael
description: <ns4:p>An evaluation of a recent study by Asfar P, Meziani F, Hamel J-F, <ns4:italic>et al</ns4:italic>. <ns4:bold>High versus low blood-pressure target in patients with septic shock</ns4:bold>. N Engl J Med 2014;370:1583-1593.</ns4:p>
publisher: F1000 Research Ltd
date: 2015-11-19
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29113/1/10.12688_f1000research.6820.1_20151120.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29113/7/licence.txt
identifier:   Kato, Ryotaro and Pinsky, Michael  (2015) Where is the vascular waterfall in septic shock?  F1000Research, 4.  1294 - 1294.      
relation: 10.12688/f1000research.6820.1
language: en

relation: http://d-scholarship-dev.library.pitt.edu/28954/
title: What is the right temperature to cool post-cardiac arrest patients?
creator: Chandrasekaran, PN
creator: Dezfulian, C
creator: Polderman, KH
description: Background: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34°C for 12 to 24hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome. Methods: Objective: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36°C reduces all-cause mortality compared with a moderate hypothermia of 33°C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures. Design: A multicenter, international, open label, randomized controlled trial. Setting: Thirty-six ICUs in Europe and Australia participated in this study. Participants: Unconscious adults (older than 18years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20minutes without chest compressions). Intervention: The above participant cohorts were randomized to targeted body temperature of either 33°C or 36°C for 36hours after the CA with gradual rewarming of both groups to 37°C (hourly increments of 0.5°C) after the initial 28hours. Body temperatures in both the groups were then maintained below 37.5°C for 72hours after the initial 36hours. Outcomes: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180days were studied. Results: Out of the 939 participants, all-cause mortality at the end of the trial was 50% in the 33°C group (225 of 466 patients) compared with 48% in the 36°C group (235 of 473 patients); the hazard ratio with a temperature of 33°C was 1.06 (95% confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180days, 54% of patients in the 33°C group versus 52% in the 36°C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95% CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180days was unchanged (52%) in both groups (risk ratio 1.01, 95% CI 0.89 to 1.14, P = 0.87). Conclusions: Maintaining targeted lower normothermia of 36°C had similar outcomes compared with induced moderate hypothermia of 33°C for unconscious survivors of OHCA of presumed cardiac cause.
date: 2015-11-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28954/1/art%253A10.1186%252Fs13054-015-1134-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28954/7/licence.txt
identifier:   Chandrasekaran, PN and Dezfulian, C and Polderman, KH  (2015) What is the right temperature to cool post-cardiac arrest patients?  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-1134-z

relation: http://d-scholarship-dev.library.pitt.edu/28957/
title: Cartilage stem/progenitor cells are activated in osteoarthritis via interleukin-1β/nerve growth factor signaling
creator: Jiang, Y
creator: Hu, C
creator: Yu, S
creator: Yan, J
creator: Peng, H
creator: Ouyang, HW
creator: Tuan, RS
description: Introduction: Interleukin-1β (IL-1β) and nerve growth factor (NGF) are key regulators in the pathogenesis of inflammatory arthritis; specifically, IL-1β is involved in tissue degeneration and NGF is involved in joint pain. However, the cellular and molecular interactions between IL-1β and NGF in articular cartilage are not known. Cartilage stem/progenitor cells (CSPCs) have recently been identified in osteoarthritic (OA) cartilage on the basis of their migratory properties. Here we hypothesize that IL-1β/NGF signaling is involved in OA cartilage degeneration by targeting CSPCs. Method: NGF and NGF receptor (NGFR: TrkA and p75NTR) expression in healthy and OA human articular cartilage and isolated chondrocytes was determined by immunostaining, qRT-PCR, flow cytometry and western blot. Articular cartilage derived stem/progenitor cells were collected and identified by stem/progenitor cell characteristics. 3D-cultured CSPC pellets and cartilage explants were treated with NGF and NGF neutralizing antibody, and extracellular matrix changes were examined by sulfated glycosaminoglycan (GAG) release and MMP expression and activity. Results: Expression of NGF, TrkA and p75NTR was found to be elevated in human OA cartilage. Cellular changes upon IL-1β and/or NGF treatment were then examined. NGF mRNA and NGFR proteins levels were upregulated in cultured chondrocytes exposed to IL-1β. NGF was chemotactic for cells isolated from OA cartilage. Cells isolated on the basis of their chemotactic migration towards NGF demonstrated stem/progenitor cell characteristics, including colony-forming ability, multi-lineage differentiation potential, and stem cell surface markers. The effects of NGF perturbation in cartilage explants and 3D-cultured CSPCs were next analyzed. NGF treatment resulted in extracellular matrix catabolism indicated by increased sGAG release and MMP expression and activity; conversely, treatment with NGF neutralizing antibody inhibited increased MMP levels, and enhanced tissue inhibitor of matrix metalloprotease-1 (TIMP1) expression in OA cartilage explants. NGF blockade with neutralizing antibody also affected cartilage matrix remodeling in 3D-CSPC pellet cultures. Conclusion: Our results strongly suggest that NGF signaling is a contributing factor in articular cartilage degeneration in OA, which likely targets a specific subpopulation of progenitor cells, the CSPCs, affecting their migratory and matrix remodeling activities. These findings provide novel cellular/signaling therapeutic targets in osteoarthritic cartilage.
date: 2015-11-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28957/1/art%253A10.1186%252Fs13075-015-0840-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28957/7/licence.txt
identifier:   Jiang, Y and Hu, C and Yu, S and Yan, J and Peng, H and Ouyang, HW and Tuan, RS  (2015) Cartilage stem/progenitor cells are activated in osteoarthritis via interleukin-1β/nerve growth factor signaling.  Arthritis Research and Therapy, 17 (1).   ISSN 1478-6354     
relation: 10.1186/s13075-015-0840-x

relation: http://d-scholarship-dev.library.pitt.edu/28956/
title: Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients
creator: Li, J
creator: Srivastava, RM
creator: Ettyreddy, A
creator: Ferris, RL
description: Background: Myeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity. Methods: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) on the UPCI 08-013 NCT01218048 trial were treated with single-agent cetuximab before surgery. Blood were collected pre- and post-cetuximab treatment to analyze frequency of monocytic MDSC (CD11b+CD14+HLA-DRlo/-), granulocytic MDSC (LIN-CD11b+CD15+) and CD11b+CD14+HLA-DRhi monocytes by flow cytometry. Besides, CD11b+CD14+HLA-DRhi monocytes were sorted for qPCR analysis of IL-10 and IL-12B transcripts. MDSC were generated in vitro with or without coated hIgG1 and tested for suppressive activity in mixed leukocyte reaction (MLR). Naïve monocytes from HNSCC patients co-cultured with tumor cell lines in the presence of cetuximab or hIgG1 were analyzed for M1/2 surface markers and cytokines. Results: We observed significantly increased monocytic MDSC in non-responders and decreased granulocytic MDSC in responders after cetuximab treatment. In addition, circulating CD11b+CD14+HLA-DRhi monocytes of cetuximab responders displayed attenuated M2 polarization, with decreased CD163+ expression and IL-10 transcripts after cetuximab treatment. This beneficial effect appeared to be FcγR dependent, since CD16 ligation reproduced the reversal of suppressive activity of MDSC in vitro. CD14+ naïve monocytes from the co-cultures of tumor cells, cetuximab and HNSCC patient PBMC or purified monocytes were skewed to an M1-like phenotype, with increased expression of HLA-DR, CD86 and production of IL-12 p70. Likewise, reduced M2 features (expression of CD163 and production of IL-10) were found after crosslinking CD16 on the surface of monocytes to cetuximab-coated tumor cells. Conclusion: Our studies demonstrate a novel function of cetuximab in ameliorating suppressive phenotypes of FcγR bearing myeloid cells in cancer patients, which is associated with better clinical outcome of cetuximab-treated patients. Clinical trial registry: # NCT01218048. Registered 7 October 2010.
date: 2015-11-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28956/1/art%253A10.1186%252Fs40425-015-0097-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28956/7/licence.txt
identifier:   Li, J and Srivastava, RM and Ettyreddy, A and Ferris, RL  (2015) Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients.  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0097-6

relation: http://d-scholarship-dev.library.pitt.edu/27041/
title: 'Lone Wolf' Terrorism and the Classical <i>Jihad</i>: On the Contingencies of Violent Islamic Extremism
creator: Hamoudi, Haider Ala
date: 2015-11-15
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27041/1/Lone%20Wolf%20Terrorism%20and%20the%20Classical%20Jihad-On%20the%20Contingencies%20of%20Violent%20Islamic%20Extremism%20scan.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27041/6/licence.txt
identifier:   Hamoudi, Haider Ala  (2015) 'Lone Wolf' Terrorism and the Classical <i>Jihad</i>: On the Contingencies of Violent Islamic Extremism.         

relation: http://d-scholarship-dev.library.pitt.edu/28958/
title: Genetic contribution of SCARB1 variants to lipid traits in African Blacks: A candidate gene association study
creator: Niemsiri, V
creator: Wang, X
creator: Pirim, D
creator: Radwan, ZH
creator: Bunker, CH
creator: Barmada, MM
creator: Kamboh, MI
creator: Demirci, FY
description: Background: High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria. Methods: We resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits. Results: The initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies ≤1 %) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05). Conclusions: To our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism.
date: 2015-11-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28958/1/art%253A10.1186%252Fs12881-015-0250-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28958/7/licence.txt
identifier:   Niemsiri, V and Wang, X and Pirim, D and Radwan, ZH and Bunker, CH and Barmada, MM and Kamboh, MI and Demirci, FY  (2015) Genetic contribution of SCARB1 variants to lipid traits in African Blacks: A candidate gene association study.  BMC Medical Genetics, 16 (1).       
relation: 10.1186/s12881-015-0250-6

relation: http://d-scholarship-dev.library.pitt.edu/28959/
title: Integrative phenotyping framework (iPF): Integrative clustering of multiple omics data identifies novel lung disease subphenotypes
creator: Kim, SH
creator: Herazo-Maya, JD
creator: Kang, DD
creator: Juan-Guardela, BM
creator: Tedrow, J
creator: Martinez, FJ
creator: Sciurba, FC
creator: Tseng, GC
creator: Kaminski, N
description: Background: The increased multi-omics information on carefully phenotyped patients in studies of complex diseases requires novel methods for data integration. Unlike continuous intensity measurements from most omics data sets, phenome data contain clinical variables that are binary, ordinal and categorical. Results: In this paper we introduce an integrative phenotyping framework (iPF) for disease subtype discovery. A feature topology plot was developed for effective dimension reduction and visualization of multi-omics data. The approach is free of model assumption and robust to data noises or missingness. We developed a workflow to integrate homogeneous patient clustering from different omics data in an agglomerative manner and then visualized heterogeneous clustering of pairwise omics sources. We applied the framework to two batches of lung samples obtained from patients diagnosed with chronic obstructive lung disease (COPD) or interstitial lung disease (ILD) with well-characterized clinical (phenomic) data, mRNA and microRNA expression profiles. Application of iPF to the first training batch identified clusters of patients consisting of homogenous disease phenotypes as well as clusters with intermediate disease characteristics. Analysis of the second batch revealed a similar data structure, confirming the presence of intermediate clusters. Genes in the intermediate clusters were enriched with inflammatory and immune functional annotations, suggesting that they represent mechanistically distinct disease subphenotypes that may response to immunomodulatory therapies. The iPF software package and all source codes are publicly available. Conclusions: Identification of subclusters with distinct clinical and biomolecular characteristics suggests that integration of phenomic and other omics information could lead to identification of novel mechanism-based disease sub-phenotypes.
date: 2015-11-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28959/1/art%253A10.1186%252Fs12864-015-2170-4.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28959/7/licence.txt
identifier:   Kim, SH and Herazo-Maya, JD and Kang, DD and Juan-Guardela, BM and Tedrow, J and Martinez, FJ and Sciurba, FC and Tseng, GC and Kaminski, N  (2015) Integrative phenotyping framework (iPF): Integrative clustering of multiple omics data identifies novel lung disease subphenotypes.  BMC Genomics, 16 (1).       
relation: 10.1186/s12864-015-2170-4

relation: http://d-scholarship-dev.library.pitt.edu/28961/
title: Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy
creator: Kearney, MF
creator: Anderson, EM
creator: Coomer, C
creator: Smith, L
creator: Shao, W
creator: Johnson, N
creator: Kline, C
creator: Spindler, J
creator: Mellors, JW
creator: Coffin, JM
creator: Ambrose, Z
description: Background: Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. Results: A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Conclusions: Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART.
date: 2015-11-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28961/1/art%253A10.1186%252Fs12977-015-0212-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28961/7/licence.txt
identifier:   Kearney, MF and Anderson, EM and Coomer, C and Smith, L and Shao, W and Johnson, N and Kline, C and Spindler, J and Mellors, JW and Coffin, JM and Ambrose, Z  (2015) Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy.  Retrovirology, 12 (1).       
relation: 10.1186/s12977-015-0212-2

relation: http://d-scholarship-dev.library.pitt.edu/26386/
title: Improving the PTP synchronization accuracy under asymmetric delay conditions
creator: Lévesque, M
creator: Tipper, D
description: Tight synchronization timing is expected to play a crucial role for the realization of emerging Internet of Things (IoT) high value real-time applications such as smart transportation and smart grid. Most packet-based synchronization protocols require two-way communications delay symmetry for precise accuracy. The Precision Time Protocol (PTP) provides mechanisms to measure and take into account the delay asymmetry problem, such as the residence time measurements, but recommend PTP support at all nodes. In this paper, we consider partial on-path PTP support, where a subset of the nodes are PTP unaware. We propose probing-based mechanisms in order to estimate asymmetry and improve the synchronization performance. The extensive simulation results show that the proposed lightweight per-packet asymmetry mitigation (PPAM) mechanism, aiming at estimating the per-packet delay components, outperforms the other considered protocols mainly at low to mid network loads, while under certain conditions the regular PTP with QoS support provides more stable synchronization accuracy.
date: 2015-11-10
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26386/1/licence.txt
identifier:   Lévesque, M and Tipper, D  (2015) Improving the PTP synchronization accuracy under asymmetric delay conditions.  IEEE International Symposium on Precision Clock Synchronization for Measurement, Control, and Communication, ISPCS, 2015-N.  88 - 93.  ISSN 1949-0305     
relation: 10.1109/ISPCS.2015.7324689

relation: http://d-scholarship-dev.library.pitt.edu/26385/
title: Protected shortest path visiting specified nodes
creator: Gomes, T
creator: Marques, S
creator: Martins, L
creator: Pascoal, M
creator: Tipper, D
description: In this paper heuristics are proposed for finding the shortest loopless path, from a source node to a target node, that visits a given set of nodes in a directed graph, such that it can be protected using a node-disjoint path. This type of problem may arise due to network management constraints. The problem of calculating the shortest path that visits a given set of nodes is at least as difficult as the traveling salesman problem, and it has not received much attention. Nevertheless an efficient integer linear programming (ILP) formulation has been recently proposed for this problem. Here, the ILP formulation is adapted to include the constraint that the obtained path will be able to be protected by a node-disjoint path. Computational experiments show that this approach, namely in large networks, may fail to obtain a solution in a reasonable amount of time. Therefore three versions of a heuristic are proposed, for which extensive computational results show that they are able to find a solution in most cases, and that the calculated solutions present an acceptable relative error regarding the cost of the optimal active path. Further the CPU time required by the heuristics is significantly smaller than the required by the used ILP solver.
date: 2015-11-10
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26385/1/licence.txt
identifier:   Gomes, T and Marques, S and Martins, L and Pascoal, M and Tipper, D  (2015) Protected shortest path visiting specified nodes.  Proceedings of 2015 7th International Workshop on Reliable Networks Design and Modeling, RNDM 2015.  120 - 127.      
relation: 10.1109/RNDM.2015.7325218

relation: http://d-scholarship-dev.library.pitt.edu/28998/
title: The autism inpatient collection: Methods and preliminary sample description
creator: Siegel, M
creator: Smith, KA
creator: Mazefsky, C
creator: Gabriels, RL
creator: Erickson, C
creator: Kaplan, D
creator: Morrow, EM
creator: Wink, L
creator: Santangelo, SL
description: © 2015 Siegel et al. Background: Individuals severely affected by autism spectrum disorder (ASD), including those with intellectual disability, expressive language impairment, and/or self-injurious behavior (SIB), are underrepresented in the ASD literature and extant collections of phenotypic and biological data. An understanding of ASD's etiology and subtypes can only be as complete as the studied samples are representative. Methods: The Autism Inpatient Collection (AIC) is a multi-site study enrolling children and adolescents with ASD aged 4-20 years admitted to six specialized inpatient psychiatry units. Enrollment began March, 2014, and continues at a rate of over 400 children annually. Measures characterizing adaptive and cognitive functioning, communication, externalizing behaviors, emotion regulation, psychiatric co-morbidity, self-injurious behavior, parent stress, and parent self-efficacy are collected. ASD diagnosis is confirmed by the Autism Diagnostic Observation Schedule - 2 (ADOS-2) and extensive inpatient observation. Biological samples from probands and their biological parents are banked and processed for DNA extraction and creation of lymphoblastoid cell lines. Results: Sixty-one percent of eligible subjects were enrolled. The first 147 subjects were an average of 12.6 years old (SD 3.42, range 4-20); 26.5 % female; 74.8 % Caucasian, and 81.6 % non-Hispanic/non-Latino. Mean non-verbal intelligence quotient IQ = 70.9 (SD 29.16, range 30-137) and mean adaptive behavior composite score = 55.6 (SD 12.9, range 27-96). A majority of subjects (52.4 %) were non- or minimally verbal. The average Aberrant Behavior Checklist - Irritability Subscale score was 28.6, well above the typical threshold for clinically concerning externalizing behaviors, and 26.5 % of the sample engaged in SIB. Females had more frequent and severe SIB than males. Conclusions: Preliminary data indicate that the AIC has a rich representation of the portion of the autism spectrum that is understudied and underrepresented in extant data collections. More than half of the sample is non- or minimally verbal, over 40 % have intellectual disability, and over one quarter exhibit SIB. The AIC is a substantial new resource for study of the full autism spectrum, which will augment existing data on higher-functioning cohorts and facilitate the identification of genetic subtypes and novel treatment targets. The AIC investigators welcome collaborations with other investigators, and access to the AIC phenotypic data and biosamples may be requested through the Simons Foundation (www.sfari.org).
date: 2015-11-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28998/1/art%253A10.1186%252Fs13229-015-0054-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28998/7/licence.txt
identifier:   Siegel, M and Smith, KA and Mazefsky, C and Gabriels, RL and Erickson, C and Kaplan, D and Morrow, EM and Wink, L and Santangelo, SL  (2015) The autism inpatient collection: Methods and preliminary sample description.  Molecular Autism, 6 (1).       
relation: 10.1186/s13229-015-0054-8

relation: http://d-scholarship-dev.library.pitt.edu/28364/
title: An element of determinism in a stochastic flagellar motor switch
creator: Xie, L
creator: Altindal, T
creator: Wu, XL
description: Marine bacterium Vibrio alginolyticus uses a single polar flagellum to navigate in an aqueous environment. Similar to Escherichia coli cells, the polar flagellar motor has two states; when the motor is counter-clockwise, the cell swims forward and when the motor is clockwise, the cell swims backward. V. alginolyticus also incorporates a direction randomization step at the start of the forward swimming interval by flicking its flagellum. To gain an understanding on how the polar flagellar motor switch is regulated, distributions of the forward Δf and backward Δb intervals are investigated herein. We found that the steady-state probability density functions, P(Δf) and P(Δb), of freely swimming bacteria are strongly peaked at a finite time, suggesting that the motor switch is not Poissonian. The short-time inhibition is sufficiently strong and long lasting, i.e., several hundred milliseconds for both intervals, which is readily observed and characterized. Treating motor reversal dynamics as a firstpassage problem, which results from conformation fluctuations of the motor switch, we calculated P(Δf) and P(Δb) and found good agreement with the measurements.
date: 2015-11-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28364/1/journal.pone.0141654.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28364/3/licence.txt
identifier:   Xie, L and Altindal, T and Wu, XL  (2015) An element of determinism in a stochastic flagellar motor switch.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0141654

relation: http://d-scholarship-dev.library.pitt.edu/28366/
title: Expectant mothers maximizing opportunities: Maternal characteristics moderate multifactorial prenatal stress in the prediction of birth weight in a sample of children adopted at birth
creator: Brotnow, L
creator: Reiss, D
creator: Stover, CS
creator: Ganiban, J
creator: Leve, LD
creator: Neiderhiser, JM
creator: Shaw, DS
creator: Stevens, HE
description: Background Mothers' stress in pregnancy is considered an environmental risk factor in child development. Multiple stressors may combine to increase risk, and maternal personal characteristics may offset the effects of stress. This study aimed to test the effect of 1) multifactorial prenatal stress, integrating objective "stressors" and subjective "distress" and 2) the moderating effects of maternal characteristics (perceived social support, self-esteem and specific personality traits) on infant birthweight. Method Hierarchical regression modeling was used to examine cross-sectional data on 403 birth mothers and their newborns from an adoption study. Results Distress during pregnancy showed a statistically significant association with birthweight (R2= 0.032, F(2,398) = 6.782, p = .001). The hierarchical regression model revealed an almost two-fold increase in variance of birthweight predicted by stressors as compared with distress measures (R2Δ = 0.049, F(4,394) = 5.339, p < .001). Further, maternal characteristics moderated this association (R2Δ = 0.031, F(4,389) = 3.413, p = .009). Specifically, the expected benefit to birthweight as a function of higher SES was observed only for mothers with lower levels of harm-avoidance and higher levels of perceived social support. Importantly, the results were not better explained by prematurity, pregnancy complications, exposure to drugs, alcohol or environmental toxins. Conclusions The findings support multidimensional theoretical models of prenatal stress. Although both objective stressors and subjectively measured distress predict birthweight, they should be considered distinct and cumulative components of stress. This study further highlights that jointly considering risk factors and protective factors in pregnancy improves the ability to predict birthweight.
date: 2015-11-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28366/1/journal.pone.0141881.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28366/3/licence.txt
identifier:   Brotnow, L and Reiss, D and Stover, CS and Ganiban, J and Leve, LD and Neiderhiser, JM and Shaw, DS and Stevens, HE  (2015) Expectant mothers maximizing opportunities: Maternal characteristics moderate multifactorial prenatal stress in the prediction of birth weight in a sample of children adopted at birth.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0141881

relation: http://d-scholarship-dev.library.pitt.edu/28365/
title: Merkel cell polyomavirus small t antigen induces cancer and embryonic merkel cell proliferation in a transgenic mouse model
creator: Shuda, M
creator: Guastafierro, A
creator: Geng, X
creator: Shuda, Y
creator: Ostrowski, SM
creator: Lukianov, S
creator: Jenkins, FJ
creator: Honda, K
creator: Maricich, SM
creator: Moore, PS
creator: Chang, Y
description: Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT: Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting.
date: 2015-11-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28365/1/journal.pone.0142329.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28365/3/licence.txt
identifier:   Shuda, M and Guastafierro, A and Geng, X and Shuda, Y and Ostrowski, SM and Lukianov, S and Jenkins, FJ and Honda, K and Maricich, SM and Moore, PS and Chang, Y  (2015) Merkel cell polyomavirus small t antigen induces cancer and embryonic merkel cell proliferation in a transgenic mouse model.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0142329

relation: http://d-scholarship-dev.library.pitt.edu/28999/
title: MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer
creator: Chapman, BV
creator: Wald, AI
creator: Akhtar, P
creator: Munko, AC
creator: Xu, J
creator: Gibson, SP
creator: Grandis, JR
creator: Ferris, RL
creator: Khan, SA
description: Background: Squamous cell carcinoma of the head and neck (SCCHN) remains a prevalent and devastating disease. Recently, there has been an increase in SCCHN cases that are associated with high-risk human papillomavirus (HPV) infection. The clinical characteristics of HPV-positive and HPV-negative SCCHN are known to be different but their molecular features are only recently beginning to emerge. MicroRNAs (miRNAs, miRs) are small, non-coding RNAs that are likely to play significant roles in cancer initiation and progression where they may act as oncogenes or tumor suppressors. Previous studies in our laboratory showed that miR-363 is overexpressed in HPV-positive compared to HPV-negative SCCHN cell lines, and the HPV type 16-E6 oncoprotein upregulates miR-363 in SCCHN cell lines. However, the functional role of miR-363 in SCCHN in the context of HPV infection remains to be elucidated. Methods: We analyzed miR-363 levels in SCCHN tumors with known HPV-status from The Cancer Genome Atlas (TCGA) and an independent cohort from our institution. Cell migration studies were conducted following the overexpression of miR-363 in HPV-negative cell lines. Bioinformatic tools and a luciferase reporter assay were utilized to confirm that miR-363 targets the 3'-UTR of myosin 1B (MYO1B). MYO1B mRNA and protein expression levels were evaluated following miR-363 overexpression in HPV-negative SCCHN cell lines. Small interfering RNA (siRNA) knockdown of MYO1B was performed to assess the phenotypic implication of reduced MYO1B expression in SCCHN cell lines. Results: MiR-363 was found to be overexpressed in HPV-16-positive compared to the HPV-negative SCCHN tumors. Luciferase reporter assays performed in HPV-negative JHU028 cells confirmed that miR-363 targets one of its two potential binding sites in the 3'UTR of MYO1B. MYO1B mRNA and protein levels were reduced upon miR-363 overexpression in four HPV-negative SCCHN cell lines. Increased miR-363 expression or siRNA knockdown of MYO1B expression reduced Transwell migration of SCCHN cell lines, indicating that the miR-363-induced migration attenuation of SCCHN cells may act through MYO1B downregulation. Conclusions: These findings demonstrate that the overexpression of miR-363 reduces cellular migration in head and neck cancer and reveal the biological relationship between miR-363, myosin 1b, and HPV-positive SCCHN.
date: 2015-11-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28999/1/art%253A10.1186%252Fs12885-015-1888-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28999/7/licence.txt
identifier:   Chapman, BV and Wald, AI and Akhtar, P and Munko, AC and Xu, J and Gibson, SP and Grandis, JR and Ferris, RL and Khan, SA  (2015) MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer.  BMC Cancer, 15 (1).       
relation: 10.1186/s12885-015-1888-3

relation: http://d-scholarship-dev.library.pitt.edu/28367/
title: The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration
creator: Sachdev, PS
creator: Lipnicki, DM
creator: Kochan, NA
creator: Crawford, JD
creator: Thalamuthu, A
creator: Andrews, G
creator: Brayne, C
creator: Matthews, FE
creator: Stephan, BCM
creator: Lipton, RB
creator: Katz, MJ
creator: Ritchie, K
creator: Carrière, I
creator: Ancelin, ML
creator: Lam, LCW
creator: Wong, CHY
creator: Fung, AWT
creator: Guaita, A
creator: Vaccaro, R
creator: Davin, A
creator: Ganguli, M
creator: Dodge, H
creator: Hughes, T
creator: Anstey, KJ
creator: Cherbuin, N
creator: Butterworth, P
creator: Ng, TP
creator: Gao, Q
creator: Reppermund, S
creator: Brodaty, H
creator: Schupf, N
creator: Manly, J
creator: Stern, Y
creator: Lobo, A
creator: Lopez-Anton, R
creator: Santabárbara, J
creator: Zimmerman, M
creator: Derby, C
creator: Leung, GTY
creator: Chan, WC
creator: Polito, L
creator: Abbondanza, S
creator: Valle, E
creator: Colombo, M
creator: Vitali, SF
creator: Fossi, S
creator: Zaccaria, D
creator: Forloni, G
creator: Villani, S
creator: Christensen, H
creator: MacKinnon, A
creator: Easteal, S
creator: Jacomb, T
creator: Maxwell, K
creator: Bowman, A
creator: Burns, K
creator: Broe, A
creator: Dekker, J
creator: Dooley, L
creator: De Permentier, M
creator: Fairjones, S
creator: Fletcher, J
creator: French, T
creator: Foster, C
creator: Nugent-Cleary-Fox, E
creator: Gooi, C
creator: Harvey, E
creator: Helyer, R
creator: Hsieh, S
creator: Hughes, L
creator: Jacek, S
creator: Johnston, M
creator: McCade, D
creator: Meeth, S
creator: Milne, E
creator: Moir, A
creator: O'Grady, R
creator: Pfaeffli, K
creator: Pose, C
creator: Reuser, L
creator: Rose, A
creator: Schofield, P
creator: Shahnawaz, Z
creator: Sharpley, A
creator: Thompson, C
creator: Queisser, W
creator: Wong, S
creator: Mayeux, R
creator: Brickman, A
creator: Luchsinger, J
creator: Sanchez, D
creator: Tang, MX
creator: Andrews, H
creator: Marcos, G
creator: De-La-Cámara, C
creator: Saz, P
creator: Ventura, T
creator: Quintanilla, MA
creator: Lobo, E
description: Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.
date: 2015-11-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28367/1/journal.pone.0142388.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28367/3/licence.txt
identifier:   Sachdev, PS and Lipnicki, DM and Kochan, NA and Crawford, JD and Thalamuthu, A and Andrews, G and Brayne, C and Matthews, FE and Stephan, BCM and Lipton, RB and Katz, MJ and Ritchie, K and Carrière, I and Ancelin, ML and Lam, LCW and Wong, CHY and Fung, AWT and Guaita, A and Vaccaro, R and Davin, A and Ganguli, M and Dodge, H and Hughes, T and Anstey, KJ and Cherbuin, N and Butterworth, P and Ng, TP and Gao, Q and Reppermund, S and Brodaty, H and Schupf, N and Manly, J and Stern, Y and Lobo, A and Lopez-Anton, R and Santabárbara, J and Zimmerman, M and Derby, C and Leung, GTY and Chan, WC and Polito, L and Abbondanza, S and Valle, E and Colombo, M and Vitali, SF and Fossi, S and Zaccaria, D and Forloni, G and Villani, S and Christensen, H and MacKinnon, A and Easteal, S and Jacomb, T and Maxwell, K and Bowman, A and Burns, K and Broe, A and Dekker, J and Dooley, L and De Permentier, M and Fairjones, S and Fletcher, J and French, T and Foster, C and Nugent-Cleary-Fox, E and Gooi, C and Harvey, E and Helyer, R and Hsieh, S and Hughes, L and Jacek, S and Johnston, M and McCade, D and Meeth, S and Milne, E and Moir, A and O'Grady, R and Pfaeffli, K and Pose, C and Reuser, L and Rose, A and Schofield, P and Shahnawaz, Z and Sharpley, A and Thompson, C and Queisser, W and Wong, S and Mayeux, R and Brickman, A and Luchsinger, J and Sanchez, D and Tang, MX and Andrews, H and Marcos, G and De-La-Cámara, C and Saz, P and Ventura, T and Quintanilla, MA and Lobo, E  (2015) The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0142388

relation: http://d-scholarship-dev.library.pitt.edu/29002/
title: Remodulation of the tumor microenvironment by regulatory T cells
creator: Liu, Chang
creator: Chikina, Maria D
creator: Workman, Creg J
creator: Vignali, Dario AA
description: The tumor microenvironment is a complex system, which is composed of various types of non-tumor cells including stromal fibroblasts, the blood and lymphatic vascular networks, the extracellular matrix and notably, the infiltrating immune cells. Regulatory T cells (Treg cells) play a pivotal role in tumor malignant progression and contribute to the resistance of tumors to traditional anti-cancer therapies; however, the elimination of Treg cells is not a clinically viable approach, given their crucial role in maintaining immune homeostasis and preventing autoimmunity. Our laboratory has recently reported that Treg-restricted genetic disruption of Neuropilin-1 (Nrp1) selectively induced destabilization of Treg cells within the tumor microenvironment, leading to tumor clearance without inducing autoimmunity. Interestingly, despite of their dramatic tumor-suppressive function, Nrp1-deficient Treg cells are present in tumor in a comparable manner (number and kinetics) to their wild type counterparts, which provides an invaluable research tool to interrogate the function of intratumoral Treg cells without physically removing them and inducing systemic autoimmunity. In this study we aim to systematically investigate the cellular and molecular mediators as well as the underlying mechanisms of Treg-cell function within the tumor microenvironment using a systems biology approach. With the unique Treg-restrictive Nrp1-deficient mice tumor models combined with a multifaceted approach that consists of flow cytometry based immunophenotyping and large-scale transcriptomic profiling, our results indicated that Treg cells act as an early key regulator of tumor immune infiltration and actively induce the global remodulation of the tumor immune transcriptome. Computational deconvolution analysis of the gene profiling data derived from mixed populations further predicted a list of critically modified targets that are regulated at the single cell level. The functional validation of these targets may provide mechanism(s) by which Treg cells interplay with the tumor microenvironment to potentiate tumor growth. This may lead to the development of novel and selective cancer immunotherapies.
publisher: BioMed Central Ltd.
date: 2015-11-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29002/1/art%253A10.1186%252F2051-1426-3-S2-P409.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29002/7/licence.txt
identifier:   Liu, Chang and Chikina, Maria D and Workman, Creg J and Vignali, Dario AA  (2015) Remodulation of the tumor microenvironment by regulatory T cells.  Journal for ImmunoTherapy of Cancer, 3 (P409).   ISSN 2051-1426     

relation: http://d-scholarship-dev.library.pitt.edu/29052/
title: Development of a questionnaire to measure primary care physicians' scope of practice
creator: Ie, K
creator: Ichikawa, S
creator: Takemura, YC
description: Background: Despite an increase in research devoted to primary care attributes, the patient benefits and educational aspects of broad scope practice of primary care physicians (PCPs) have not been well studied, due to a lack of validated measurement in each country. The objective of this study was to develop and validate the Scope of Practice Inventory (SPI) to measure physicians' scope of practice within the Japanese primary care setting. Methods: The questionnaire was developed in seven phases: 1) item generation, 2) consensus method for necessity of each item, 3) Delphi process for the importance of each item, 4) pilot tests to limit the number of items, 5) preliminary cross-sectional study to examine factor structure and to validate the construct validity, 6) evaluation of internal consistency and intra-class reliability, and 7) evaluation of external validity. To confirm the interpretability of the SPI, the determinants of the SPI using a generalized linear model were evaluated. Results: Among 359 items generated by a focus group, 180 reached a defined consensus on face and content validity after the Delphi process. After deletion of items with Kappa values less than 0.6, 120 items were selected for the preliminary study. The principle component analysis using responses from 451 PCPs eliminated 52 items. The final 68-point SPI had three subdomains: Inpatient care, 25 items; Urgent care and minor procedures, 27 items; and Ambulatory care, 16 items. Internal consistency and test-retest reliability for total SPI and each subdomain revealed acceptable reliability. Male sex, less years since graduation, working in a hospital, sub-urban or rural setting, having remote experience, and having board certification as a PCP were positively associated with higher SPI. Conclusions: We developed a self-administered 68-point scale, the SPI, which had satisfactory validity and reliability. Primary care quality and educational research using SPI are expected to contribute to comprehensive and efficient health care systems in the future.
date: 2015-11-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29052/1/art%253A10.1186%252Fs12875-015-0357-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29052/7/licence.txt
identifier:   Ie, K and Ichikawa, S and Takemura, YC  (2015) Development of a questionnaire to measure primary care physicians' scope of practice.  BMC Family Practice, 16 (1).       
relation: 10.1186/s12875-015-0357-z

relation: http://d-scholarship-dev.library.pitt.edu/28587/
title: Medical Student Knowledge of Neglected Tropical Diseases in Peru: A Cross-Sectional Study
creator: Errea, Renato A.
creator: Vasquez-Rios, George
creator: Machicado, Jorge D.
creator: Gallardo, Maria Susana
creator: Cornejo, Marilhia
creator: Urquiaga, Jorge F.
creator: Montoya, Diego
creator: Zamudio, Rodrigo
creator: Terashima, Angelica
creator: Marcos, Luis A.
creator: Samalvides, Frine
contributor: Flisser, Ana
date: 2015-11-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28587/1/journal.pntd.0004197.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28587/3/licence.txt
identifier:   Errea, Renato A. and Vasquez-Rios, George and Machicado, Jorge D. and Gallardo, Maria Susana and Cornejo, Marilhia and Urquiaga, Jorge F. and Montoya, Diego and Zamudio, Rodrigo and Terashima, Angelica and Marcos, Luis A. and Samalvides, Frine  (2015) Medical Student Knowledge of Neglected Tropical Diseases in Peru: A Cross-Sectional Study.  PLOS Neglected Tropical Diseases, 9 (11).  e0004197 - e0004197.      
relation: 10.1371/journal.pntd.0004197

relation: http://d-scholarship-dev.library.pitt.edu/28368/
title: Study on post-treatment relapse in HBeAg positive CHB patients
creator: Lu, J
creator: Li, J
creator: Liu, Y
creator: Ren, S
creator: Cao, Z
creator: Jin, Y
creator: Ma, L
creator: Shen, C
creator: Chen, X
description: Background Many factors are associated with post-treatment relapse in CHB patients, and there are no effective factors to predict relapse. In this study, we investigate the influence factors associated with post-treatment relapse and their predictive value in HBeAg positive CHB (ePCHB). Methods The factors associated with post-treatment relapse were analyzed firstly by a retrospective study in eP-CHB. Variables included age, sex, regimen, baseline HBeAg and HBV DNA level, total course of treatment as well as duration of consolidation therapy after HBeAg seroconversion. The predictive effects of the influence factors were evaluated in an eP-CHB prospective cohort. Results 89 patients were enrolled in the retrospective study, 42(47.2%) relapsed after discontinuation of treatment. Factors related to post-treatment relapse were total course of treatment, duration of consolidation therapy and baseline HBV DNA level. Relapse rates in patients with total course >36 months, consolidation duration >12 months and baseline HBV DNA level < 1.0E+5IU/ml were lower than those of total course <24 months (P = 0.002), consolidation duration ≤1 = 0.01) respectively. Patients with HBV DNA ≥ 1.0E+7IU/ml plus HBeAg<200COI at baseline had the highest relapse rate and cumulative relapse rate than the other three arms (P = 0.048 and 0.008 respectively). Logistic regression analysis demonstrated that baseline HBV DNA level, duration of consolidation therapy and combination of baseline HBV DNA and HBeAg (IgDNA/IgHBeAg) were independent factors to predict posttreatment relapse. The model based on baseline IgDNA/IgHBeAg and consolidation duration worked well in predicting post-treatment relapse in the prospective study and the accuracy, specificity, sensitivity, PPV and NPV for prediction were 80.3%, 81.1%, 79.2%, 73.1%and 85.7% respectively. Conclusions Virological factors including baseline HBV DNA, HBeAg and treatment course were major influence factors associated with post-treatment relapse in eP-CHB. Patients with higher HBV DNA and lower HBeAg levels at baseline, shorter total course as well as consolidation therapy were more likely to develop relapse after discontinuation of therapy. The antiviral therapy in eP-CHB patients should be individually managed at different levels. It is better to treat those with higher viral load and lower HBeAg levels at baseline for a longer course, especially longer consolidation duration so as to decrease the relapse rate.
date: 2015-11-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28368/1/journal.pone.0141072.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28368/3/licence.txt
identifier:   Lu, J and Li, J and Liu, Y and Ren, S and Cao, Z and Jin, Y and Ma, L and Shen, C and Chen, X  (2015) Study on post-treatment relapse in HBeAg positive CHB patients.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0141072

relation: http://d-scholarship-dev.library.pitt.edu/28350/
title: Improved detection of invasive pulmonary aspergillosis arising during leukemia treatment using a panel of host response proteins and fungal antigens
creator: Brasier, AR
creator: Zhao, Y
creator: Spratt, HM
creator: Wiktorowicz, JE
creator: Ju, H
creator: Wheat, LJ
creator: Baden, L
creator: Stafford, S
creator: Wu, Z
creator: Issa, N
creator: Caliendo, AM
creator: Denning, DW
creator: Soman, K
creator: Clancy, CJ
creator: Nguyen, MH
creator: Sugrue, MW
creator: Alexander, BD
creator: Wingard, JR
description: Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment for hematologic malignancy. Upon further validation, early detection of probable IPA in leukemia treatment will provide opportunities for earlier interventions and interventional clinical trials.
date: 2015-11-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28350/1/journal.pone.0143165.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28350/3/licence.txt
identifier:   Brasier, AR and Zhao, Y and Spratt, HM and Wiktorowicz, JE and Ju, H and Wheat, LJ and Baden, L and Stafford, S and Wu, Z and Issa, N and Caliendo, AM and Denning, DW and Soman, K and Clancy, CJ and Nguyen, MH and Sugrue, MW and Alexander, BD and Wingard, JR  (2015) Improved detection of invasive pulmonary aspergillosis arising during leukemia treatment using a panel of host response proteins and fungal antigens.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0143165

relation: http://d-scholarship-dev.library.pitt.edu/28363/
title: Moving in and out of poverty: The within-individual association between socioeconomic status and juvenile delinquency
creator: Rekker, R
creator: Pardini, D
creator: Keijsers, L
creator: Branje, S
creator: Loeber, R
creator: Meeus, W
description: A family's SES can be changeable over time. This study was the first to investigate if such within-individual changes in family SES are associated with parallel fluctuations in boys' delinquent behavior from childhood to adolescence. Participants were a community sample of boys and their caregivers (N = 503) who were assessed annually for ten consecutive years spanning ages 7-18. Fixed effects models revealed that changes in familial SES were related to changes in delinquency: Youths were more likely to offend during years in which their parents' SES was lower than during years in which their parents' SES was higher. Contrary to expectations, we found no evidence that this association was accounted for by families moving to different neighborhoods or by changes in parenting. Since withinindividual models provide a stricter test of causality than between-individual models, these findings support claims that impacting familial SES may have a direct effect on youths' delinquency. Copyright:
date: 2015-11-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28363/1/journal.pone.0136461.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28363/3/licence.txt
identifier:   Rekker, R and Pardini, D and Keijsers, L and Branje, S and Loeber, R and Meeus, W  (2015) Moving in and out of poverty: The within-individual association between socioeconomic status and juvenile delinquency.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0136461

relation: http://d-scholarship-dev.library.pitt.edu/26763/
title: On the use of fixed point theory to design coupled core walls
creator: Eljadei, AA
creator: Harries, KA
description: The use of Fixed Point Theory (FPT) to optimize the design of coupling beams in coupled core wall (CCW) systems is demonstrated. The basis for optimization is minimizing the transmissibility of horizontal ground motion by appropriately linking two coupled wall piers having different dynamic properties with beams having appropriate stiffness and damping characteristics. Using 21 example CCW structures illustrating a range of pier properties, it was shown that the resulting optimization of coupling stiffness is quite small and other design considerations will require stiffer, non-optimal coupling beams. Nonetheless, the potential to leverage the small amount of coupling available in a 'slab-coupled' series of wall piers in order to reduce transmissibility is suggested by the findings of this study.
date: 2015-11-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26763/1/On_The_Use_of_Fixed_Point_Theory_to_Design_Coupled_Core_Walls_Post-Print_Copy.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26763/4/licence.txt
identifier:   Eljadei, AA and Harries, KA  (2015) On the use of fixed point theory to design coupled core walls.  Engineering Structures, 102.  61 - 65.  ISSN 0141-0296     
relation: 10.1016/j.engstruct.2015.07.045

relation: http://d-scholarship-dev.library.pitt.edu/28362/
title: An interactive text message intervention to reduce binge drinking in young adults: A randomized controlled trial with 9-month outcomes
creator: Suffoletto, B
creator: Kristan, J
creator: Chung, T
creator: Jeong, K
creator: Fabio, A
creator: Monti, P
creator: Clark, DB
description: Background Binge drinking is associated with numerous negative consequences. The prevalence and intensity of binge drinking is highest among young adults. This randomized trial tested the efficacy of a 12-week interactive text message intervention to reduce binge drinking up to 6 months after intervention completion among young adults. Methods and Findings Young adult participants (18-25 y; n = 765) drinking above the low-risk limits (AUDIT-C score >3/4 women/men), but not seeking alcohol treatment, were enrolled from 4 Emergency Departments (EDs) in Pittsburgh, PA. Participants were randomized to one of three conditions in a 2:1:1 allocation ratio: SMS Assessments + Feedback (SA+F), SMS Assessments (SA), or control. For 12 weeks, SA+F participants received texts each Thursday querying weekend drinking plans and prompting drinking limit goal commitment and each Sunday querying weekend drinking quantity. SA+F participants received tailored feedback based on their text responses. To contrast the effects of SA+F with self-monitoring, SA participants received texts on Sundays querying drinking quantity, but did not receive alcoholspecific feedback. The control arm received standard care. Follow-up outcome data collected through web-based surveys were provided by 78% of participants at 3- months, 63% at 6-months and 55% at 9-months. Multiple imputation-derived, intent-to-treat models were used for primary analysis. At 9-months, participants in the SA+F group reported greater reductions in the number of binge drinking days than participants in the control group (incident rate ratio [IRR] 0.69; 95% CI .59 to.79), lower binge drinking prevalence (odds ratio [OR] 0.52; 95% CI 0.26 to 0.98]), less drinks per drinking day (beta -.62; 95% CI -1.10 to -0.15) and lower alcohol-related injury prevalence (OR 0.42; 95% CI 0.21 to 0.88). Participants in the SA group did not reduce drinking or alcohol-related injury relative to controls. Findings were similar using complete case analyses. Conclusions An interactive text-message intervention was more effective than self-monitoring or controls in reducing alcohol consumption and alcohol-related injury prevalence up to 6 months after intervention completion. These findings, if replicated, suggest a scalable approach to help achieve sustained reductions in binge drinking and accompanying injuries among young adults.
date: 2015-11-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28362/1/journal.pone.0142877.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28362/3/licence.txt
identifier:   Suffoletto, B and Kristan, J and Chung, T and Jeong, K and Fabio, A and Monti, P and Clark, DB  (2015) An interactive text message intervention to reduce binge drinking in young adults: A randomized controlled trial with 9-month outcomes.  PLoS ONE, 10 (11).       
relation: 10.1371/journal.pone.0142877

relation: http://d-scholarship-dev.library.pitt.edu/28974/
title: Barriers to health care for undocumented immigrants: A literature review
creator: Hacker, K
creator: Anies, M
creator: Folb, BL
creator: Zallman, L
description: With the unprecedented international migration seen in recent years, policies that limit health care access have become prevalent. Barriers to health care for undocumented immigrants go beyond policy and range from financial limitations, to discrimination and fear of deportation. This paper is aimed at reviewing the literature on barriers to health care for undocumented immigrants and identifying strategies that have or could be used to address these barriers. To address study questions, we conducted a literature review of published articles from the last 10 years in PubMed using three main concepts: immigrants, undocumented, and access to health care. The search yielded 341 articles of which 66 met study criteria. With regard to barriers, we identified barriers in the policy arena focused on issues related to law and policy including limitations to access and type of health care. These varied widely across countries but ultimately impacted the type and amount of health care any undocumented immigrant could receive. Within the health system, barriers included bureaucratic obstacles including paperwork and registration systems. The alternative care available (safety net) was generally limited and overwhelmed. Finally, there was evidence of widespread discriminatory practices within the health care system itself. The individual level focused on the immigrant’s fear of deportation, stigma, and lack of capital (both social and financial) to obtain services. Recommendations identified in the papers reviewed included advocating for policy change to increase access to health care for undocumented immigrants, providing novel insurance options, expanding safety net services, training providers to better care for immigrant populations, and educating undocumented immigrants on navigating the system. There are numerous barriers to health care for undocumented immigrants. These vary by country and frequently change. Despite concerns that access to health care attracts immigrants, data demonstrates that people generally do not migrate to obtain health care. Solutions are needed that provide for noncitizens’ health care.
date: 2015-10-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28974/1/rmhp-8-175.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28974/7/licence.txt
identifier:   Hacker, K and Anies, M and Folb, BL and Zallman, L  (2015) Barriers to health care for undocumented immigrants: A literature review.  Risk Management and Healthcare Policy, 8.  175 - 183.      
relation: 10.2147/RMHP.S70173

relation: http://d-scholarship-dev.library.pitt.edu/28369/
title: Deficient and null variants of SERPINA1 are proteotoxic in a Caenorhabditis elegans model of α1-antitrypsin deficiency
creator: Cummings, EE
creator: O'Reilly, LP
creator: King, DE
creator: Silverman, RM
creator: Miedel, MT
creator: Luke, CJ
creator: Perlmutter, DH
creator: Silverman, GA
creator: Pak, SC
description: α1-antitrypsin deficiency (ATD) predisposes patients to both loss-of-function (emphysema) and gain-of-function (liver cirrhosis) phenotypes depending on the type of mutation. Although the Z mutation (ATZ) is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels) or null (<1% normal levels) alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype) induced by the aggregationprone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS), showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gainoffunction proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of different AT variants using a transgenic approach.
date: 2015-10-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28369/1/journal.pone.0141542.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28369/3/licence.txt
identifier:   Cummings, EE and O'Reilly, LP and King, DE and Silverman, RM and Miedel, MT and Luke, CJ and Perlmutter, DH and Silverman, GA and Pak, SC  (2015) Deficient and null variants of SERPINA1 are proteotoxic in a Caenorhabditis elegans model of α1-antitrypsin deficiency.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0141542

relation: http://d-scholarship-dev.library.pitt.edu/29053/
title: The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients
creator: Chen, X
creator: Spaeth, RB
creator: Freeman, SG
creator: Scarborough, MD
creator: Hashmi, JA
creator: Wey, HY
creator: Egorova, N
creator: Vangel, M
creator: Mao, J
creator: Wasan, AD
creator: Edwards, RR
creator: Gollub, RL
creator: Kong, J
description: Recent advances in brain imaging have contributed to our understanding of the neural activity associated with acupuncture treatment. In this study, we investigated functional connectivity across longitudinal acupuncture treatments in older patients with knee osteoarthritis (OA). Over a period of 4 weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before and after their first, third and sixth treatments. Clinical outcome showed a significantly greater pain subscore on the Knee Injury and Osteoarthritis Outcome Score (KOOS) (indicative of improvement) with verum acupuncture than with sham acupuncture. Independent component analysis (ICA) of the resting state fMRI data showed that the right frontoparietal network (rFPN) and the executive control network (ECN) showed enhanced functional connectivity (FC) with the rostral anterior cingulate cortex/medial prefrontal cortex, a key region in the descending pain modulatory system, in the verum groups as compared to the sham group after treatments. We also found that the rFPN connectivity with the left insula is (1) significantly associated with changes in KOOS pain score after treatments, and (2) significantly enhanced after verum acupuncture treatments as compared to sham treatment. Analysis of the acupuncture needle stimulation scan showed that compared with sham treatment, verum acupuncture activated the left operculum/insula, which also overlaps with findings observed in resting state analysis. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by modulating functional connectivity between the rFPN, ECN and the descending pain modulatory pathway. Clinical trial number: NCT01079390
date: 2015-10-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29053/1/art%253A10.1186%252Fs12990-015-0071-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29053/7/licence.txt
identifier:   Chen, X and Spaeth, RB and Freeman, SG and Scarborough, MD and Hashmi, JA and Wey, HY and Egorova, N and Vangel, M and Mao, J and Wasan, AD and Edwards, RR and Gollub, RL and Kong, J  (2015) The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients.  Molecular Pain, 11 (1).  1 - ?.  ISSN 1744-8069     
relation: 10.1186/s12990-015-0071-9

relation: http://d-scholarship-dev.library.pitt.edu/28370/
title: Bidirectional association between self-reported hypertension and gout: The Singapore Chinese health study
creator: Pan, A
creator: Teng, GG
creator: Yuan, JM
creator: Koh, WP
description: It has been hypothesized that the association between hypertension and gout is bidirectional, however, few studies have examined this in a prospective cohort.We analyzed data from the Singapore Chinese Health Study (SCHS) follow-up I (1999-2004) and II (2006-2010) interviews, when both physician-diagnosed hypertension and gout were self-reported. We included participants with data for both follow-up interviews and who were free of heart disease, stroke and cancer at follow-up I. The analysis of hypertension and risk of gout included 31,137 participants when prevalent gout cases were excluded, while the analysis of gout and risk of hypertension included 20,369 participants when prevalent hypertension cases were excluded. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The mean age at follow-up I was 60.1 (SD 7.3) years, and the average follow-up was 6.8 (SD 1.4) years. In the analysis of hypertension and risk of gout, 682 incident cases were identified. Compared to normotensive participants, hypertensive patients had an88% increased risk of developing gout (HR 1.88; 95% CI 1.61-2.21). In the parallel analysis, 5,450 participants reported to have newly diagnosed hypertension during followup. Compared to participants without gout, those with gout had an18% increased risk of developing hypertension (HR 1.18; 95% CI 1.02-1.37). The bidirectional association was stronger in normal weight adults compared to overweight/obese individuals (Pinteraction = 0.06 and 0.04, respectively). The hypertension to gout association was stronger in women compared to men (Pinteraction = 0.04), while the gout to hypertension association was evident in women but not in men (Pinteraction = 0.02). In conclusion, our results suggest that the hypertension-gout association is bidirectional in this cohort of Singapore Chinese adults. The potential interactions of the bidirectional association with obesity and sex deserve further investigations.
date: 2015-10-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28370/1/journal.pone.0141749.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28370/3/licence.txt
identifier:   Pan, A and Teng, GG and Yuan, JM and Koh, WP  (2015) Bidirectional association between self-reported hypertension and gout: The Singapore Chinese health study.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0141749

relation: http://d-scholarship-dev.library.pitt.edu/28371/
title: Unc93b induces apoptotic cell death and is cleaved by host and enteroviral proteases
creator: Harris, KG
creator: Coyne, CB
description: Unc93b is an endoplasmic reticulum (ER)-resident transmembrane protein that serves to bind and traffic toll-like receptors (TLRs) from the ER to their appropriate subcellular locations for ligand sensing. Because of its role in TLR trafficking, Unc93b is necessary for an effective innate immune response to coxsackievirus B3 (CVB), a positive-sense single stranded RNA virus belonging to the enterovirus family. Here, we show that Unc93b is cleaved by a CVB-encoded cysteine protease (3Cpro) during viral replication. Further, we define a role for Unc93b in the induction of apoptotic cell death and show that expression of wild-type Unc93b, but not a mutant incapable of binding TLRs or exiting the ER (H412R), induces apoptosis. Furthermore, we show that cellular caspases activated during apoptosis directly cleave Unc93b. Interestingly, we show that the 3Cpro- and caspase-mediated cleavage of Unc93b both occur within ten amino acids in the distal N-terminus of Unc93b. Mechanistically, neither caspase-mediated nor 3Cpro-mediated cleavage of Unc93b altered its trafficking function, inhibited its role in facilitating TLR3 or TLR8 signaling, or altered its apoptosis- inducing effects. Taken together, our studies show that Unc93b is targeted by both viral- and host cell-specific proteases and identify a function of Unc93b in the induction of apoptotic cell death.
date: 2015-10-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28371/1/journal.pone.0141383.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28371/3/licence.txt
identifier:   Harris, KG and Coyne, CB  (2015) Unc93b induces apoptotic cell death and is cleaved by host and enteroviral proteases.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0141383

relation: http://d-scholarship-dev.library.pitt.edu/29054/
title: Aberrant functioning of the theory-of-mind network in children and adolescents with autism
creator: Kana, RK
creator: Maximo, JO
creator: Williams, DL
creator: Keller, TA
creator: Schipul, SE
creator: Cherkassky, VL
creator: Minshew, NJ
creator: Just, MA
description: Background: Theory-of-mind (ToM), the ability to infer people's thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. Methods: fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two "interacting" geometrical shapes. Results: Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. Conclusions: Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.
date: 2015-10-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29054/1/art%253A10.1186%252Fs13229-015-0052-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29054/7/licence.txt
identifier:   Kana, RK and Maximo, JO and Williams, DL and Keller, TA and Schipul, SE and Cherkassky, VL and Minshew, NJ and Just, MA  (2015) Aberrant functioning of the theory-of-mind network in children and adolescents with autism.  Molecular Autism, 6 (1).       
relation: 10.1186/s13229-015-0052-x

relation: http://d-scholarship-dev.library.pitt.edu/28922/
title: Evaluation of topic-based adaptation and student modeling in QuizGuide
creator: Sosnovsky, S
creator: Brusilovsky, P
description: This paper presents an in-depth analysis of a nonconventional topic-based personalization approach for adaptive educational systems (AES) that we have explored for a number of years in the context of university programming courses. With this approach both student modeling and adaptation are based on coarse-grained knowledge units that we called topics. Our motivation for the topic-based personalization was to enhance AES transparency for both teachers and students by utilizing typical topic-based course structures as the foundation for designing all aspects of an AES from the domain model to the end-user interface. We illustrate the details of the topic-based personalization technology, with the help of the Web-based educational service QuizGuide—the first system to implement it. QuizGuide applies the topic-based personalization to guide students to the right learning material in the context of an undergraduate C programming course. While having a number of architectural and practical advantages, the suggested coarse-grained personalization approach deviates from the common practices toward knowledge modeling in AES. Therefore, we believe that several aspects of QuizGuide required a detailed evaluation—from modeling accuracy to the effectiveness of adaptation. The paper discusses how this new student modeling approach can be evaluated, and presents our attempts to evaluate it from multiple different prospects. The evaluation of QuizGuide across several consecutive semesters demonstrates that, although topics do not always support precise user modeling, they can provide a basis for successful personalization in AESs.
date: 2015-10-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28922/1/umuai_QuizGuide_CR_posted.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28922/7/licence.txt
identifier:   Sosnovsky, S and Brusilovsky, P  (2015) Evaluation of topic-based adaptation and student modeling in QuizGuide.  User Modeling and User-Adapted Interaction, 25 (4).  371 - 424.  ISSN 0924-1868     
relation: 10.1007/s11257-015-9164-4

relation: http://d-scholarship-dev.library.pitt.edu/38905/
title: Comprehension through explanation as the interaction of the brain’s coherence and cognitive control networks
creator: Moss, Jarrod
creator: Schunn, Christian D.
description: Discourse comprehension processes attempt to produce an elaborate and well-connected representation in the reader’s mind. A common network of regions including the angular gyrus, posterior cingulate, and dorsal frontal cortex appears to be involved in constructing coherent representations in a variety of tasks including social cognition tasks, narrative comprehension, and expository text comprehension. Reading strategies that require the construction of explicit inferences are used in the present research to examine how this coherence network interacts with other brain regions. A psychophysiological interaction analysis was used to examine regions showing changed functional connectivity with this coherence network when participants were engaged in either a non-inferencing reading strategy, paraphrasing, or a strategy requiring coherence-building inferences, self-explanation. Results of the analysis show that the coherence network increases in functional connectivity with a cognitive control network that may be specialized for the manipulation of semantic representations and the construction of new relations among these representations.
publisher: Frontiers Media S.A.
date: 2015-10-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/38905/2/fnhum-09-00562.pdf
identifier:   Moss, Jarrod and Schunn, Christian D.  (2015) Comprehension through explanation as the interaction of the brain’s coherence and cognitive control networks.  Frontiers in Human Neuroscience, 9.   ISSN 1662-5161     
relation: https://www.frontiersin.org/articles/10.3389/fnhum.2015.00562/full
relation: 10.3389/fnhum.2015.00562

relation: http://d-scholarship-dev.library.pitt.edu/28372/
title: HMGB1 contributes to the expression of P-Glycoprotein in mouse epileptic brain through toll-like receptor 4 and receptor for advanced glycation end products
creator: Chen, Y
creator: Huang, XJ
creator: Yu, N
creator: Xie, Y
creator: Zhang, K
creator: Wen, F
creator: Liu, H
creator: Di, Q
description: The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1) in the seizure-induced P-glycoprotein (P-gp) overexpression and the underlying mechanism. Kainic acid (KA)-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS) group, KA-induced epileptic seizure (EP) group, and EP group pretreated with HMGB1 (EP +HMGB1 group) or BoxA (HMGB1 antagonist, EP+BoxA group). Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) [toll-like receptor 4 (TLR4) antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE) inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-êB) inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-êB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-êB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene) in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells.
date: 2015-10-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28372/1/journal.pone.0140918.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28372/3/licence.txt
identifier:   Chen, Y and Huang, XJ and Yu, N and Xie, Y and Zhang, K and Wen, F and Liu, H and Di, Q  (2015) HMGB1 contributes to the expression of P-Glycoprotein in mouse epileptic brain through toll-like receptor 4 and receptor for advanced glycation end products.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0140918

relation: http://d-scholarship-dev.library.pitt.edu/28373/
title: In vivo quantification of inflammation in experimental autoimmune encephalomyelitis rats using fluorine-19 magnetic resonance imaging reveals immune cell recruitment outside the nervous system
creator: Zhong, J
creator: Narsinh, K
creator: Morel, PA
creator: Xu, H
creator: Ahrens, ET
description: Progress in identifying new therapies for multiple sclerosis (MS) can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE) rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC) nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.
date: 2015-10-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28373/1/journal.pone.0140238.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28373/3/licence.txt
identifier:   Zhong, J and Narsinh, K and Morel, PA and Xu, H and Ahrens, ET  (2015) In vivo quantification of inflammation in experimental autoimmune encephalomyelitis rats using fluorine-19 magnetic resonance imaging reveals immune cell recruitment outside the nervous system.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0140238

relation: http://d-scholarship-dev.library.pitt.edu/29055/
title: A randomized trial to compare exercise treatment methods for patients after total knee replacement: Protocol paper Rehabilitation, physical therapy and occupational health
creator: Piva, SR
creator: Moore, CG
creator: Schneider, M
creator: Gil, AB
creator: Almeida, GJ
creator: Irrgang, JJ
description: Background: Although the outcome of total knee replacement (TKR) is favorable, surgery alone fails to resolve the functional limitations and physical inactivity that existed prior to surgery. Exercise is likely the only intervention capable of improving these persistent limitations, but exercises have to be performed with intensity sufficient to promote significant changes, at levels that cannot be tolerated until later stages post TKR. The current evidence is limited regarding the effectiveness of exercise at a later stage post TKR. To that end, this study aims to compare the outcomes of physical function and physical activity between 3 treatment groups: clinic-based individual outpatient rehabilitative exercise during 12 weeks, community-based group exercise classes during 12 weeks, and usual medical care (wait-listed control group). The secondary aim is to identify baseline predictors of functional recovery for the exercise groups. Methods/Design: This protocol paper describes a comparative effectiveness study, designed as a 3-group single-blind randomized clinical trial. Two hundred and forty older adults who underwent TKR at least 2 months prior will be randomized into one of the three treatment approaches. Data will be collected at baseline, 3 months, and 6 months. The wait-listed control group will be randomized to one of the 2 exercise groups after 6 months of study participation, and will complete a 9-month follow-up. Primary outcome is physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index Physical Function Subscale (WOMAC-PF). Physical function is also measured by performance-based tests. Secondary outcomes include performance-based tests and physical activity assessed by a patient-reported survey and accelerometry-based physical activity monitors. Exploratory outcomes include adherence, co-interventions, attrition, and adverse events including number of falls. Linear mixed models will be fitted to compare the changes in outcome across groups. Logistic regression will identify patient characteristics that predict functional recovery in the exercise groups. Instrumental variable methods will be used to estimate the efficacy of the interventions in the presence of non-compliance. Discussion: Results will inform recommendations on exercise programs to improve physical function and activity for patients at the later stage post TKR and help tailor interventions according with patients' characteristics. Trial registration: ClinicalTrials.gov Identifier NCT02237911.
date: 2015-10-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29055/1/art%253A10.1186%252Fs12891-015-0761-5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29055/7/licence.txt
identifier:   Piva, SR and Moore, CG and Schneider, M and Gil, AB and Almeida, GJ and Irrgang, JJ  (2015) A randomized trial to compare exercise treatment methods for patients after total knee replacement: Protocol paper Rehabilitation, physical therapy and occupational health.  BMC Musculoskeletal Disorders, 16 (1).       
relation: 10.1186/s12891-015-0761-5

relation: http://d-scholarship-dev.library.pitt.edu/28375/
title: Akt links insulin signaling to albumin endocytosis in proximal tubule epithelial cells
creator: Coffey, S
creator: Costacou, T
creator: Orchard, T
creator: Erkan, E
description: Diabetes mellitus (DM) has become an epidemic, causing a significant decline in quality of life of individuals due to its multisystem involvement. Kidney is an important target organ in DM accounting for the majority of patients requiring renal replacement therapy at dialysis units. Microalbuminuria (MA) has been a valuable tool to predict end-organ damage in DM but its low sensitivity has driven research efforts to seek other alternatives. Albumin is taken up by albumin receptors, megalin and cubilin in the proximal tubule epithelial cells. We demonstrated that insulin at physiological concentrations induce albumin endocytosis through activation of protein kinase B (Akt) in proximal tubule epithelial cells. Inhibition of Akt by a phosphorylation deficient construct abrogated insulin induced albumin endocytosis suggesting a role for Akt in insulin-induced albumin endocytosis. Furthermore we demonstrated a novel interaction between Akt substrate 160kDa (AS160) and cytoplasmic tail of megalin. Mice with type 1 DM (T1D) displayed decreased Akt, megalin, cubilin and AS160 expression in their kidneys in association with urinary cubilin shedding preceding significant MA. Patients with T1D who have developed MA in the EDC (The Pittsburgh Epidemiology of Diabetes Complications) study demonstrated urinary cubilin shedding prior to development of MA. We hypothesize that perturbed insulin-Akt cascade in DM leads to alterations in trafficking of megalin and cubilin, which results in urinary cubilin shedding as a prelude to MA in early diabetic nephropathy. We propose that utilization of urinary cubilin shedding, as a urinary biomarker, will allow us to detect and intervene in diabetic nephropathy (DN) at an earlier stage. Copyright:
date: 2015-10-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28375/1/journal.pone.0140417.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28375/3/licence.txt
identifier:   Coffey, S and Costacou, T and Orchard, T and Erkan, E  (2015) Akt links insulin signaling to albumin endocytosis in proximal tubule epithelial cells.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0140417

relation: http://d-scholarship-dev.library.pitt.edu/28374/
title: Inter-slice blood flow and magnetization transfer effects as a new simultaneous imaging strategy
creator: Han, PK
creator: Barker, JW
creator: Kim, KH
creator: Choi, SH
creator: Bae, KT
creator: Park, SH
description: The recent blood flow and magnetization transfer (MT) technique termed alternate ascending/ descending directional navigation (ALADDIN) achieves the contrast using interslice blood flow and MT effects with no separate preparation RF pulse, thereby potentially overcoming limitations of conventional methods. In this study, we examined the signal characteristics of ALADDIN as a simultaneous blood flow and MT imaging strategy, by comparing it with pseudo-continuous ASL (pCASL) and conventional MT asymmetry (MTA) methods, all of which had the same bSSFP readout. Bloch-equation simulations and experiments showed ALADDIN perfusion signals increased with flip angle, whereas MTA signals peaked at flip angle around 45°-60°. ALADDIN provided signals comparable to those of pCASL and conventional MTA methods emulating the first, second, and third prior slices of ALADDIN under the same scan conditions, suggesting ALADDIN signals to be superposition of signals from multiple labeling planes. The quantitative cerebral blood flow signals from a modified continuous ASL model overestimated the perfusion signals compared to those measured with a pulsed ASL method. Simultaneous mapping of blood flow, MTA, and MT ratio in the whole brain is feasible with ALADDIN within a clinically reasonable time, which can potentially help diagnosis of various diseases.
date: 2015-10-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28374/1/journal.pone.0140560.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28374/3/licence.txt
identifier:   Han, PK and Barker, JW and Kim, KH and Choi, SH and Bae, KT and Park, SH  (2015) Inter-slice blood flow and magnetization transfer effects as a new simultaneous imaging strategy.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0140560

relation: http://d-scholarship-dev.library.pitt.edu/28376/
title: The ML1Nx2 phosphatidylinositol 3,5-bisphosphate probe shows poor selectivity in cells
creator: Hammond, GRV
creator: Takasuga, S
creator: Sasaki, T
creator: Balla, T
description: Phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P2) is a quantitatively minor phospholipid in eukaryotic cells that plays a fundamental role in regulating endocytic membrane traffic. Despite its clear importance for cellular function and organism physiology, mechanistic details of its biology have so far not been fully elucidated. In part, this is due to a lack of experimental tools that specifically probe for PtdIns(3,5)P2 in cells to unambiguously identify its dynamics and site(s) of action. In this study, we have evaluated a recently reported PtdIns(3,5)P2 biosensor, GFP-ML1Nx2, for its veracity as such a probe. We report that, in live cells, the localization of this biosensor to sub-cellular compartments is largely independent of PtdIns(3,5)P2, as assessed after pharmacological, chemical genetic or genomic interventions that block the lipid's synthesis. We therefore conclude that it is unwise to interpret the localization of ML1Nx2 as a true and unbiased biosensor for PtdIns(3,5)P2.
date: 2015-10-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28376/1/journal.pone.0139957.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28376/3/licence.txt
identifier:   Hammond, GRV and Takasuga, S and Sasaki, T and Balla, T  (2015) The ML1Nx2 phosphatidylinositol 3,5-bisphosphate probe shows poor selectivity in cells.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0139957

relation: http://d-scholarship-dev.library.pitt.edu/28377/
title: Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis
creator: Kyrtsos, Christina Rose
creator: Baras, John S.
contributor: Arai, Ken
date: 2015-10-08
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28377/1/journal.pone.0139574.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28377/3/licence.txt
identifier:   Kyrtsos, Christina Rose and Baras, John S.  (2015) Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis.  PLOS ONE, 10 (10).  e0139574 - e0139574.      
relation: 10.1371/journal.pone.0139574

relation: http://d-scholarship-dev.library.pitt.edu/29058/
title: Air toxics and the risk of autism spectrum disorder: The results of a population based case-control study in southwestern Pennsylvania
creator: Talbott, EO
creator: Marshall, LP
creator: Rager, JR
creator: Arena, VC
creator: Sharma, RK
creator: Stacy, SL
description: Background: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. Methods: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N∈=∈224) frequency matched by child's year of birth, sex and race with complete residential histories from prior to pregnancy through the child's second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for mother's age, education, race, smoking status, child's year of birth and sex. Results: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95 % CI∈=∈1.17-3.58, p∈=∈0.013) for the interviewed case-control analysis and 1.61 (95 % CI∈=∈1.08-2.40, p∈=∈0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95 % CI∈=∈1.08-2.38, p∈=∈0.020), which was similarly elevated in the interviewed analysis (OR∈=∈1.52, 95 % CI∈=∈0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR∈=∈1.41, 95 % CI∈=∈0.96-2.07, p∈=∈0.082) and PAHs (OR∈=∈1.44, 95 % CI∈=∈0.98-2.11, p∈=∈0.064). Conclusions: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.
date: 2015-10-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29058/1/art%253A10.1186%252Fs12940-015-0064-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29058/7/licence.txt
identifier:   Talbott, EO and Marshall, LP and Rager, JR and Arena, VC and Sharma, RK and Stacy, SL  (2015) Air toxics and the risk of autism spectrum disorder: The results of a population based case-control study in southwestern Pennsylvania.  Environmental Health: A Global Access Science Source, 14 (1).       
relation: 10.1186/s12940-015-0064-1

relation: http://d-scholarship-dev.library.pitt.edu/29057/
title: Ether in the developing world: rethinking an abandoned agent.
creator: Chang, Connie Y
creator: Goldstein, Elisabeth
creator: Agarwal, Nitin
creator: Swan, Kenneth G
description: BACKGROUND: The first true demonstration of ether as an inhalation anesthetic was on October 16, 1846 by William T.G. Morton, a Boston dentist. Ether has been replaced completely by newer inhalation agents and open drop delivery systems have been exchanged for complicated vaporizers and monitoring systems. Anesthesia in the developing world, however, where lack of financial stability has halted the development of the field, still closely resembles primitive anesthetics. DISCUSSION: In areas where resources are scarce, patients are often not given supplemental intraoperative analgesia. While halothane provides little analgesia, ether provides excellent intra-operative pain control that can extend for several hours into the postoperative period. An important barrier to the widespread use of ether is availability. With decreasing demand, production of the inexpensive inhalation agent has fallen. Ether is inexpensive to manufacture, and encouraging increased production at a local level would help developing nations to cut costs and become more self-sufficient.
date: 2015-10-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29057/1/art%253A10.1186%252Fs12871-015-0128-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29057/7/licence.txt
identifier:   Chang, Connie Y and Goldstein, Elisabeth and Agarwal, Nitin and Swan, Kenneth G  (2015) Ether in the developing world: rethinking an abandoned agent.  BMC Anesthesiol, 15.  149 - ?.      
relation: 10.1186/s12871-015-0128-3
language: eng

relation: http://d-scholarship-dev.library.pitt.edu/29060/
title: SLC39A6: A potential target for diagnosis and therapy of esophageal carcinoma
creator: Cui, XB
creator: Shen, YY
creator: Jin, TT
creator: Li, S
creator: Li, TT
creator: Zhang, SM
creator: Peng, H
creator: Liu, CX
creator: Li, SG
creator: Yang, L
creator: Li, N
creator: Hu, JM
creator: Jiang, JF
creator: Li, M
creator: Liang, WH
creator: Li, Y
creator: Wei, YT
creator: Sun, ZZ
creator: Wu, CY
creator: Chen, YZ
creator: Li, F
description: Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC. Methods: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied. Results: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro. Conclusions: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.
date: 2015-10-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29060/1/art%253A10.1186%252Fs12967-015-0681-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29060/7/licence.txt
identifier:   Cui, XB and Shen, YY and Jin, TT and Li, S and Li, TT and Zhang, SM and Peng, H and Liu, CX and Li, SG and Yang, L and Li, N and Hu, JM and Jiang, JF and Li, M and Liang, WH and Li, Y and Wei, YT and Sun, ZZ and Wu, CY and Chen, YZ and Li, F  (2015) SLC39A6: A potential target for diagnosis and therapy of esophageal carcinoma.  Journal of Translational Medicine, 13 (1).       
relation: 10.1186/s12967-015-0681-z

relation: http://d-scholarship-dev.library.pitt.edu/29059/
title: Temporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch
creator: Venkatachari, NJ
creator: Zerbato, JM
creator: Jain, S
creator: Mancini, AE
creator: Chattopadhyay, A
creator: Sluis-Cremer, N
creator: Bar-Joseph, Z
creator: Ayyavoo, V
description: Background: Latent HIV-1 reservoirs are identified as one of the major challenges to achieve HIV-1 cure. Currently available strategies are associated with wide variability in outcomes both in patients and CD4+ T cell models. This underlines the critical need to develop innovative strategies to predict and recognize ways that could result in better reactivation and eventual elimination of latent HIV-1 reservoirs. Results and discussion: In this study, we combined genome wide transcriptome datasets post activation with Systems Biology approach (Signaling and Dynamic Regulatory Events Miner, SDREM analyses) to reconstruct a dynamic signaling and regulatory network involved in reactivation mediated by specific activators using a latent cell line. This approach identified several critical regulators for each treatment, which were confirmed in follow-up validation studies using small molecule inhibitors. Results indicate that signaling pathways involving JNK and related factors as predicted by SDREM are essential for virus reactivation by suberoylanilide hydroxamic acid. ERK1/2 and NF-κB pathways have the foremost role in reactivation with prostratin and TNF-aα, respectively. JAK-STAT pathway has a central role in HIV-1 transcription. Additional evaluation, using other latent J-Lat cell clones and primary T cell model, also confirmed that many of the cellular factors associated with latency reversing agents are similar, though minor differences are identified. JAK-STAT and NF-κB related pathways are critical for reversal of HIV-1 latency in primary resting T cells. Conclusion: These results validate our combinatorial approach to predict the regulatory cellular factors and pathways responsible for HIV-1 reactivation in latent HIV-1 harboring cell line models. JAK-STAT have a role in reversal of latency in all the HIV-1 latency models tested, including primary CD4+ T cells, with additional cellular pathways such as NF-κB, JNK and ERK 1/2 that may have complementary role in reversal of HIV-1 latency.
date: 2015-10-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29059/1/art%253A10.1186%252Fs12977-015-0211-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29059/7/licence.txt
identifier:   Venkatachari, NJ and Zerbato, JM and Jain, S and Mancini, AE and Chattopadhyay, A and Sluis-Cremer, N and Bar-Joseph, Z and Ayyavoo, V  (2015) Temporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch.  Retrovirology, 12 (1).       
relation: 10.1186/s12977-015-0211-3

relation: http://d-scholarship-dev.library.pitt.edu/28378/
title: A comparison of free-standing versus co-located long-term acute care hospitals
creator: Kahn, JM
creator: Barnato, AE
creator: Lave, JR
creator: Pike, F
creator: Weissfeld, LA
creator: Le, TQ
creator: Angus, DC
creator: Gold, JA
description: Background Long-term acute care hospitals (LTACs) provide specialized treatment for patients with chronic critical illness. Increasingly LTACs are co-located within traditional short-stay hospitals rather than operated as free-standing facilities, which may affect LTAC utilization patterns and outcomes. Methods We compared free-standing and co-located LTACs using 2005 data from the United States Centers for Medicare & Medicaid Services. We used bivariate analyses to examine patient characteristics and timing of LTAC transfer, and used propensity matching and multivariable regression to examine mortality, readmissions, and costs after transfer. Results Of 379 LTACs in our sample, 192 (50.7%) were free-standing and 187 (49.3%) were co-located in a short-stay hospital. Co-located LTACs were smaller (median bed size: 34 vs. 66, p <0.001) and more likely to be for-profit (72.2% v. 68.8%, p = 0.001) than freestanding LTACs. Co-located LTACs admitted patients later in their hospital course (average time prior to transfer: 15.5 days vs. 14.0 days) and were more likely to admit patients for ventilator weaning (15.9% vs. 12.4%). In the multivariate propensity-matched analysis, patients in co-located LTACs experienced higher 180-day mortality (adjusted relative risk: 1.05, 95% CI: 1.00-1.11, p = 0.04) but lower readmission rates (adjusted relative risk: 0.86, 95% CI: 0.75-0.98, p = 0.02). Costs were similar between the two hospital types (mean difference in costs within 180 days of transfer: -$3,580, 95% CI: -$8,720 -$1,550, p = 0.17). Conclusions Compared to patients in free-standing LTACs, patients in co-located LTACs experience slightly higher mortality but lower readmission rates, with no change in overall resource use as measured by 180 day costs.
date: 2015-10-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28378/1/journal.pone.0139742.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28378/3/licence.txt
identifier:   Kahn, JM and Barnato, AE and Lave, JR and Pike, F and Weissfeld, LA and Le, TQ and Angus, DC and Gold, JA  (2015) A comparison of free-standing versus co-located long-term acute care hospitals.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0139742

relation: http://d-scholarship-dev.library.pitt.edu/29136/
title: Alveolar macrophages support interferon gamma-mediated viral clearance in RSVinfected neonatal mice
creator: Eichinger, KM
creator: Egaña, L
creator: Orend, JG
creator: Resetar, E
creator: Anderson, KB
creator: Patel, R
creator: Empey, KM
description: Background: Poor interferon gamma (IFNγ) production during respiratory syncytial virus (RSV) is associated with prolonged viral clearance and increased disease severity in neonatal mice and humans. We previously showed that intra-nasal delivery of IFNγ significantly enhances RSV clearance from neonatal lungs prior to observed T-lymphocyte recruitment or activation, suggesting an innate immune mechanism of viral clearance. We further showed that alveolar macrophages dominate the RSV-infected neonatal airways relative to adults, consistent with human neonatal autopsy data. Therefore, the goal of this work was to determine the role of neonatal alveolar macrophages in IFNγ-mediated RSV clearance. Methods: Clodronate liposomes, flow cytometry, viral plaque assays, and histology were used to examine the role of alveolar macrophages (AMs) and the effects of intra-nasal IFNγ in RSV infected neonatal Balb/c mice. The functional outcomes of AM depletion were determined quantitatively by viral titers using plaque assay. Illness was assessed by measuring reduced weight gain. Results: AM activation during RSV infection was age-dependent and correlated tightly with IFNγ exposure. Higher doses of IFNγ more efficiently stimulated AM activation and expedited RSV clearance without significantly affecting weight gain. The presence of AMs were independently associated with improved RSV clearance, whereas AM depletion but not IFNγ exposure, significantly impaired weight gain in RSV-infected neonates. Conclusion: We show here for the first time, that IFNγ is critical for neonatal RSV clearance and that it depends, in part, on alveolar macrophages (AMs) for efficient viral clearing effects. Early reductions in viral burden are likely to have profound short- and long-term immune effects in the vulnerable post-natally developing lung environment. Studies are ongoing to elucidate the pathologic effects associated with early versus delayed RSV clearance in developing neonatal airways.
date: 2015-10-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29136/1/art%253A10.1186%252Fs12931-015-0282-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29136/7/licence.txt
identifier:   Eichinger, KM and Egaña, L and Orend, JG and Resetar, E and Anderson, KB and Patel, R and Empey, KM  (2015) Alveolar macrophages support interferon gamma-mediated viral clearance in RSVinfected neonatal mice.  Respiratory Research, 16 (1).   ISSN 1465-9921     
relation: 10.1186/s12931-015-0282-7

relation: http://d-scholarship-dev.library.pitt.edu/29138/
title: Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma
creator: Beumer, JH
creator: Fu, KY
creator: Anyang, BN
creator: Siegfried, JM
creator: Bakkenist, CJ
description: Background: ATM and ATR are kinases implicated in a myriad of DNA-damage responses. ATM kinase inhibition radiosensitizes cells and selectively kills cells with Fanconi anemia (FA) gene mutations. ATR kinase inhibition sensitizes cells to agents that induce replication stress and selectively kills cells with ATM and TP53 mutations. ATM mutations and FANCF promoter-methylation are reported in lung carcinomas. Methods: We undertook functional analyses of ATM, ATR, Chk1 and FA proteins in lung cancer cell lines. We included Calu6 that is reported to be FANCL-deficient. In addition, the cancer genome atlas (TCGA) database was interrogated for alterations in: 1) ATM, MRE11A, RAD50 and NBN; 2) ATR, ATRIP and TOPBP1; and 3) 15 FA genes. Results: No defects in ATM, ATR or Chk1 kinase activation, or FANCD2 monoubiquitination were identified in the lung cancer cell lines examined, including Calu6, and major alterations in these pathways were not identified in the TCGA database. Cell lines were radiosensitized by ATM kinase inhibitor KU60019, but no cell killing by ATM kinase inhibitor alone was observed. While no synergy between gemcitabine or carboplatin and ATR kinase inhibitor ETP-46464 was observed, synergy between gemcitabine and Chk1 kinase inhibitor UCN-01 was observed in 54T, 201T and H460, and synergy between carboplatin and Chk1 kinase inhibitor was identified in 201T and 239T. No interactions between ATM, ATR and FA activation were observed by either ATM or ATR kinase inhibition in the lung cancer cell lines. Conclusions: Analyses of ATM serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination revealed that ATM and ATR kinase activation and FA pathway signaling are intact in the lung cancer cell lines examined. As such, these posttranslational modifications may have utility as biomarkers for the integrity of DNA damage signaling pathways in lung cancer. Different sensitization profiles between gemcitabine and carboplatin and ATR kinase inhibitor ETP-46464 and Chk1 kinase inhibitor UCN-01 were observed and this should be considered in the rationale for Phase I clinical trial design with ATR kinase inhibitors.
date: 2015-10-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29138/1/art%253A10.1186%252Fs12885-015-1649-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29138/7/licence.txt
identifier:   Beumer, JH and Fu, KY and Anyang, BN and Siegfried, JM and Bakkenist, CJ  (2015) Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma.  BMC Cancer, 15 (1).       
relation: 10.1186/s12885-015-1649-3

relation: http://d-scholarship-dev.library.pitt.edu/28380/
title: Definitive characterization of CA 19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimens
creator: Haab, BB
creator: Huang, Y
creator: Balasenthil, S
creator: Partyka, K
creator: Tang, H
creator: Anderson, M
creator: Allen, P
creator: Sasson, A
creator: Zeh, H
creator: Kaul, K
creator: Kletter, D
creator: Ge, S
creator: Bern, M
creator: Kwon, R
creator: Blasutig, I
creator: Srivastava, S
creator: Frazier, ML
creator: Sen, S
creator: Hollingsworth, MA
creator: Rinaudo, JA
creator: Killary, AM
creator: Brand, RE
description: The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.
date: 2015-10-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28380/1/journal.pone.0139049.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28380/3/licence.txt
identifier:   Haab, BB and Huang, Y and Balasenthil, S and Partyka, K and Tang, H and Anderson, M and Allen, P and Sasson, A and Zeh, H and Kaul, K and Kletter, D and Ge, S and Bern, M and Kwon, R and Blasutig, I and Srivastava, S and Frazier, ML and Sen, S and Hollingsworth, MA and Rinaudo, JA and Killary, AM and Brand, RE  (2015) Definitive characterization of CA 19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimens.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0139049

relation: http://d-scholarship-dev.library.pitt.edu/28379/
title: Effects of citalopram on sutural and calvarial cell processes
creator: Durham, E
creator: Jen, S
creator: Wang, L
creator: Nasworthy, J
creator: Elsalanty, M
creator: Weinberg, S
creator: Yu, J
creator: Cray, J
description: The use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression during pregnancy is suggested to increase the incidence of craniofacial abnormalities including craniosynostosis. Little is known about this mechanism, however based on previous data we propose a mechanism that affects cell cycle. Excessive proliferation, and reduction in apoptosis may lead to hyperplasia within the suture that may allow for differentiation, bony infiltration, and fusion. Here we utilized in vivo and in vitro analysis to investigate this proposed phenomenon. For in vivo analysis we used C57BL-6 wild-type breeders treated with a clinical dose of citalopram during the third trimester of pregnancy to produce litters exposed to the SSRI citalopram in utero. At post-natal day 15 sutures were harvested from resulting pups and subjected to histomorphometric analysis for proliferation (PCNA) and apoptosis (TUNEL). For in vitro studies, we used mouse calvarial pre-osteoblast cells (MC3T3-E1) to assess proliferation (MTS), apoptosis (Caspase 3/7-activity), and gene expression after exposure to titrated doses of citalopram. In vivo analysis for PCNA suggested segregation of effect by location, with the sagittal suture, showing a statistically significant increase in proliferative response. The coronal suture was not similarly affected, however there was a decrease in apoptotic activity at the dural edge as compared to the periosteal edge. No differences in apoptosis by suture or area due to SSRI exposure were observed. In vitro results suggest citalopram exposure increased proliferation and proliferative gene expression, and decreased apoptosis of the MC3T3-E1 cells. Decreased apoptosis was not confirmed in vivo however, an increase in proliferation without a concomitant increase in apoptosis is still defined as hyperplasia. Thus prenatal SSRI exposure may exert a negative effect on post-natal growth through a hyperplasia effect at the cranial growth sites perhaps leading to clinically significant craniofacial abnormalities. Copyright:
date: 2015-10-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28379/1/journal.pone.0139719.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28379/3/licence.txt
identifier:   Durham, E and Jen, S and Wang, L and Nasworthy, J and Elsalanty, M and Weinberg, S and Yu, J and Cray, J  (2015) Effects of citalopram on sutural and calvarial cell processes.  PLoS ONE, 10 (10).       
relation: 10.1371/journal.pone.0139719

relation: http://d-scholarship-dev.library.pitt.edu/25519/
title: Library Automation: Core Concepts and Practical Systems Analysis. 3rd ed
creator: Tomer, Christinger
publisher: Informa UK Limited
date: 2015-10-02
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25519/1/licence.txt
identifier:   Tomer, Christinger  (2015) Library Automation: Core Concepts and Practical Systems Analysis. 3rd ed.  Technical Services Quarterly, 32 (4).  467 - 469.  ISSN 0731-7131     
relation: 10.1080/07317131.2015.1059708
language: en

relation: http://d-scholarship-dev.library.pitt.edu/27039/
title: Sex and the Shari’a: Defining Gender Norms and Sexual Deviancy in Shi’i Islam
creator: Hamoudi, Haider Ala
date: 2015-10-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27039/1/Sex%20Sharia.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27039/7/licence.txt
identifier:   Hamoudi, Haider Ala  (2015) Sex and the Shari’a: Defining Gender Norms and Sexual Deviancy in Shi’i Islam.         

relation: http://d-scholarship-dev.library.pitt.edu/26289/
title: Storytelling with a wink and a smile: the arrival of the Emoji-pocalypse
creator: Collister, Lauren Brittany
description: Whether you view them as a scourge or a convenience, emoji are ubiquitous in online communication. In celebration of the power of the emoji, the National Young Writers' Festival is soliciting submissions for emoji stories for this year’s festival.
date: 2015-10-01
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26289/1/licence.txt
identifier:   Collister, Lauren Brittany  (2015) Storytelling with a wink and a smile: the arrival of the Emoji-pocalypse.         
relation: https://theconversation.com/storytelling-with-a-wink-and-a-smile-the-arrival-of-the-emoji-pocalypse-48308

relation: http://d-scholarship-dev.library.pitt.edu/29139/
title: The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831
creator: Perez, EA
creator: Baehner, FL
creator: Butler, SM
creator: Thompson, EA
creator: Dueck, AC
creator: Jamshidian, F
creator: Cherbavaz, D
creator: Yoshizawa, C
creator: Shak, S
creator: Kaufman, PA
creator: Davidson, NE
creator: Gralow, J
creator: Asmann, YW
creator: Ballman, KV
description: Introduction: The N9831 trial demonstrated the efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) locally positive tumors by protein or gene analysis. We used the 21-gene assay to examine the association of quantitative HER2 messenger RNA (mRNA) gene expression and benefit from trastuzumab. Methods: N9831 tested the addition of trastuzumab to chemotherapy in stage I-III HER2-positive breast cancer. For two of the arms of the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA expression were determined by the 21-gene assay (Oncotype DX®) (negative <10.7, equivocal 10.7 to <11.5, and positive ≥11.5 log<inf>2</inf> expression units). Cox regression was used to assess the association of HER2 expression with trastuzumab benefit in preventing distant recurrence. Results: Median follow-up was 7.4years. Of 1,940 total patients, 901 had consent and sufficient tissue. HER2 by reverse transcriptase polymerase chain reaction (RT-PCR) was negative in 130 (14%), equivocal in 85 (9%), and positive in 686 (76%) patients. Concordance between HER2 assessments was 95% for RT-PCR versus central immunohistochemistry (IHC) (>10% positive cells = positive), 91% for RT-PCR versus central fluorescence in situ hybridization (FISH) (≥2.0 = positive) and 94% for central IHC versus central FISH. In the primary analysis, the association of HER2 expression by 21-gene assay with trastuzumab benefit was marginally nonsignificant (nonlinear p = 0.057). In hormone receptor-positive patients (local IHC) the association was significant (p = 0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 expression levels. Conclusions: Concordance among HER2 assessments by central IHC, FISH, and RT-PCR were similar and high. Association of HER2 mRNA expression with trastuzumab benefit as measured by time to distant recurrence was nonsignificant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in patients with either IHC-positive or FISH-positive tumors. Trend for benefit was observed also for the small groups of patients with negative results by any or all of the central assays. Trial registration: Clinicaltrials.gov NCT00005970. Registered 5 July 2000.
date: 2015-10-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29139/1/art%253A10.1186%252Fs13058-015-0643-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29139/7/licence.txt
identifier:   Perez, EA and Baehner, FL and Butler, SM and Thompson, EA and Dueck, AC and Jamshidian, F and Cherbavaz, D and Yoshizawa, C and Shak, S and Kaufman, PA and Davidson, NE and Gralow, J and Asmann, YW and Ballman, KV  (2015) The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831.  Breast Cancer Research, 17 (1).   ISSN 1465-5411     
relation: 10.1186/s13058-015-0643-7

relation: http://d-scholarship-dev.library.pitt.edu/29140/
title: Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma
creator: Tarhini, AA
creator: Zahoor, H
creator: Yearley, JH
creator: Gibson, C
creator: Rahman, Z
creator: Dubner, R
creator: Rao, UNM
creator: Sander, C
creator: Kirkwood, JM
description: Background: Characterization of PD-L1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes (SLN) is important to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy. Methods: Patients included had primary cutaneous melanoma, Breslow thickness of 2.01-4.0 or >4mm with or without tumor ulceration (T3a, T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. The slides were separately evaluated by two pathologists (JY and CG). Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral and peritumoral locations, by utilizing two scoring methods. Results: Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by H&E review of the cut sections were included in the final analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2mm. For three patients, the melanin content was too high to confidently assign a PD-L1 score. For the remaining 21 patients, all had some evidence of either intratumoral or peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD-L1 expression was: 0% of tumor cells (3pts, 14%); <1% (5pts, 24%); 1-10% (6pts, 29%) and >10% (7pts, 33%). Conclusions: Tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN of the majority of patients. These results support the testing of a therapeutic role for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma micrometastases.
date: 2015-09-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29140/1/art%253A10.1186%252Fs12967-015-0678-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29140/7/licence.txt
identifier:   Tarhini, AA and Zahoor, H and Yearley, JH and Gibson, C and Rahman, Z and Dubner, R and Rao, UNM and Sander, C and Kirkwood, JM  (2015) Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma.  Journal of Translational Medicine, 13 (1).       
relation: 10.1186/s12967-015-0678-7

relation: http://d-scholarship-dev.library.pitt.edu/29142/
title: Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma
creator: Pradhan, D
creator: Roy, S
creator: Quiroga-Garza, G
creator: Cieply, K
creator: Mahaffey, AL
creator: Bastacky, S
creator: Dhir, R
creator: Parwani, AV
description: Background: Xp11.2 or TFE3 translocation renal cell carcinomas (RCC) and alveolar soft part sarcoma (ASPS) are characterized by chromosome translocations involving the Xp11.2 breakpoint resulting in transcription factor TFE3 gene fusions. The most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or ASPL respectively. TFE3 immunohistochemistry (IHC) has been inconsistent over time due to background staining problems in part related to fixation issues. Karyotyping to detect TFE3 gene rearrangement requires typically unavailable fresh tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) is generally very challenging due to degradation of RNA in archival material. The study objective was to develop and validate a TFE3 break-apart fluorescence in situ hybridization (FISH) assay to confirm Xp11 translocation RCCs and ASPS. Methods: Representative sections of formalin-fixed paraffin-embedded tissue blocks were selected in 40 possible cases. Approximately 60 tumor cells were analyzed in the targeted region. The validation of TFE3 FISH was done with 11 negative and two positive cases. Cut off for a positive result was validated as >7.15 % positive nuclei with any pattern of break-apart signals. FISH evaluation was done blinded of the immunohistochemical or karyotype data. Results: Three out of forty cases were positive for the TFE3 break-apart signals by FISH. The negative cases were reported as clear cell RCC with papillary features (10), clear cell RCC with sarcomatoid areas (2), Papillary RCC with clear cell areas (9), Chromophobe RCC (2), RCC, unclassified type (3) and renal medullary carcinoma (1). 3 of the negative cases were consultation cases for renal tumor with unknown histology. Seven negative cases were soft tissue tumor suspicious for ASPS. Conclusion: Our study validates the utility of TFE3 break-apart FISH on formalin-fixed paraffin-embedded tissue sections for diagnosis and confirmation of Xp11.2 translocation RCCs and ASPS.
date: 2015-09-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29142/1/art%253A10.1186%252Fs13000-015-0412-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29142/7/licence.txt
identifier:   Pradhan, D and Roy, S and Quiroga-Garza, G and Cieply, K and Mahaffey, AL and Bastacky, S and Dhir, R and Parwani, AV  (2015) Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma.  Diagnostic Pathology, 10 (1).       
relation: 10.1186/s13000-015-0412-z

relation: http://d-scholarship-dev.library.pitt.edu/26821/
title: Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats
creator: Zheng, H
creator: Stornetta, RL
creator: Agassandian, K
creator: Rinaman, L
description: The expression of a vesicular glutamate transporter (VGLUT) suffices to assign a glutamatergic phenotype to neurons and other secretory cells. For example, intestinal L cells express VGLUT2 and secrete glutamate along with glucagon-like peptide 1 (GLP1). We hypothesized that GLP1-positive neurons within the caudal (visceral) nucleus of the solitary tract (cNST) also are glutamatergic. To test this, the axonal projections of GLP1 and other neurons within the cNST were labeled in rats via iontophoretic delivery of anterograde tracer. Dual immunofluorescence and confocal microscopy was used to visualize tracer-, GLP1-, and VGLUT2-positive fibers within brainstem, hypothalamic, and limbic forebrain nuclei that receive input from the cNST. Electron microscopy was used to confirm GLP1 and VGLUT2 immunolabeling within the same axon varicosities, and fluorescent in situ hybridization was used to examine VGLUT2 mRNA expression by GLP1-positive neurons. Most anterograde tracer-labeled fibers displayed VGLUT2-positive varicosities, providing new evidence that ascending axonal projections from the cNST are primarily glutamatergic. Virtually all GLP1-positive varicosities also were VGLUT2-positive. Electron microscopy confirmed the colocalization of GLP1 and VGLUT2 immunolabeling in axon terminals that formed asymmetric (excitatory-type) synapses with unlabeled dendrites in the hypothalamus. Finally, in situ hybridization confirmed that GLP1-positive cNST neurons express VGLUT2 mRNA. Thus, hindbrain GLP1 neurons in rats are equipped to store glutamate in synaptic vesicles, and likely co-release both glutamate and GLP1 from axon varicosities and terminals in the hypothalamus and other brain regions.
date: 2015-09-28
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26821/1/licence.txt
identifier:   Zheng, H and Stornetta, RL and Agassandian, K and Rinaman, L  (2015) Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats.  Brain Structure and Function, 220 (5).  3011 - 3022.  ISSN 1863-2653     
relation: 10.1007/s00429-014-0841-6

relation: http://d-scholarship-dev.library.pitt.edu/29143/
title: Protocol for a statewide randomized controlled trial to compare three training models for implementing an evidence-based treatment
creator: Herschell, AD
creator: Kolko, DJ
creator: Scudder, AT
creator: Taber-Thomas, S
creator: Schaffner, KF
creator: Hiegel, SA
creator: Iyengar, S
creator: Chaffin, M
creator: Mrozowski, S
description: Background: Evidence-based treatments (EBTs) are available for treating childhood behavioral health challenges. Despite EBTs' potential to help children and families, they have primarily remained in university settings. Little empirical evidence exists regarding how specific, commonly used training and quality control models are effective in changing practice, achieving full implementation, and supporting positive client outcomes. Methods/design: This study (NIMH RO1 MH095750; ClinicalTrials.gov Identifier: NCT02543359), which is currently in progress, will evaluate the effectiveness of three training models (Learning Collaborative (LC), Cascading Model (CM), and Distance Education (DE)) to implement a well-established EBT , Parent-Child Interaction Therapy, in real-world, community settings. The three models differ in their costs, skill training, quality control methods, and capacity to address broader implementation challenges. The project is guided by three specific aims: (1) to build knowledge about training outcomes, (2) to build knowledge about implementation outcomes, and (3) to test the differential impact of training clinicians using LC, CM, and DE models on key client outcomes. Fifty (50) licensed psychiatric clinics across Pennsylvania were randomized to one of the three training conditions: (1) LC, (2) CM, or (3) DE. The impact of training on practice skills (clinician level) and implementation/sustainment outcomes (clinic level) are being evaluated at four timepoints coinciding with the training schedule: baseline, 6 (mid), 12 (post), and 24 months (1 year follow-up). Immediately after training begins, parent-child dyads (client level) are recruited from the caseloads of participating clinicians. Client outcomes are being assessed at four timepoints (pre-treatment, 1, 6, and 12 months after the pre-treatment). Discussion: This proposal builds on an ongoing initiative to implement an EBT statewide. A team of diverse stakeholders including state policy makers, payers, consumers, service providers, and academics from different, but complementary areas (e.g., public health, social work, psychiatry), has been assembled to guide the research plan by incorporating input from multidimensional perspective. Trial registration: ClinicalTrials.gov: NCT02543359
date: 2015-09-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29143/1/art%253A10.1186%252Fs13012-015-0324-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29143/7/licence.txt
identifier:   Herschell, AD and Kolko, DJ and Scudder, AT and Taber-Thomas, S and Schaffner, KF and Hiegel, SA and Iyengar, S and Chaffin, M and Mrozowski, S  (2015) Protocol for a statewide randomized controlled trial to compare three training models for implementing an evidence-based treatment.  Implementation Science, 10 (1).       
relation: 10.1186/s13012-015-0324-z

relation: http://d-scholarship-dev.library.pitt.edu/29187/
title: Cognitive tasks during walking affect cerebral blood flow signal features in middle cerebral arteries and their correlation to gait characteristics
creator: Gatouillat, A
creator: Bleton, H
creator: VanSwearingen, J
creator: Perera, S
creator: Thompson, S
creator: Smith, T
creator: Sejdić, E
description: Gait is a complex process involving both cognitive and sensory ability and is strongly impacted by the environment. In this paper, we propose to study of the impact of a cognitive task during gait on the cerebral blood flow velocity, the blood flow signal features and the correlation of gait and blood flow features through a dual task methodology. Both cerebral blood flow velocity and gait characteristics of eleven participants with no history of brain or gait conditions were recorded using transcranial Doppler on mid-cerebral artery while on a treadmill. The cognitive task was induced by a backward counting starting from 10,000 with decrement of 7. Central blood flow velocity raw and envelope features were extracted in both time, frequency and time-scale domain; information-theoretic metrics were also extracted and statistical significances were inspected. A similar feature extraction was performed on the stride interval signal. Statistical differences between the cognitive and baseline trials, between the left and right mid-cerebral arteries signals and the impact of the antropometric variables where studied using linear mixed models. No statistical differences were found between the left and right mid-cerebral arteries flows or the baseline and cognitive state gait features, while statistical differences for specific features were measured between cognitive and baseline states. These statistical differences found between the baseline and cognitive states show that cognitive process has an impact on the cerebral activity during walking. The state was found to have an impact on the correlation between the gait and blood flow features.
date: 2015-09-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29187/1/art%253A10.1186%252Fs12993-015-0073-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29187/7/licence.txt
identifier:   Gatouillat, A and Bleton, H and VanSwearingen, J and Perera, S and Thompson, S and Smith, T and Sejdić, E  (2015) Cognitive tasks during walking affect cerebral blood flow signal features in middle cerebral arteries and their correlation to gait characteristics.  Behavioral and Brain Functions, 11 (1).       
relation: 10.1186/s12993-015-0073-9

relation: http://d-scholarship-dev.library.pitt.edu/28381/
title: A pilot study of demographic and dopaminergic genetic contributions to weight change in kidney transplant recipients
creator: Stanfill, A
creator: Hathaway, D
creator: Cashion, A
creator: Homayouni, R
creator: Cowan, P
creator: Thompson, C
creator: Madahian, B
creator: Conley, Y
description: Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.
date: 2015-09-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28381/1/journal.pone.0138885.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28381/3/licence.txt
identifier:   Stanfill, A and Hathaway, D and Cashion, A and Homayouni, R and Cowan, P and Thompson, C and Madahian, B and Conley, Y  (2015) A pilot study of demographic and dopaminergic genetic contributions to weight change in kidney transplant recipients.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0138885

relation: http://d-scholarship-dev.library.pitt.edu/29193/
title: Relationship between fibroblastic foci profusion and high resolution CT morphology in fibrotic lung disease
creator: Walsh, SLF
creator: Wells, AU
creator: Sverzellati, N
creator: Devaraj, A
creator: von der Thüsen, J
creator: Yousem, SA
creator: Colby, TV
creator: Nicholson, AG
creator: Hansell, DM
description: Background: Fibroblastic foci profusion on histopathology and severity of traction bronchiectasis on highresolution computed tomography (HRCT) have been shown to be predictors of mortality in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the relationship between fibroblastic foci (FF) profusion and HRCT patterns in patients with a histopathologic diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (CHP). Methods: The HRCT scans of 162 patients with a histopathologic diagnosis of UIP or fibrotic NSIP (n = 162) were scored on extent of groundglass opacification, reticulation, honeycombing, emphysema and severity of traction bronchiectasis. For each patient, a fibroblastic foci profusion score based on histopathologic appearances was assigned. Relationships between extent of fibroblastic foci and individual HRCT patterns were investigated using univariate correlation analysis and multivariate linear regression. Results: Increasing extent of reticulation (P < 0.0001) and increasing severity of traction bronchiectasis (P < 0.0001) were independently associated with increasing FF score within the entire cohort. Within individual multidisciplinary team diagnosis subgroups, the only significant independent association with FF score was severity of traction bronchiectasis in patients with idiopathic pulmonary fibrosis (IPF)/UIP (n = 66, r2 = 0.19, P < 0.0001) and patients with chronic hypersensitivity pneumonitis (CHP) (n = 49, r2 = 0.45, P < 0.0001). Furthermore, FF score had the strongest association with severity of traction bronchiectasis in patients with IPF (r2 = 0.34, P < 0.0001) and CHP (r2 = 0.35, P < 0.0001). There was no correlation between FF score and severity of traction bronchiectasis in patients with fibrotic NSIP. Global disease extent had the strongest association with severity of traction bronchiectasis in patients with fibrotic NSIP (r2 = 0.58, P < 0.0001). Conclusion: In patients with fibrotic lung disease, profusion of fibroblastic foci is strikingly related to the severity of traction bronchiectasis, particularly in IPF and CHP. This may explain the growing evidence that traction bronchiectasis is a predictor of mortality in several fibrotic lung diseases.
date: 2015-09-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29193/1/art%253A10.1186%252Fs12916-015-0479-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29193/7/licence.txt
identifier:   Walsh, SLF and Wells, AU and Sverzellati, N and Devaraj, A and von der Thüsen, J and Yousem, SA and Colby, TV and Nicholson, AG and Hansell, DM  (2015) Relationship between fibroblastic foci profusion and high resolution CT morphology in fibrotic lung disease.  BMC Medicine, 13 (1).       
relation: 10.1186/s12916-015-0479-0

relation: http://d-scholarship-dev.library.pitt.edu/29195/
title: Is population structure sufficient to generate area-level inequalities in influenza rates? An examination using agent-based models
creator: Kumar, S
creator: Piper, K
creator: Galloway, DD
creator: Hadler, JL
creator: Grefenstette, JJ
description: Background: In New Haven County, CT (NHC), influenza hospitalization rates have been shown to increase with census tract poverty in multiple influenza seasons. Though multiple factors have been hypothesized to cause these inequalities, including population structure, differential vaccine uptake, and differential access to healthcare, the impact of each in generating observed inequalities remains unknown. We can design interventions targeting factors with the greatest explanatory power if we quantify the proportion of observed inequalities that hypothesized factors are able to generate. Here, we ask if population structure is sufficient to generate the observed area-level inequalities in NHC. To our knowledge, this is the first use of simulation models to examine the causes of differential poverty-related influenza rates. Methods: Using agent-based models with a census-informed, realistic representation of household size, age-structure, population density in NHC census tracts, and contact rates in workplaces, schools, households, and neighborhoods, we measured poverty-related differential influenza attack rates over the course of an epidemic with a 23 % overall clinical attack rate. We examined the role of asthma prevalence rates as well as individual contact rates and infection susceptibility in generating observed area-level influenza inequalities. Results: Simulated attack rates (AR) among adults increased with census tract poverty level (F = 30.5; P < 0.001) in an epidemic caused by a virus similar to A (H1N1) pdm09. We detected a steeper, earlier influenza rate increase in high-poverty census tracts - a finding that we corroborate with a temporal analysis of NHC surveillance data during the 2009 H1N1 pandemic. The ratio of the simulated adult AR in the highest- to lowest-poverty tracts was 33 % of the ratio observed in surveillance data. Increasing individual contact rates in the neighborhood did not increase simulated area-level inequalities. When we modified individual susceptibility such that it was inversely proportional to household income, inequalities in AR between high- and low-poverty census tracts were comparable to those observed in reality. Discussion: To our knowledge, this is the first study to use simulations to probe the causes of observed inequalities in influenza disease patterns. Knowledge of the causes and their relative explanatory power will allow us to design interventions that have the greatest impact on reducing inequalities. Conclusion: Differential exposure due to population structure in our realistic simulation model explains a third of the observed inequality. Differential susceptibility to disease due to prevailing chronic conditions, vaccine uptake, and smoking should be considered in future models in order to quantify the role of additional factors in generating influenza inequalities.
date: 2015-09-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29195/1/art%253A10.1186%252Fs12889-015-2284-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29195/7/licence.txt
identifier:   Kumar, S and Piper, K and Galloway, DD and Hadler, JL and Grefenstette, JJ  (2015) Is population structure sufficient to generate area-level inequalities in influenza rates? An examination using agent-based models.  BMC Public Health, 15 (1).       
relation: 10.1186/s12889-015-2284-2

relation: http://d-scholarship-dev.library.pitt.edu/28382/
title: Manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin reduces adiposity and improves insulin action in mice with pre-existing obesity
creator: Brestoff, JR
creator: Brodsky, T
creator: Sosinsky, AZ
creator: McLoughlin, R
creator: Stansky, E
creator: Fussell, L
creator: Sheppard, A
creator: DiSanto-Rose, M
creator: Kershaw, EE
creator: Reynolds, TH
description: The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression.
date: 2015-09-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28382/1/journal.pone.0137388.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28382/3/licence.txt
identifier:   Brestoff, JR and Brodsky, T and Sosinsky, AZ and McLoughlin, R and Stansky, E and Fussell, L and Sheppard, A and DiSanto-Rose, M and Kershaw, EE and Reynolds, TH  (2015) Manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin reduces adiposity and improves insulin action in mice with pre-existing obesity.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0137388

relation: http://d-scholarship-dev.library.pitt.edu/29196/
title: MEG-based neurofeedback for hand rehabilitation
creator: Foldes, ST
creator: Weber, DJ
creator: Collinger, JL
description: Background: Providing neurofeedback (NF) of motor-related brain activity in a biologically-relevant and intuitive way could maximize the utility of a brain-computer interface (BCI) for promoting therapeutic plasticity. We present a BCI capable of providing intuitive and direct control of a video-based grasp. Methods: Utilizing magnetoencephalography's (MEG) high temporal and spatial resolution, we recorded sensorimotor rhythms (SMR) that were modulated by grasp or rest intentions. SMR modulation controlled the grasp aperture of a stop motion video of a human hand. The displayed hand grasp position was driven incrementally towards a closed or opened state and subjects were required to hold the targeted position for a time that was adjusted to change the task difficulty. Results: We demonstrated that three individuals with complete hand paralysis due to spinal cord injury (SCI) were able to maintain brain-control of closing and opening a virtual hand with an average of 63 % success which was significantly above the average chance rate of 19 %. This level of performance was achieved without pre-training and less than 4 min of calibration. In addition, successful grasp targets were reached in 1.96 ± 0.15 s. Subjects performed 200 brain-controlled trials in approximately 30 min excluding breaks. Two of the three participants showed a significant improvement in SMR indicating that they had learned to change their brain activity within a single session of NF. Conclusions: This study demonstrated the utility of a MEG-based BCI system to provide realistic, efficient, and focused NF to individuals with paralysis with the goal of using NF to induce neuroplasticity.
date: 2015-09-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29196/1/art%253A10.1186%252Fs12984-015-0076-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29196/7/licence.txt
identifier:   Foldes, ST and Weber, DJ and Collinger, JL  (2015) MEG-based neurofeedback for hand rehabilitation.  Journal of NeuroEngineering and Rehabilitation, 12 (1).       
relation: 10.1186/s12984-015-0076-7

relation: http://d-scholarship-dev.library.pitt.edu/28383/
title: MicroRNA-10b is overexpressed and critical for cell survival and proliferation in medulloblastoma
creator: Pal, R
creator: Greene, S
description: This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNAarray, high expression of miRNA-10b inmedulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR). Two medulloblastoma cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10bmimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection ofmiRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, andmarkedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis ofmiRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5) and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanismwith Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival.
date: 2015-09-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28383/1/journal.pone.0137845.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28383/3/licence.txt
identifier:   Pal, R and Greene, S  (2015) MicroRNA-10b is overexpressed and critical for cell survival and proliferation in medulloblastoma.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0137845

relation: http://d-scholarship-dev.library.pitt.edu/26227/
title: Victims of Our Own Success: The Perils of <i>Obergefell</i> and <i>Windsor</i>
creator: Infanti, Anthony C
date: 2015-09-22
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26227/1/9_Infanti_-_FINAL.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26227/4/licence.txt
identifier:   Infanti, Anthony C  (2015) Victims of Our Own Success: The Perils of <i>Obergefell</i> and <i>Windsor</i>.  Ohio State Law Journal Furthermore, 76.  79 - 79.      

relation: http://d-scholarship-dev.library.pitt.edu/38904/
title: Experimental study and thermodynamic modeling of the Al–Co–Cr–Ni system
creator: Gheno, Thomas
creator: Liu, Xuan L
creator: Lindwall, Greta
creator: Liu, Zi-Kui
creator: Gleeson, Brian
description: A thermodynamic database for the Al–Co–Cr–Ni system is built via the Calphad method by extrapolating re-assessed ternary subsystems. A minimum number of quaternary parameters are included, which are optimized using experimental phase equilibrium data obtained by electron probe micro-analysis and x-ray diffraction analysis of NiCoCrAlY alloys spanning a wide compositional range, after annealing at 900 °C, 1100 °C and 1200 °C, and water quenching. These temperatures are relevant to oxidation and corrosion resistant MCrAlY coatings, where M corresponds to some combination of nickel and cobalt. Comparisons of calculated and measured phase compositions show excellent agreement for the β–γ equilibrium, and good agreement for three-phase β–γ–σ and β–γ–α equilibria. An extensive comparison with existing Ni-base databases (TCNI6, TTNI8, NIST) is presented in terms of phase compositions.
date: 2015-09-21
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/38904/2/Experimental%20study%20and%20thermodynamic%20modeling%20of%20the%20Al%20Co%20Cr%20Ni%20system.pdf
identifier:   Gheno, Thomas and Liu, Xuan L and Lindwall, Greta and Liu, Zi-Kui and Gleeson, Brian  (2015) Experimental study and thermodynamic modeling of the Al–Co–Cr–Ni system.  Science and Technology of Advanced Materials, 16 (5).  055001.  ISSN 1468-6996     
relation: https://www.tandfonline.com/doi/full/10.1088/1468-6996/16/5/055001
relation: 10.1088/1468-6996/16/5/055001

relation: http://d-scholarship-dev.library.pitt.edu/29197/
title: Biologic predictors of clinical improvement in rituximab-treated refractory myositis Clinical rheumatology and osteoporosis
creator: Reed, AM
creator: Crowson, CS
creator: Hein, M
creator: De Padilla, CL
creator: Olazagasti, JM
creator: Aggarwal, R
creator: Ascherman, DP
creator: Levesque, MC
creator: Oddis, CV
description: Background: To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab. Methods: In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n∈=∈177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n∈=∈28, TIF-γ n∈=∈19, Mi-2 n∈=∈25, SRP n∈=∈21, MJ n∈=∈18, non-MAA n∈=∈24, unidentified autoantibody n∈=∈9, and no autoantibodies n∈=∈33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons. Results: The mean (SD) values for muscle disease and physician global disease activity VAS scores (0-100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p∈<∈0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (- 6.7, - 6.1 and -7.2, p∈<∈.001). Both IFNCK high scores (>30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p∈=∈0.075). Conclusion: Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab.
date: 2015-09-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29197/1/art%253A10.1186%252Fs12891-015-0710-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29197/7/licence.txt
identifier:   Reed, AM and Crowson, CS and Hein, M and De Padilla, CL and Olazagasti, JM and Aggarwal, R and Ascherman, DP and Levesque, MC and Oddis, CV  (2015) Biologic predictors of clinical improvement in rituximab-treated refractory myositis Clinical rheumatology and osteoporosis.  BMC Musculoskeletal Disorders, 16 (1).       
relation: 10.1186/s12891-015-0710-3

relation: http://d-scholarship-dev.library.pitt.edu/28384/
title: Interdomain contacts and the stability of serralysin protease from Serratia marcescens
creator: Zhang, L
creator: Morrison, AJ
creator: Thibodeau, PH
description: The serralysin family of bacterial metalloproteases is associated with virulence in multiple modes of infection. These extracellular proteases are members of the Repeats-in-ToXin (RTX) family of toxins and virulence factors, which mediated virulence in E. coli, B. pertussis, and P. aeruginosa, as well as other animal and plant pathogens. The serralysin proteases are structurally dynamic and their folding is regulated by calcium binding to a Cterminal domain that defines the RTX family of proteins. Previous studies have suggested that interactions between N-terminal sequences and this C-terminal domain are important for the high thermal and chemical stabilities of the RTX proteases. Extending from this, stabilization of these interactions in the native structure may lead to hyperstabilization of the folded protein. To test this hypothesis, cysteine pairs were introduced into the N-terminal helix and the RTX domain and protease folding and activity were assessed. Under stringent pH and temperature conditions, the disulfide-bonded mutant showed increased protease activity and stability. This activity was dependent on the redox environment of the refolding reaction and could be blocked by selective modification of the cysteine residues before protease refolding. These data demonstrate that the thermal and chemical stability of these proteases is, in part, mediated by binding between the RTX domain and the N-terminal helix and demonstrate that stabilization of this interaction can further stabilize the active protease, leading to additional pH and thermal tolerance.
date: 2015-09-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28384/1/journal.pone.0138419.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28384/3/licence.txt
identifier:   Zhang, L and Morrison, AJ and Thibodeau, PH  (2015) Interdomain contacts and the stability of serralysin protease from Serratia marcescens.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0138419

relation: http://d-scholarship-dev.library.pitt.edu/28385/
title: The role of ARF6 in biliary atresia
creator: Ningappa, M
creator: So, J
creator: Glessner, J
creator: Ashokkumar, C
creator: Ranganathan, S
creator: Min, J
creator: Higgs, BW
creator: Sun, Q
creator: Haberman, K
creator: Schmitt, L
creator: Vilarinho, S
creator: Mistry, PK
creator: Vockley, G
creator: Dhawan, A
creator: Gittes, GK
creator: Hakonarson, H
creator: Jaffe, R
creator: Subramaniam, S
creator: Shin, D
creator: Sindhi, R
description: Background & Aims: Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA). Methods: To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6). Results: Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3' flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94 x 10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57 x 10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58 x 10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x 10-7), ERK/MAPK and CREB canonical pathways (p<1 x 10-34), and functional networks for cellular development and proliferation (p<1 x 10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA. Conclusions: The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also suggests a role for EGFR signaling in BA pathogenesis.
date: 2015-09-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28385/1/journal.pone.0138381.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28385/3/licence.txt
identifier:   Ningappa, M and So, J and Glessner, J and Ashokkumar, C and Ranganathan, S and Min, J and Higgs, BW and Sun, Q and Haberman, K and Schmitt, L and Vilarinho, S and Mistry, PK and Vockley, G and Dhawan, A and Gittes, GK and Hakonarson, H and Jaffe, R and Subramaniam, S and Shin, D and Sindhi, R  (2015) The role of ARF6 in biliary atresia.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0138381

relation: http://d-scholarship-dev.library.pitt.edu/29119/
title: It takes two to Tango: An exploration of domain pairs for cross-domain collaborative filtering
creator: Sahebi, S
creator: Brusilovsky, P
description: As the heterogeneity of data sources are increasing on the web, and due to the sparsity of data in each of these data sources, cross-domain recommendation is becoming an emerging research topic in the recent years. Cross-domain collaborative filtering aims to transfer the user rating pattern from source (auxiliary) domains to a target domain for the purpose of alleviating the sparsity problem and providing better target recommendations. However, the studies so far have either focused on a limited number of domains that are assumed to be related to each other (such as books and movies), or a division of the same dataset (such as movies) into different domains based on an item characteristic (such as genre). In this paper, we study a broad set of domains and their characteristics to understand the factors that affect the success or failure of cross-domain collaborative filtering, the amount of improvement in cross-domain approaches, and the selection of best source domains for a specific target domain. We propose to use Canonical Correlation Analysis (CCA) as a significant major factor in finding the most promising source domains for a target domain, and suggest a cross-domain collaborative filtering based on CCA (CDCCA) that proves to be successful in using the shared information between domains in the target recommendations.
date: 2015-09-16
type: Article
type: PeerReviewed
format: application/zip
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29119/4/10.1145/2810000/2800188/supp/rec180.zip_ip%3D136.142.171.21%26id%3D2800188%26acc%3DACTIVE%20SERVICE%26key%3DAA86BE8B6928DDC7.3F18A282B75518AA.4D4702B0C3E38B35.4D4702B0C3E38B35%26CFID%3D651976367%26CFTOKEN%3D85380483%26__acm__%3D1470329400_b6e3efbc5c367359fd023ebfe5fcad35
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29119/5/licence.txt
identifier:   Sahebi, S and Brusilovsky, P  (2015) It takes two to Tango: An exploration of domain pairs for cross-domain collaborative filtering.  RecSys 2015 - Proceedings of the 9th ACM Conference on Recommender Systems.  131 - 138.      
relation: 10.1145/2792838.2800188

relation: http://d-scholarship-dev.library.pitt.edu/29200/
title: Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma
creator: Tarhini, AA
creator: Zahoor, H
creator: Lin, Y
creator: Malhotra, U
creator: Sander, C
creator: Butterfield, LH
creator: Kirkwood, JM
description: Background: We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome. Methods: Patients were treated with ipilimumab (10mg/kg IV every 3weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab). Based on our prior data, the association of IL-17 and immune related colitis was tested. Serum cytokines were divided into functional groups (Th1, Th2, Regulatory, Proinflammatory) and were assessed at baseline and week 6 using sparse-group Lasso modeling to assess the association of various cytokine groups with progression free survival (PFS). The linear combination of the cytokines/chemokines in this model was then used as a risk score and a Kaplan-Meier curve was generated to examine the association of the dichotomized score and PFS. Results: Thirty-five patients were enrolled whose staging was: IIIB (3; N2b), IIIC (30; N2c, N3), IV (2). Median follow-up was 18months. Among 33 evaluable patients, median PFS was 11months (95% CI=6.2-19.2). IL-17 was found to correlate significantly with the incidence of grade 3 diarrhea/colitis when measured at baseline (p=0.02) with a trend towards significance at 6weeks (p=0.06). In the modeling analysis, at baseline, the linear combination of 2 regulatory cytokines [TGF- β1 (p=0.19) and IL-10 (p=-0.34)] was significantly associated with PFS (HR 2.66; p=0.035). No significant correlations with clinical outcomes were found in examining the week 6 cytokines. Conclusions: Baseline IL-17 level was significantly associated with the later development of severe diarrhea/colitis while the combination of baseline TGF- β1 and IL-10 levels were associated with therapeutic clinical outcome after neoadjuvant ipilimumab. These findings warrant further investigation and validation. Trial registration: ClinicalTrials.gov Identifier NCT00972933.
date: 2015-09-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29200/1/art%253A10.1186%252Fs40425-015-0081-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29200/7/licence.txt
identifier:   Tarhini, AA and Zahoor, H and Lin, Y and Malhotra, U and Sander, C and Butterfield, LH and Kirkwood, JM  (2015) Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma.  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0081-1

relation: http://d-scholarship-dev.library.pitt.edu/28386/
title: Inhaled carbon monoxide protects against the development of shock and mitochondrial injury following hemorrhage and resuscitation
creator: Gomez, H
creator: Kautza, B
creator: Escobar, D
creator: Nassour, I
creator: Luciano, J
creator: Botero, AM
creator: Gordon, L
creator: Martinez, S
creator: Holder, A
creator: Ogundele, O
creator: Loughran, P
creator: Rosengart, MR
creator: Pinsky, M
creator: Shiva, S
creator: Zuckerbraun, BS
description: Aims: Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. Results: Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). Conclusion: These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.
date: 2015-09-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28386/1/journal.pone.0135032.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28386/3/licence.txt
identifier:   Gomez, H and Kautza, B and Escobar, D and Nassour, I and Luciano, J and Botero, AM and Gordon, L and Martinez, S and Holder, A and Ogundele, O and Loughran, P and Rosengart, MR and Pinsky, M and Shiva, S and Zuckerbraun, BS  (2015) Inhaled carbon monoxide protects against the development of shock and mitochondrial injury following hemorrhage and resuscitation.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0135032

relation: http://d-scholarship-dev.library.pitt.edu/29202/
title: Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome
creator: Shaw, AD
creator: Schermer, CR
creator: Lobo, DN
creator: Munson, SH
creator: Khangulov, V
creator: Hayashida, DK
creator: Kellum, JA
description: Introduction: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. Methods: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98 %) received 0.9 % saline whereas 1706 (2 %) received a calcium-free balanced solution as the primary fluid. Results: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27 % vs. 1.03 %, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P <0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P <0.001). No differences were found in acute renal failure. Conclusions: In this large electronic health record, the predominant use of 0.9 % saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. Trial registration:NCT02083198clinicaltrials.gov; March 5, 2014
date: 2015-09-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29202/1/art%253A10.1186%252Fs13054-015-1045-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29202/7/licence.txt
identifier:   Shaw, AD and Schermer, CR and Lobo, DN and Munson, SH and Khangulov, V and Hayashida, DK and Kellum, JA  (2015) Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-1045-z

relation: http://d-scholarship-dev.library.pitt.edu/26384/
title: ptp++: A Precision Time Protocol Simulation Model for OMNeT++/INET
creator: Levesque, Martin
creator: Tipper, David
description: Precise time synchronization is expected to play a key role in emerging distributed and real-time applications such as the smart grid and Internet of Things (IoT) based applications. The Precision Time Protocol (PTP) is currently viewed as one of the main synchronization solutions over a packet-switched network, which supports microsecond synchronization accuracy. In this paper, we present a PTP simulation model for OMNeT++ INET, which allows to investigate the synchronization accuracy under different network configurations and conditions. To show some illustrative simulation results using the developed module, we investigate on the network load fluctuations and their impacts on the PTP performance by considering a network with class- based quality-of-service (QoS) support. The simulation results show that the network load significantly affects the network delay symmetry, and investigate a new technique called class probing to improve the PTP accuracy and mitigate the load fluctuation effects.
publisher: arXiv.org
date: 2015-09-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26384/1/1509.03169v1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26384/4/licence.txt
identifier:   Levesque, Martin and Tipper, David  (2015) ptp++: A Precision Time Protocol Simulation Model for OMNeT++/INET.  Proceedings of OMNeT++ Community Summit 2015.       
relation: http://arxiv.org/abs/1509.03169

relation: http://d-scholarship-dev.library.pitt.edu/28391/
title: An unusual phage repressor encoded by mycobacteriophage BPs
creator: Villanueva, VM
creator: Oldfield, LM
creator: Hatfull, GF
description: Temperate bacteriophages express transcription repressors that maintain lysogeny by down-regulating lytic promoters and confer superinfection immunity. Repressor regulation is critical to the outcome of infection - lysogenic or lytic growth - as well as prophage induction into lytic replication. Mycobacteriophage BPs and its relatives use an unusual integration- dependent immunity system in which the phage attachment site (attP) is located within the repressor gene (33) such that site-specific integration leads to synthesis of a prophageencoded product (gp33103) that is 33 residues shorter at its C-terminus than the virallyencoded protein (gp33136). However, the shorter form of the repressor (gp33103) is stable and active in repression of the early lytic promoter PR, whereas the longer virally-encoded form (gp33136) is inactive due to targeted degradation via a C-terminal ssrA-like tag. We show here that both forms of the repressor bind similarly to the 33-34 intergenic regulatory region, and that BPs gp33103 is a tetramer in solution. The BPs gp33103 repressor binds to five regulatory regions spanning the BPs genome, and regulates four promoters including the early lytic promoter, PR. BPs gp33103 has a complex pattern of DNA recognition in which a full operator binding site contains two half sites separated by a variable spacer, and BPs gp33103 induces a DNA bend at the full operator site but not a half site. The operator site structure is unusual in that one half site corresponds to a 12 bp palindrome identified previously, but the other half site is a highly variable variant of the palindrome. Copyright:
date: 2015-09-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28391/1/journal.pone.0137187_%281%29.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28391/3/licence.txt
identifier:   Villanueva, VM and Oldfield, LM and Hatfull, GF  (2015) An unusual phage repressor encoded by mycobacteriophage BPs.  PLoS ONE, 10 (9).       
relation: 10.1371/journal.pone.0137187

relation: http://d-scholarship-dev.library.pitt.edu/26288/
title: LOL in the age of the telegraph
creator: Collister, Lauren Brittany
description: From “lol” to “brb,” the internet and text messaging gave rise to a unique form of short form language – “textspeak” – in which almost all of us are well-versed. But long before the internet revolutionized communication, humans experienced a different sort of technological innovation: the telegraph. In 1837, the first commercial telegraphs were released by Samuel Morse, William Fothergill Cooke and Charles Wheatstone, and this machine – as journalist Tom Standage argues in his book The Victorian Internet – mirrored the impact that the internet has had in modern times. The result was an entirely new way to wield language – one that, in a number of ways, resembles today’s textspeak.
date: 2015-09-01
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26288/1/licence.txt
identifier:   Collister, Lauren Brittany  (2015) LOL in the age of the telegraph.  The Conversation.       
relation: https://theconversation.com/lol-in-the-age-of-the-telegraph-42578

relation: http://d-scholarship-dev.library.pitt.edu/26784/
title: The Pennsylvania historical and museum commission and the papers of the harmony society: An acquisition, a five-decade loan, and recovery
creator: Mattern, E
description: Among archivists and manuscript collectors, the term "replevin" commonly describes efforts by government archives to recover public records that are in private hands. At times, such efforts can provoke friction, raising questions about the line between public and private property rights. This article chronicles an atypical replevin case in Pennsylvania, one that focuses on the struggles over the ownership of papers of a private origin, but which became government property with their transfer to the Commonwealth in 1937. This is a custodial history of a collection of papers documenting the Harmony Society, a religious separatist society once located in western Pennsylvania and in southwest Indiana. It is a story that involves a former Harmonist, a scholar, misplaced trust, and recovery that highlights the complex psychology of ownership.
date: 2015-09-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26784/1/Mattern_FinalPrePrint.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26784/4/licence.txt
identifier:   Mattern, E  (2015) The Pennsylvania historical and museum commission and the papers of the harmony society: An acquisition, a five-decade loan, and recovery.  Pennsylvania History, 82 (4).  516 - 535.  ISSN 0031-4528     
relation: 10.5325/pennhistory.82.4.0516

relation: http://d-scholarship-dev.library.pitt.edu/25510/
title: A Secure Communication Architecture for Distributed Microgrid Control
creator: Kounev, V
creator: Tipper, D
creator: Yavuz, AA
creator: Grainger, BM
creator: Reed, GF
description: Microgrids are a key component in the evolution of the power grid. Microgrids are required to operate in both grid connected and standalone island mode using local sources of power. A major challenge in implementing microgrids is the communications and control to support transition from grid connected mode and operation in island mode. Here, we propose a secure communication architecture to support microgrid operation and control. A security model, including network, data, and attack models, is defined and a security protocol to address the real-time communication needs of microgrids is proposed. The implementation of the proposed security scheme is discussed and its performance evaluated using theoretical and co-simulation analysis, which shows it to be superior to existing protocols.
date: 2015-09-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25510/1/licence.txt
identifier:   Kounev, V and Tipper, D and Yavuz, AA and Grainger, BM and Reed, GF  (2015) A Secure Communication Architecture for Distributed Microgrid Control.  IEEE Transactions on Smart Grid, 6 (5).  2484 - 2492.  ISSN 1949-3053     
relation: 10.1109/TSG.2015.2424160

relation: http://d-scholarship-dev.library.pitt.edu/25927/
title: The impact of image descriptions on user tagging behavior: A study of the nature and functionality of crowdsourced tags
creator: Lin, YL
creator: Trattner, C
creator: Brusilovsky, P
creator: He, D
description: Crowdsourcing has emerged as a way to harvest social wisdom from thousands of volunteers to perform a series of tasks online. However, little research has been devoted to exploring the impact of various factors such as the content of a resource or crowdsourcing interface design on user tagging behavior. Although images' titles and descriptions are frequently available in image digital libraries, it is not clear whether they should be displayed to crowdworkers engaged in tagging. This paper focuses on offering insight to the curators of digital image libraries who face this dilemma by examining (i) how descriptions influence the user in his/her tagging behavior and (ii) how this relates to the (a) nature of the tags, (b) the emergent folksonomy, and (c) the findability of the images in the tagging system. We compared two different methods for collecting image tags from Amazon's Mechanical Turk's crowdworkers - with and without image descriptions. Several properties of generated tags were examined from different perspectives: diversity, specificity, reusability, quality, similarity, descriptiveness, and so on. In addition, the study was carried out to examine the impact of image description on supporting users' information seeking with a tag cloud interface. The results showed that the properties of tags are affected by the crowdsourcing approach. Tags from the "with description" condition are more diverse and more specific than tags from the "without description" condition, while the latter has a higher tag reuse rate. A user study also revealed that different tag sets provided different support for search. Tags produced "with description" shortened the path to the target results, whereas tags produced without description increased user success in the search task.
date: 2015-09-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25927/1/CS-0131_chris_1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25927/4/licence.txt
identifier:   Lin, YL and Trattner, C and Brusilovsky, P and He, D  (2015) The impact of image descriptions on user tagging behavior: A study of the nature and functionality of crowdsourced tags.  Journal of the Association for Information Science and Technology, 66 (9).  1785 - 1798.  ISSN 2330-1635     
relation: 10.1002/asi.23292

relation: http://d-scholarship-dev.library.pitt.edu/26521/
title: Computer Access Technologies for Controlling Assistive Robotic Manipulators: Potentials and Challenges
creator: Ka, Hyun
creator: Ding, Dan
description: One of the most challenging barriers to a successful application of the assistive robots is how to enable users who have special needs to interact with the robot aids in an efficient and comfortable manner, since the conventional control method using a traditional joystick combined with buttons and/or knobs demands fine motor control and good dexterity resulting in cognitive and physical workload. Adopting computer access technology, which has provided an alternative means to allow people who have a wide range of special needs to independently access their computer, can be a practical solution to this issue. In this paper, we reviewed and discussed the potentials and challenges of computer access technologies as an alternative control method for controlling assistive robotic manipulators, focusing on most widely adopted interventions in the clinical settings, including alternative pointing, keyboard-only access, switch scanning interface and speech recognition.
publisher: Austin Publishing
date: 2015-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26521/1/Ka_AJRA.pdf
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26521/4/fulltext-ajra-v2-id1007.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26521/7/licence.txt
identifier:   Ka, Hyun and Ding, Dan  (2015) Computer Access Technologies for Controlling Assistive Robotic Manipulators: Potentials and Challenges.  Journal of Robotics & Automation, 2 (1).       
relation: http://austinpublishinggroup.com/robotics-automation/download.php?file=fulltext/ajra-v2-id1007.pdf

relation: http://d-scholarship-dev.library.pitt.edu/29203/
title: Understanding and valuing the broader health system benefits of Uganda's national Human Resources for Health Information System investment
creator: Driessen, J
creator: Settle, D
creator: Potenziani, D
creator: Tulenko, K
creator: Kabocho, T
creator: Wadembere, I
description: Background: To address the need for timely and comprehensive human resources for health (HRH) information, governments and organizations have been actively investing in electronic health information interventions, including in low-resource settings. The economics of human resources information systems (HRISs) in low-resource settings are not well understood, however, and warrant investigation and validation. Case description: This case study describes Uganda's Human Resources for Health Information System (HRHIS), implemented with support from the US Agency for International Development, and documents perceptions of its impact on the health labour market against the backdrop of the costs of implementation. Through interviews with end users and implementers in six different settings, we document pre-implementation data challenges and consider how the HRHIS has been perceived to affect human resources decision-making and the healthcare employment environment. Discussion and evaluation: This multisite case study documented a range of perceived benefits of Uganda's HRHIS through interviews with end users that sought to capture the baseline (or pre-implementation) state of affairs, the perceived impact of the HRHIS and the monetary value associated with each benefit. In general, the system appears to be strengthening both demand for health workers (through improved awareness of staffing patterns) and supply (by improving licensing, recruitment and competency of the health workforce). This heightened ability to identify high-value employees makes the health sector more competitive for high-quality workers, and this elevation of the health workforce also has broader implications for health system performance and population health. Conclusions: Overall, it is clear that HRHIS end users in Uganda perceived the system to have significantly improved day-to-day operations as well as longer term institutional mandates. A more efficient and responsive approach to HRH allows the health sector to recruit the best candidates, train employees in needed skills and deploy trained personnel to facilities where there is real demand. This cascade of benefits can extend the impact and rewards of working in the health sector, which elevates the health system as a whole.
date: 2015-08-31
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29203/1/art%253A10.1186%252Fs12960-015-0036-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29203/7/licence.txt
identifier:   Driessen, J and Settle, D and Potenziani, D and Tulenko, K and Kabocho, T and Wadembere, I  (2015) Understanding and valuing the broader health system benefits of Uganda's national Human Resources for Health Information System investment.  Human Resources for Health, 13 (1).       
relation: 10.1186/s12960-015-0036-0

relation: http://d-scholarship-dev.library.pitt.edu/29204/
title: Exogenous activated NK cells enhance trafficking of endogenous NK cells to endometriotic lesions
creator: Montenegro, ML
creator: Ferriani, RA
creator: Basse, PH
description: Background: Endometriosis is defined as the presence of endometrial glands and stroma at ectopic locations. Although the prevalence of endometriosis is as high as 35 %-50 %, its pathogenesis remains controversial. An increasing number of studies suggest that changes in immune reactivity may be primarily involved in the development of endometriosis development. In this sense, it has been strongly suggested that a fundamental part of immunologic system, the natural killer cells (NK cells), are an important part of this process. NK cells, a component of the innate immune system, have been extensively studied for their ability to defend the organism against infections and malignancy. Recent studies have shown that IL-2-activated NK (A-NK) cells are able to attack and destroy tumors in lungs and livers of mice, demonstrating the therapeutic potential of these cells. Similarly to metastatic tumor cells, endometrial cells are able to adhere, infiltrate and proliferate at ectopic locations. Therefore, in this study, we evaluated the ability of adoptively transferred and endogenous NK cells to infiltrate endometriosis lesions. Methods: As NK cells donors were used C57BL/6 B6. PL- Thy 1.1 female mice. As uterine horns donors were used C57/BL6+GFP female mice and as endometriosis recipients C57BL/6 Thy1.2 female mice. Endometriosis induction was made by injection of endometrial tissue fragments. After 4 weeks, necessary for endometriosis lesions establishment the animals were divided in 3 experimental groups with 10 animals each. Group 1 received i.v doses of 5x106 A-NK in 200μl RPMI; Group 2 received i.p dose of 5x106 A-NK in 200μl RPMI and Group 3 received i.p dose of IL2 (0.5 mL RPMI containing 5.000U of IL2). Results: Our data show that exogenous A-NK cells injected via ip combined with endogenous A-NK cells seems to be the most efficient way for activated NK cells track and infiltrate endometriosis. Conclusion: For the first time, it was shown that both endogenous as exogenous A-NK cells are able to track, migrate and infiltrate endometriosis lesion. This seems to be a promising result, and if confirmed the efficiency of A-NK cells in killing endometriosis lesions, maybe in the future we could use this approach as an alternative treatment for women with endometriosis.
date: 2015-08-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29204/1/art%253A10.1186%252Fs12865-015-0105-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29204/7/licence.txt
identifier:   Montenegro, ML and Ferriani, RA and Basse, PH  (2015) Exogenous activated NK cells enhance trafficking of endogenous NK cells to endometriotic lesions.  BMC Immunology, 16 (1).       
relation: 10.1186/s12865-015-0105-0

relation: http://d-scholarship-dev.library.pitt.edu/28393/
title: C/EBPβ promotes immunity to oral candidiasis through regulation of β-defensins
creator: Simpson-Abelson, MR
creator: Childs, EE
creator: Ferreira, MC
creator: Bishu, S
creator: Conti, HR
creator: Gaffen, SL
description: Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream events that control immunity to this fungus are poorly understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBPβ is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBPβ in vivo is poorly understood, in part because C/EBPβ-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBPβ in the context of an IL-17-dependent immune response, using C. albicans infection as a model system. Confirming prior findings, we found that C/EBPβ is required for immunity to systemic candidiasis. In contrast, C/EBPβ-/- mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBPβ-/- mice experienced more severe OPC than WT mice in the context of cortisoneinduced immunosuppression. Expression of the antimicrobial peptide β-defensin (BD)-3 correlated strongly with susceptibility in C/EBPβ-/- mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBPβ contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to β-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response. Copyright:
date: 2015-08-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28393/1/journal.pone.0136538.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28393/3/licence.txt
identifier:   Simpson-Abelson, MR and Childs, EE and Ferreira, MC and Bishu, S and Conti, HR and Gaffen, SL  (2015) C/EBPβ promotes immunity to oral candidiasis through regulation of β-defensins.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0136538

relation: http://d-scholarship-dev.library.pitt.edu/28392/
title: DNA-launched alphavirus replicons encoding a fusion of mycobacterial antigens Acr and Ag85B are immunogenic and protective in a murine model of TB infection
creator: Dalmia, N
creator: Klimstra, WB
creator: Mason, C
creator: Ramsay, AJ
description: There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr) and antigen 85B (Ag85B), termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNAlaunched Vrep may, therefore, represent an effective approach to the development of genebased vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters.
date: 2015-08-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28392/1/journal.pone.0136635.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28392/3/licence.txt
identifier:   Dalmia, N and Klimstra, WB and Mason, C and Ramsay, AJ  (2015) DNA-launched alphavirus replicons encoding a fusion of mycobacterial antigens Acr and Ag85B are immunogenic and protective in a murine model of TB infection.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0136635

relation: http://d-scholarship-dev.library.pitt.edu/29208/
title: Hydroxyurea therapy for children with sickle cell disease: Describing how caregivers make this decision
creator: Creary, S
creator: Zickmund, S
creator: Ross, D
creator: Krishnamurti, L
creator: Bogen, DL
description: Background: Hydroxyurea (HU) is underutilized in children with sickle cell disease (SCD) because caregivers frequently decline HU when it is offered. This study explores what impacts this decision. Results: Caregivers of children with clinically severe SCD whose children were offered HU previously were interviewed. We used a qualitative analytical approach to analyze their telephone interview transcripts. Caregivers who chose HU (n = 9) reported their children had severe SCD, sought detailed information about HU, and accepted HU as a preventative therapy. In contrast, caregivers who did not choose HU (n = 10) did not perceive their children as having severe SCD and did not question their child's provider about HU. Conclusions: This study identifies specific areas that providers should address to when they discuss HU with families so that they can make informed decisions. Our study also uncovered factors that are important to consider when designing future interventions to improve hydroxyurea acceptance and when developing decision-aid tools to assist caregivers of children with SCD who are considering disease modifying therapies.
date: 2015-08-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29208/1/art%253A10.1186%252Fs13104-015-1344-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29208/7/licence.txt
identifier:   Creary, S and Zickmund, S and Ross, D and Krishnamurti, L and Bogen, DL  (2015) Hydroxyurea therapy for children with sickle cell disease: Describing how caregivers make this decision.  BMC Research Notes, 8 (1).       
relation: 10.1186/s13104-015-1344-0

relation: http://d-scholarship-dev.library.pitt.edu/29209/
title: Liver trauma: WSES position paper
creator: Coccolini, F
creator: Montori, G
creator: Catena, F
creator: Di Saverio, S
creator: Biffl, W
creator: Moore, EE
creator: Peitzman, AB
creator: Rizoli, S
creator: Tugnoli, G
creator: Sartelli, M
creator: Manfredi, R
creator: Ansaloni, L
description: The liver is the most injured organ in abdominal trauma. Road traffic crashes and antisocial, violent behavior account for the majority of liver injuries. The present position paper represents the position of the World Society of Emergency Surgery (WSES) about the management of liver injuries.
date: 2015-08-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29209/1/art%253A10.1186%252Fs13017-015-0030-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29209/7/licence.txt
identifier:   Coccolini, F and Montori, G and Catena, F and Di Saverio, S and Biffl, W and Moore, EE and Peitzman, AB and Rizoli, S and Tugnoli, G and Sartelli, M and Manfredi, R and Ansaloni, L  (2015) Liver trauma: WSES position paper.  World Journal of Emergency Surgery, 10 (1).       
relation: 10.1186/s13017-015-0030-9

relation: http://d-scholarship-dev.library.pitt.edu/28396/
title: Genomic copy number variations in the genomes of leukocytes predict prostate cancer clinical outcomes
creator: Yu, YP
creator: Liu, S
creator: Huo, Z
creator: Martin, A
creator: Nelson, JB
creator: Tseng, GC
creator: Luo, JH
description: Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV) were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness. A prostate cancer outcome prediction model was developed based on large size ratio of CNV from the leukocyte genomes. This prediction model generated an average prediction rate of 75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer recurrence. When combined with Nomogram and the status of fusion transcripts, the average prediction rate was improved to 82.5%with sensitivity of 84.8%and specificity of 78.2%. In addition, the leukocyte prediction model was 62.6%accurate in predicting short prostate specific antigen doubling time. When combined with Gleason's grade, Nomogram and the status of fusion transcripts, the prediction model generated a correct prediction rate of 77.5% with 73.7% sensitivity and 80.1% specificity. To our knowledge, this is the first study showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a human malignancy. Copyright:
date: 2015-08-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28396/1/journal.pone.0135982.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28396/3/licence.txt
identifier:   Yu, YP and Liu, S and Huo, Z and Martin, A and Nelson, JB and Tseng, GC and Luo, JH  (2015) Genomic copy number variations in the genomes of leukocytes predict prostate cancer clinical outcomes.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0135982

relation: http://d-scholarship-dev.library.pitt.edu/28395/
title: Statistical machines for trauma hospital outcomes research: Application to the PRospective, Observational, Multi-center Major trauma Transfusion (PROMMTT) study
creator: Moore, SE
creator: Decker, A
creator: Hubbard, A
creator: Callcut, RA
creator: Fox, EE
creator: Del Junco, DJ
creator: Holcomb, JB
creator: Rahbar, MH
creator: Wade, CE
creator: Schreiber, MA
creator: Alarcon, LH
creator: Brasel, KJ
creator: Bulger, EM
creator: Cotton, BA
creator: Muskat, P
creator: Myers, JG
creator: Phelan, HA
creator: Cohen, MJ
description: Improving the treatment of trauma, a leading cause of death worldwide, is of great clinical and public health interest. This analysis introduces flexible statistical methods for estimating center-level effects on individual outcomes in the context of highly variable patient populations, such as those of the PRospective, Observational, Multi-center Major Trauma Transfusion study. Ten US level I trauma centers enrolled a total of 1,245 trauma patients who survived at least 30 minutes after admission and received at least one unit of red blood cells. Outcomes included death, multiple organ failure, substantial bleeding, and transfusion of blood products. The centers involved were classified as either large or small-volume based on the number of massive transfusion patients enrolled during the study period. We focused on estimation of parameters inspired by causal inference, specifically estimated impacts on patient outcomes related to the volume of the trauma hospital that treated them. We defined this association as the change in mean outcomes of interest that would be observed if, contrary to fact, subjects from large-volume sites were treated at small-volume sites (the effect of treatment among the treated). We estimated this parameter using three different methods, some of which use data-adaptive machine learning tools to derive the outcome models, minimizing residual confounding by reducing model misspecification. Differences between unadjusted and adjusted estimators sometimes differed dramatically, demonstrating the need to account for differences in patient characteristics in clinic comparisons. In addition, the estimators based on robust adjustment methods showed potential impacts of hospital volume. For instance, we estimated a survival benefit for patients who were treated at large-volume sites, which was not apparent in simpler, unadjusted comparisons. By removing arbitrary modeling decisions from the estimation process and concentrating on parameters that have more direct policy implications, these potentially automated approaches allow methodological standardization across similar comparativeness effectiveness studies.
date: 2015-08-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28395/1/journal.pone.0136438.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28395/3/licence.txt
identifier:   Moore, SE and Decker, A and Hubbard, A and Callcut, RA and Fox, EE and Del Junco, DJ and Holcomb, JB and Rahbar, MH and Wade, CE and Schreiber, MA and Alarcon, LH and Brasel, KJ and Bulger, EM and Cotton, BA and Muskat, P and Myers, JG and Phelan, HA and Cohen, MJ  (2015) Statistical machines for trauma hospital outcomes research: Application to the PRospective, Observational, Multi-center Major trauma Transfusion (PROMMTT) study.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0136438

relation: http://d-scholarship-dev.library.pitt.edu/28394/
title: A refined neuronal population measure of visual attention
creator: Mayo, JP
creator: Cohen, MR
creator: Maunsell, JHR
description: Neurophysiological studies of cognitive mechanisms such as visual attention typically ignore trial-by-trial variability and instead report mean differences averaged across many trials. Advances in electrophysiology allow for the simultaneous recording of small populations of neurons, which may obviate the need for averaging activity over trials. We recently introduced a method called the attention axis that uses multi-electrode recordings to provide estimates of attentional state of behaving monkeys on individual trials. Here, we refine this method to eliminate problems that can cause bias in estimates of attentional state in certain scenarios. We demonstrate the sources of these problems using simulations and propose an amendment to the previous formulation that provides superior performance in trial-bytrial assessments of attentional state. Copyright:
date: 2015-08-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28394/1/journal.pone.0136570.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28394/3/licence.txt
identifier:   Mayo, JP and Cohen, MR and Maunsell, JHR  (2015) A refined neuronal population measure of visual attention.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0136570

relation: http://d-scholarship-dev.library.pitt.edu/37613/
title: Evaluation of left ventricular strain in patients with type-2 diabetes mellitus using three-dimensional speckle tracking
creator: Rui, YF
creator: Yan, ZN
creator: Fan, L
creator: Feng, YP
description: Objective: To evaluate left ventricular strain in patients with type-2 diabetes mellitus (2-DM) using three-dimensional speckle tracking imaging (3D-STI). Methods: Thirty patients with 2-DM (DM group) and 30 healthy volunteers (control group) underwent 3D-STI. The globe and segments of strain left ventricular were compared between groups. Results: The global strain (GS), global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS) in DM group were decreased than thoses in control group (t=2.18, 3.27, 2.05, 3.76, all P<0.05). The systolic peak circumferential strains of left ventricular anterior and lateral walls in 2-DM group were decreased than those in control group (both P<0.05). The systolic peak radial strains of lateral wall, basal and middle anterior walls in 2-DM group were decreased than those in control group (all P<0.05). The systolic peak longitudinal strains of basal anterior septum, basal and middle anterior walls, middle and apical lateral walls, apical inferior wall in 2-DM group were decreased than those in control group (all P<0.05). In DM group, the systolic peak radial and longitudinal strains of basal segment were decreased than those of apical segment, and the longitudinal strain of middle segment was decreased than that of apical segment (all P<0.05). In control group, the systolic peak circumferential, radial and longitudinal strains of basal segment were decreased than those of apical segment, and the longitudinal strain of middle segment were decreased than that of apical segment (all P<0.05). Conclusion: 3D-ST is a useful technology not only in evaluating global function of left ventricular, but also in detecting early changes in segments.
date: 2015-08-20
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/37613/1/licenseagreement_dscholarship.txt
identifier:   Rui, YF and Yan, ZN and Fan, L and Feng, YP  (2015) Evaluation of left ventricular strain in patients with type-2 diabetes mellitus using three-dimensional speckle tracking.  Chinese Journal of Medical Imaging Technology, 31 (8).  1207 - 1211.  ISSN 1003-3289     
relation: 10.13929/j.1003-3289.2015.08.022

relation: http://d-scholarship-dev.library.pitt.edu/29210/
title: Combination immunotherapy: Where do we go from here?
creator: Overacre, AE
creator: Kurtulus, S
creator: Sznol, M
creator: Pardoll, DM
creator: Anderson, A
creator: Vignali, DAA
description: The remarkable clinical success of cancer immunotherapies targeting the checkpoint receptors CTLA-4 and PD-1 has generated considerable excitement and emboldened efforts to build on this important foundation. Research efforts are now focused on understanding the mechanism of action of these immunotherapies, identifying new inhibitory mechanisms that could be targeted to achieve responses in patients with refractory cancers, and developing approaches that might exhibit efficacy against "immunologically inert" tumors. The outstanding challenges in moving forward are developing reliable strategies for determining which patients will respond optimally to a given immunotherapy, and what combination of immunotherapies and conventional therapies will prove beneficial against each tumor type. These issues were discussed in a one-day workshop at the SITC meeting in November 2014.
date: 2015-08-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29210/1/art%253A10.1186%252Fs40425-015-0083-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29210/7/licence.txt
identifier:   Overacre, AE and Kurtulus, S and Sznol, M and Pardoll, DM and Anderson, A and Vignali, DAA  (2015) Combination immunotherapy: Where do we go from here?  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0083-z

relation: http://d-scholarship-dev.library.pitt.edu/38903/
title: Projection Stereolithographic Fabrication of Human Adipose Stem Cell-Incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering
creator: Sun, Aaron X.
creator: Lin, Hang
creator: Beck, Angela M.
creator: Kilroy, Evan J.
creator: Tuan, Rocky S.
description: Poor self-healing ability of cartilage necessitates the development of methods for cartilage regeneration. Scaffold construction with live stem cell incorporation and subsequent differentiation presents a promising route. Projection stereolithography (PSL) offers high resolution and processing speed as well as the ability to fabricate scaffolds that precisely fit the anatomy of cartilage defects using medical imaging as the design template. We report here the use of a visible-light based PSL (VL-PSL) system to encapsulate human adipose-derived stem cells (hASCs) into a biodegradable polymer (poly-D,L-lactic acid/polyethylene glycol/ poly-D,L-lactic acid (PDLLA-PEG))/hyaluronic acid (HA) matrix to produce live cell constructs with customized architectures. After fabrication, hASCs showed high viability (84%) and were uniformly distributed throughout the constructs, which possessed high mechanical property with a compressive modulus of 780 kPa. The hASC-seeded constructs were then cultured in Control or TGF-β3-containing chondrogenic medium for up to 28 days. In chondrogenic medium treated group (TGF-β3 group) hASCs maintained 77% viability and expressed chondrogenic genes Sox9, collagen type II, and aggrecan at 11, 232, and 2.29 x 10(5) fold increases, respectively, compared to levels at day 0 in non-chondrogenic medium. The TGF-β3 group also produced a collagen type II and glycosaminoglycan (GAG)-rich extracellular matrix, detected by immunohistochemistry, and Alcian blue and Safranin O staining suggesting robust chondrogenesis within the scaffold. Without chondroinductive addition (Control group), cell viability decreased with time (65% at 28 days) and showed poor cartilage matrix deposition. After 28 days, mechanical strength of the TGF-β3 group remained high at 240 kPa. Thus, the PSL- and PLLA-PEG/HA based fabrication method using adult stem cells is a promising approach in producing mechanically competent engineered cartilage for joint cartilage resurfacing.
publisher: Frontiers Media S.A.
date: 2015-08-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/38903/2/fbioe-03-00115.pdf
identifier:   Sun, Aaron X. and Lin, Hang and Beck, Angela M. and Kilroy, Evan J. and Tuan, Rocky S.  (2015) Projection Stereolithographic Fabrication of Human Adipose Stem Cell-Incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering.  Frontiers in Bioengineering and Biotechnology, 3.   ISSN 2296-4185     
relation: https://www.frontiersin.org/articles/10.3389/fbioe.2015.00115/full
relation: 10.3389/fbioe.2015.00115

relation: http://d-scholarship-dev.library.pitt.edu/29212/
title: cMRI-BED: A novel informatics framework for cardiac MRI biomarker extraction and discovery applied to pediatric cardiomyopathy classification
creator: Gopalakrishnan, V
creator: Menon, PG
creator: Madan, S
description: Background: Pediatric cardiomyopathies are a rare, yet heterogeneous group of pathologies of the myocardium that are routinely examined clinically using Cardiovascular Magnetic Resonance Imaging (cMRI). This gold standard powerful non-invasive tool yields high resolution temporal images that characterize myocardial tissue. The complexities associated with the annotation of images and extraction of markers, necessitate the development of efficient workflows to acquire, manage and transform this data into actionable knowledge for patient care to reduce mortality and morbidity. Methods: We develop and test a novel informatics framework called cMRI-BED for biomarker extraction and discovery from such complex pediatric cMRI data that includes the use of a suite of tools for image processing, marker extraction and predictive modeling. We applied our workflow to obtain and analyze a dataset of 83 de-identified cases and controls containing cMRI-derived biomarkers for classifying positive versus negative findings of cardiomyopathy in children. Bayesian rule learning (BRL) methods were applied to derive understandable models in the form of propositional rules with posterior probabilities pertaining to their validity. Popular machine learning methods in the WEKA data mining toolkit were applied using default parameters to assess cross-validation performance of this dataset using accuracy and percentage area under ROC curve (AUC) measures. Results: The best 10-fold cross validation predictive performance obtained on this cMRI-derived biomarker dataset was 80.72% accuracy and 79.6% AUC by a BRL decision tree model, which is promising from this type of rare data. Moreover, we were able to verify that mycocardial delayed enhancement (MDE) status, which is known to be an important qualitative factor in the classification of cardiomyopathies, is picked up by our rule models as an important variable for prediction. Conclusions: Preliminary results show the feasibility of our framework for processing such data while also yielding actionable predictive classification rules that can augment knowledge conveyed in cardiac radiology outcome reports. Interactions between MDE status and other cMRI parameters that are depicted in our rules warrant further investigation and validation. Predictive rules learned from cMRI data to classify positive and negative findings of cardiomyopathy can enhance scientific understanding of the underlying interactions among imaging-derived parameters.
date: 2015-08-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29212/1/art%253A10.1186%252F1475-925X-14-S2-S7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29212/7/licence.txt
identifier:   Gopalakrishnan, V and Menon, PG and Madan, S  (2015) cMRI-BED: A novel informatics framework for cardiac MRI biomarker extraction and discovery applied to pediatric cardiomyopathy classification.  BioMedical Engineering Online, 14 (2).       
relation: 10.1186/1475-925X-14-S2-S7

relation: http://d-scholarship-dev.library.pitt.edu/28398/
title: Effects of a one year reusable contraceptive vaginal ring on vaginal Microflora and the risk of vaginal infection: An open-label prospective evaluation
creator: Huang, Y
creator: Merkatz, RB
creator: Hillier, SL
creator: Roberts, K
creator: Blithe, DL
creator: Sitruk-Ware, R
creator: Creinin, MD
description: Background A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1-year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora. Methods There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology substudy for up to 1-year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study. Results Over 1-year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H<inf>2</inf>O<inf>2</inf>-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7%at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 10<sup>7</sup> colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (10<sup>4</sup> to 10<sup>3</sup>cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed. Conclusion Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem.
date: 2015-08-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28398/1/journal.pone.0134460.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28398/3/licence.txt
identifier:   Huang, Y and Merkatz, RB and Hillier, SL and Roberts, K and Blithe, DL and Sitruk-Ware, R and Creinin, MD  (2015) Effects of a one year reusable contraceptive vaginal ring on vaginal Microflora and the risk of vaginal infection: An open-label prospective evaluation.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134460

relation: http://d-scholarship-dev.library.pitt.edu/28397/
title: Loss-of-function PTPRD mutations lead to increased STAT3 activation and sensitivity to STAT3 inhibition in head and neck cancer
creator: Peyser, ND
creator: Du, Y
creator: Li, H
creator: Lui, V
creator: Xiao, X
creator: Chan, TA
creator: Grandis, JR
description: Background Protein tyrosine phosphatase receptor type D (PTPRD) is a putative tumor suppressor in several cancers including head and neck squamous cell carcinoma (HNSCC). STAT3 is a frequently hyperactivated oncogene in HNSCC. As STAT3 is a direct substrate of PTPRD, we sought to determine the genetic or epigenetic alterations of PTPRD that contribute to overactive STAT3 in HNSCC. Methods We analyzed data from The Cancer Genome Atlas (TCGA) and our previous whole-exome sequencing study and summarized the mutation, methylation, and copy number status of PTPRD in HNSCC and other cancers. In vitro studies involved standard transfection and MTT protocols, as well as methylation-specific PCR. Results Our findings indicate that PTPRD mutation, rather thanmethylation or copy number alteration, is the primary mechanism by which PTPRD function is lost in HNSCC.We demonstrate that overexpression of wild-type PTPRD in HNSCC cells significantly inhibits growth and STAT3 activation while PTPRD mutants do not, suggesting thatmutation may lead to loss of function and subsequent hyper-phosphorylation of PTPRD substrates, especially STAT3. Importantly, we determined that HNSCC cells harboring an endogenous PTPRD mutation are more sensitive to STAT3 blockade than PTPRD wild-type cells.We additionally found that PTPRD mRNA expression does not correlate with pSTAT3 expression, suggesting that alterations that manifest through altered mRNA expression, including hypermethylation and gene copy number alterations, do not significantly contribute to STAT3 overactivation in HNSCC. Copyright:
date: 2015-08-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28397/1/journal.pone.0135750.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28397/3/licence.txt
identifier:   Peyser, ND and Du, Y and Li, H and Lui, V and Xiao, X and Chan, TA and Grandis, JR  (2015) Loss-of-function PTPRD mutations lead to increased STAT3 activation and sensitivity to STAT3 inhibition in head and neck cancer.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0135750

relation: http://d-scholarship-dev.library.pitt.edu/28399/
title: The role of aerobic fitness in cortical thickness and mathematics achievement in preadolescent children
creator: Chaddock-Heyman, L
creator: Erickson, KI
creator: Kienzler, C
creator: King, M
creator: Pontifex, MB
creator: Raine, LB
creator: Hillman, CH
creator: Kramer, AF
description: Growing evidence suggests that aerobic fitness benefits the brain and cognition during childhood. The present study is the first to explore cortical brain structure of higher fit and lower fit 9-and 10-year-old children, and how aerobic fitness and cortical thickness relate to academic achievement. We demonstrate that higher fit children (>70th percentile VO2max) showed decreased gray matter thickness in superior frontal cortex, superior temporal areas, and lateral occipital cortex, coupled with better mathematics achievement, compared to lower fit children (<30th percentile VO2max). Furthermore, cortical gray matter thinning in anterior and superior frontal areas was associated with superior arithmetic performance. Together, these data add to our knowledge of the biological markers of school achievement, particularly mathematics achievement, and raise the possibility that individual differences in aerobic fitness play an important role in cortical gray matter thinning during brain maturation. The establishment of predictors of academic performance is key to helping educators focus on interventions to maximize learning and success across the lifespan.
date: 2015-08-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28399/1/journal.pone.0134115.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28399/3/licence.txt
identifier:   Chaddock-Heyman, L and Erickson, KI and Kienzler, C and King, M and Pontifex, MB and Raine, LB and Hillman, CH and Kramer, AF  (2015) The role of aerobic fitness in cortical thickness and mathematics achievement in preadolescent children.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134115

relation: http://d-scholarship-dev.library.pitt.edu/28400/
title: Microbial ligand costimulation drives neutrophilic steroid-refractory asthma
creator: Hadebe, S
creator: Kirstein, F
creator: Fierens, K
creator: Chen, K
creator: Drummond, RA
creator: Vautier, S
creator: Sajaniemi, S
creator: Murray, G
creator: Williams, DL
creator: Redelinghuys, P
creator: Reinhart, TA
creator: Junecko, BAF
creator: Kolls, JK
creator: Lambrecht, BN
creator: Brombacher, F
creator: Brown, GD
creator: Ryffel, B
description: Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these micro-bial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.
date: 2015-08-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28400/1/journal.pone.0134219.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28400/3/licence.txt
identifier:   Hadebe, S and Kirstein, F and Fierens, K and Chen, K and Drummond, RA and Vautier, S and Sajaniemi, S and Murray, G and Williams, DL and Redelinghuys, P and Reinhart, TA and Junecko, BAF and Kolls, JK and Lambrecht, BN and Brombacher, F and Brown, GD and Ryffel, B  (2015) Microbial ligand costimulation drives neutrophilic steroid-refractory asthma.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134219

relation: http://d-scholarship-dev.library.pitt.edu/29213/
title: The PROMIS of QALYs
creator: Hanmer, J
creator: Feeny, D
creator: Fischhoff, B
creator: Hays, RD
creator: Hess, R
creator: Pilkonis, PA
creator: Revicki, DA
creator: Roberts, MS
creator: Tsevat, J
creator: Yu, L
description: Measuring health and health-related quality of life (HRQoL) is important for tracking the health of individuals and populations over time. Generic HRQoL measures allow for comparison across health conditions. One form of generic HRQoL measures are profile measures, which provide a description of health across several different domains (such as physical functioning, depression, and pain). Recent advances in health profile measurement include the development of measures based on item response theory. The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been constructed using this theory. Another form of generic HRQoL measures are utility measures, which assess the value of health states. Multi-attribute utility theory provides a framework for valuing disparate domains of health and aggregating them into a single preference-based score. Such a score provides an overall measure of health outcomes as well as a quality of life weight for use in decision analyses and cost-effectiveness analyses. Developing a utility score for PROMIS® would allow simultaneous estimation of both health profile and utility scores using a single measure. The purpose of this paper is to provide a roadmap of the methodological steps necessary to create such a scoring system.
date: 2015-08-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29213/1/art%253A10.1186%252Fs12955-015-0321-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29213/7/licence.txt
identifier:   Hanmer, J and Feeny, D and Fischhoff, B and Hays, RD and Hess, R and Pilkonis, PA and Revicki, DA and Roberts, MS and Tsevat, J and Yu, L  (2015) The PROMIS of QALYs.  Health and Quality of Life Outcomes, 13 (1).       
relation: 10.1186/s12955-015-0321-6

relation: http://d-scholarship-dev.library.pitt.edu/28401/
title: A teach-discover-treat application of ZincPharmer: An online interactive pharmacophore modeling and virtual screening tool
creator: Koes, DR
creator: Pabon, NA
creator: Deng, X
creator: Phillips, MA
creator: Camacho, CJ
description: The 2012 Teach-Discover-Treat (TDT) community-wide experiment provided a unique opportunity to test prospective virtual screening protocols targeting the anti-malarial target dihydroorotate dehydrogenase (DHODH). Facilitated by ZincPharmer, an open access online interactive pharmacophore search of the ZINC database, the experience resulted in the development of a novel classification scheme that successfully predicted the bound structure of a non-triazolopyrimidine inhibitor, as well as an overall hit rate of 27% of tested active compounds from multiple novel chemical scaffolds. The general approach entailed exhaustively building and screening sparse pharmacophore models comprising of a minimum of three features for each bound ligand in all available DHODH co-crystals and iteratively adding features that increased the number of known binders returned by the query. Collectively, the TDT experiment provided a unique opportunity to teach computational methods of drug discovery, develop innovative methodologies and prospectively discover new compounds active against DHODH. Copyright:
date: 2015-08-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28401/1/journal.pone.0134697.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28401/3/licence.txt
identifier:   Koes, DR and Pabon, NA and Deng, X and Phillips, MA and Camacho, CJ  (2015) A teach-discover-treat application of ZincPharmer: An online interactive pharmacophore modeling and virtual screening tool.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134697

relation: http://d-scholarship-dev.library.pitt.edu/28403/
title: Analysis of feedback mechanisms with unknown delay using sparse multivariate autoregressive method
creator: Ip, EH
creator: Zhang, Q
creator: Sowinski, T
creator: Simpson, SL
description: This paper discusses the study of two interacting processes in which a feedback mechanism exists between the processes. The study was motivated by problems such as the circadian oscillation of gene expression where two interacting protein transcriptions form both negative and positive feedback loops with long delays to equilibrium. Traditionally, data of this type could be examined using autoregressive analysis. However, in circadian oscillation the order of an autoregressive model cannot be determined a priori. We propose a sparse multivariate autoregressive method that incorporates mixed linear effects into regression analysis, and uses a forward-backward greedy search algorithm to select nonzero entries in the regression coefficients, the number of which is constrained not to exceed a pre-specified number. A small simulation study provides preliminary evidence of the validity of the method. Besides the circadian oscillation example, an additional example of blood pressure variations using data from an intervention study is used to illustrate the method and the interpretation of the results obtained from the sparse matrix method. These applications demonstrate how sparse representation can be used for handling high dimensional variables that feature dynamic, reciprocal relationships.
date: 2015-08-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28403/1/journal.pone.0131371.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28403/3/licence.txt
identifier:   Ip, EH and Zhang, Q and Sowinski, T and Simpson, SL  (2015) Analysis of feedback mechanisms with unknown delay using sparse multivariate autoregressive method.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0131371

relation: http://d-scholarship-dev.library.pitt.edu/29215/
title: The molecular landscape of premenopausal breast cancer
creator: Liao, S
creator: Hartmaier, RJ
creator: McGuire, KP
creator: Puhalla, SL
creator: Luthra, S
creator: Chandran, UR
creator: Ma, T
creator: Bhargava, R
creator: Modugno, F
creator: Davidson, NE
creator: Benz, S
creator: Lee, AV
creator: Tseng, GC
creator: Oesterreich, S
description: Introduction: Breast cancer in premenopausal women (preM) is frequently associated with worse prognosis compared to that in postmenopausal women (postM), and there is evidence that preM estrogen receptor-positive (ER+) tumors may respond poorly to endocrine therapy. There is, however, a paucity of studies characterizing molecular alterations in premenopausal tumors, a potential avenue for personalizing therapy for this group of women. Methods: Using TCGA and METABRIC databases, we analyzed gene expression, copy number, methylation, somatic mutation, and reverse-phase protein array data in breast cancers from >2,500 preM and postM women. Results: PreM tumors showed unique gene expression compared to postM tumors, however, this difference was limited to ER+ tumors. ER+ preM tumors showed unique DNA methylation, copy number and somatic mutations. Integrative pathway analysis revealed that preM tumors had elevated integrin/laminin and EGFR signaling, with enrichment for upstream TGFβ-regulation. Finally, preM tumors showed three different gene expression clusters with significantly different outcomes. Conclusion: Together these data suggest that ER+ preM tumors have distinct molecular characteristics compared to ER+ postM tumors, particularly with respect to integrin/laminin and EGFR signaling, which may represent therapeutic targets in this subgroup of breast cancers.
date: 2015-08-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29215/1/art%253A10.1186%252Fs13058-015-0618-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29215/7/licence.txt
identifier:   Liao, S and Hartmaier, RJ and McGuire, KP and Puhalla, SL and Luthra, S and Chandran, UR and Ma, T and Bhargava, R and Modugno, F and Davidson, NE and Benz, S and Lee, AV and Tseng, GC and Oesterreich, S  (2015) The molecular landscape of premenopausal breast cancer.  Breast Cancer Research, 17 (1).   ISSN 1465-5411     
relation: 10.1186/s13058-015-0618-8

relation: http://d-scholarship-dev.library.pitt.edu/29216/
title: CNTN6 copy number variations in 14 patients: A possible candidate gene for neurodevelopmental and neuropsychiatric disorders
creator: Hu, J
creator: Liao, J
creator: Sathanoori, M
creator: Kochmar, S
creator: Sebastian, J
creator: Yatsenko, SA
creator: Surti, U
description: Background: Neurodevelopmental disorders are impairments of brain function that affect emotion, learning, and memory. Copy number variations of contactin genes (CNTNs), including CNTN3, CNTN4, CNTN5, and CNTN6, have been suggested to be associated with these disorders. However, phenotypes have been reported in only a handful of patients with copy number variations involving CNTNs. Methods: From January 2009 to January 2013, 3724 patients ascertained through the University of Pittsburgh Medical Center were referred to our laboratory for clinical array comparative genomic hybridization testing. We screened this cohort of patients to identify individuals with the 3p26.3 copy number variations involving the CNTN6 gene, and then retrospectively reviewed the clinical information and family history of these patients to determine the association between the 3p26.3 copy number variations and neurodevelopmental disorders. Results: Fourteen of the 3724 patients had 3p26.3 copy number variations involving the CNTN6 gene. Thirteen of the 14 patients with these CNTN6 copy number variations presented with various neurodevelopmental disorders including developmental delay, autistic spectrum disorders, seizures and attention deficit hyperactivity disorder. Family history was available for 13 of the 14 patients. Twelve of the thirteen families have multiple members with neurodevelopmental and neuropsychiatric disorders including attention deficit hyperactivity disorder, seizures, autism spectrum disorder, intellectual disability, schizophrenia, depression, anxiety, learning disability, and bipolar disorder. Conclusions: Our findings suggest that deletion or duplication of the CNTN6 gene is associated with a wide spectrum of neurodevelopmental behavioral disorders.
date: 2015-08-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29216/1/art%253A10.1186%252Fs11689-015-9122-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29216/7/licence.txt
identifier:   Hu, J and Liao, J and Sathanoori, M and Kochmar, S and Sebastian, J and Yatsenko, SA and Surti, U  (2015) CNTN6 copy number variations in 14 patients: A possible candidate gene for neurodevelopmental and neuropsychiatric disorders.  Journal of Neurodevelopmental Disorders, 7 (1).   ISSN 1866-1947     
relation: 10.1186/s11689-015-9122-9

relation: http://d-scholarship-dev.library.pitt.edu/29222/
title: Cluster randomized controlled trial protocol: Addressing reproductive coercion in health settings (ARCHES)
creator: Tancredi, DJ
creator: Silverman, JG
creator: Decker, MR
creator: McCauley, HL
creator: Anderson, HA
creator: Jones, KA
creator: Ciaravino, S
creator: Hicks, A
creator: Raible, C
creator: Zelazny, S
creator: James, L
creator: Miller, E
description: Background: Women ages 16-29 utilizing family planning clinics for medical services experience higher rates of intimate partner violence (IPV) and reproductive coercion (RC) than their same-age peers, increasing risk for unintended pregnancy and related poor reproductive health outcomes. Brief interventions integrated into routine family planning care have shown promise in reducing risk for RC, but longer-term intervention effects on partner violence victimization, RC, and unintended pregnancy have not been examined. Methods/Design: The 'Addressing Reproductive Coercion in Health Settings (ARCHES)' Intervention Study is a cluster randomized controlled trial evaluating the effectiveness of a brief, clinician-delivered universal education and counseling intervention to reduce IPV, RC and unintended pregnancy compared to standard-of-care in family planning clinic settings. The ARCHES intervention was refined based on formative research. Twenty five family planning clinics were randomized (in 17 clusters) to either a three hour training for all family planning clinic staff on how to deliver the ARCHES intervention or to a standard-of-care control condition. All women ages 16-29 seeking care in these family planning clinics were eligible to participate. Consenting clients use laptop computers to answer survey questions immediately prior to their clinic visit, a brief exit survey immediately after the clinic visit, a first follow up survey 12-20 weeks after the baseline visit (T2), and a final survey 12 months after the baseline (T3). Medical record chart review provides additional data about IPV and RC assessment and disclosure, sexual and reproductive health diagnoses, and health care utilization. Of 4009 women approached and determined to be eligible based on age (16-29 years old), 3687 (92 % participation) completed the baseline survey and were included in the sample. Discussion: The ARCHES Intervention Study is a community-partnered study designed to provide arigorous assessment of the short (3-4 months) and long-term (12 months) effects of a brief, clinician-delivered universal education and counseling intervention to reduce IPC, RC and unintended pregnancy in family planning clinic settings. The trial features a cluster randomized controlled trial design, a comprehensive data collection schedule and a large sample size with excellent retention. Trial Registration: ClinicialTrials.gov NCT01459458 Registered 10 October 2011.
date: 2015-08-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29222/1/art%253A10.1186%252Fs12905-015-0216-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29222/7/licence.txt
identifier:   Tancredi, DJ and Silverman, JG and Decker, MR and McCauley, HL and Anderson, HA and Jones, KA and Ciaravino, S and Hicks, A and Raible, C and Zelazny, S and James, L and Miller, E  (2015) Cluster randomized controlled trial protocol: Addressing reproductive coercion in health settings (ARCHES).  BMC Women's Health, 15 (1).       
relation: 10.1186/s12905-015-0216-z

relation: http://d-scholarship-dev.library.pitt.edu/28406/
title: Combined PDGFR and HDAC inhibition overcomes PTEN disruption in Chordoma
creator: Lee, DH
creator: Zhang, Y
creator: Kassam, AB
creator: Park, MJ
creator: Gardner, P
creator: Prevedello, D
creator: Henry, S
creator: Horbinski, C
creator: Beumer, JH
creator: Tawbi, H
creator: Williams, BJ
creator: Shaffrey, ME
creator: Egorin, MJ
creator: Abounader, R
creator: Park, DM
description: Background: The majority of chordomas show activation of the platelet-derived growth factor receptor (PDGFR). Based on in vitro intertumoral variation in response to recombinant PDGF protein and PDGFR inhibition, and variable tumor response to imatinib, we hypothesized that chordomas resistant to PDGFR inhibition may possess downstream activation of the pathway. Methods: Molecular profiling was performed on 23 consecutive chordoma primary tissue specimens. Primary cultures established from 20 of the 23 specimens, and chordoma cell lines, UCH-1 and UCH-2, were used for in vitro experiments. Results: Loss of heterozygosity (LOH) at the phosphatase and tensin homolog (PTEN) locus was observed in 6 specimens (26%). PTEN disruption statistically correlated with increased Ki-67 proliferation index, an established marker of poor outcome for chordoma. Compared to wild type, PTEN deficient chordomas displayed increased proliferative rate, and responded less favorably to PDGFR inhibition. PTEN gene restoration abrogated this growth advantage. Chordomas are characterized by intratumoral hypoxia and local invasion, and histone deacetylase (HDAC) inhibitors are capable of attenuating both hypoxic signaling and cell migration. The combination of PDGFR and HDAC inhibition effectively disrupted growth and invasion of PTEN deficient chordoma cells. Conclusions: Loss of heterozygosity of the PTEN gene seen in a subset of chordomas is associated with aggressive in vitro behavior and strongly correlates with increased Ki-67 proliferative index. Combined inhibition of PDGFR and HDAC attenuates proliferation and invasion in chordoma cells deficient for PTEN.
date: 2015-08-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28406/1/journal.pone.0134426.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28406/3/licence.txt
identifier:   Lee, DH and Zhang, Y and Kassam, AB and Park, MJ and Gardner, P and Prevedello, D and Henry, S and Horbinski, C and Beumer, JH and Tawbi, H and Williams, BJ and Shaffrey, ME and Egorin, MJ and Abounader, R and Park, DM  (2015) Combined PDGFR and HDAC inhibition overcomes PTEN disruption in Chordoma.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134426

relation: http://d-scholarship-dev.library.pitt.edu/29223/
title: MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet
creator: He, J
creator: Quintana, MT
creator: Sullivan, J
creator: Parry, T
creator: Grevengoed, T
creator: Schisler, JC
creator: Hill, JA
creator: Yates, CC
creator: Mapanga, RF
creator: Essop, MF
creator: Stansfield, WE
creator: Bain, JR
creator: Newgard, CB
creator: Muehlbauer, MJ
creator: Han, Y
creator: Clarke, BA
creator: Willis, MS
description: Background: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARaα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2-/- hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. Methods: MuRF2-/- mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARaα, PPARβ, and PPARγ1-regulated mRNA expression. Results: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2-/- hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2-/- hearts had significantly increased PPARaα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2's regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARaα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. Conclusions: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARaα and PPARγ1 activities in vivo via post-translational modification without degradation.
date: 2015-08-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29223/1/art%253A10.1186%252Fs12933-015-0252-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29223/7/licence.txt
identifier:   He, J and Quintana, MT and Sullivan, J and Parry, T and Grevengoed, T and Schisler, JC and Hill, JA and Yates, CC and Mapanga, RF and Essop, MF and Stansfield, WE and Bain, JR and Newgard, CB and Muehlbauer, MJ and Han, Y and Clarke, BA and Willis, MS  (2015) MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet.  Cardiovascular Diabetology, 14 (1).       
relation: 10.1186/s12933-015-0252-x

relation: http://d-scholarship-dev.library.pitt.edu/28407/
title: A three-tiered study of differences in murine intrahost immune response to multiple pneumococcal strains
creator: Mochan-Keef, E
creator: Swigon, D
creator: Ermentrout, GB
creator: Clermont, G
description: We apply a previously developed 4-variable ordinary differential equation model of in-host immune response to pneumococcal pneumonia to study the variability of the immune response of MF1 mice and to explore bacteria-driven differences in disease progression and outcome. In particular, we study the immune response to D39 strain of bacteria missing portions of the pneumolysin protein controlling either the hemolytic activity or complement-activating activity, the response to D39 bacteria deficient in either neuraminidase A or B, and the differences in the response to D39 (serotype 2), 0100993 (serotype 3), and TIGR4 (serotype 4) bacteria. The model accurately reproduces infection kinetics in all cases and provides information about which mechanisms in the immune response have the greatest effect in each case. Results suggest that differences in the ability of bacteria to defeat immune response are primarily due to the ability of the bacteria to elude nonspecific clearance in the lung tissue as well as the ability to create damage to the lung epithelium.
date: 2015-08-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28407/1/journal.pone.0134012.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28407/3/licence.txt
identifier:   Mochan-Keef, E and Swigon, D and Ermentrout, GB and Clermont, G  (2015) A three-tiered study of differences in murine intrahost immune response to multiple pneumococcal strains.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0134012

relation: http://d-scholarship-dev.library.pitt.edu/28408/
title: Partial loss of genomic imprinting reveals important roles for Kcnq1 and Peg10 imprinted domains in placental development
creator: Koppes, E
creator: Himes, KP
creator: Chaillet, JR
description: Mutations in imprinted genes or their imprint control regions (ICRs) produce changes in imprinted gene expression and distinct abnormalities in placental structure, indicating the importance of genomic imprinting to placental development. We have recently shown that a very broad spectrum of placental abnormalities associated with altered imprinted gene expression occurs in the absence of the oocyte-derived DNMT1o cytosine methyltransferase, which normally maintains parent-specific imprinted methylation during preimplantation. The absence of DNMT1o partially reduces inherited imprinted methylation while retaining the genetic integrity of imprinted genes and their ICRs. Using this novel system, we undertook a broad and inclusive approach to identifying key ICRs involved in placental development by correlating loss of imprinted DNA methylation with abnormal placental phenotypes in a mid-gestation window (E12.5-E15.5). To these ends we measured DNA CpG methylation at 15 imprinted gametic differentially methylated domains (gDMDs) that overlap known ICRs using EpiTYPER-mass array technology, and linked these epigenetic measurements to histomorphological defects. Methylation of some imprinted gDMDs, most notably Dlk1, was nearly normal in mid-gestation DNMT1o-deficient placentas, consistent with the notion that cells having lost methylation on these DMDs do not contribute significantly to placental development. Most imprinted gDMDs however showed a wide range of methylation loss among DNMT1o-deficient placentas. Two striking associations were observed. First, loss of DNA methylation at the Peg10 imprinted gDMD associated with decreased embryonic viability and decreased labyrinthine volume. Second, loss of methylation at the Kcnq1 imprinted gDMD was strongly associated with trophoblast giant cell (TGC) expansion. We conclude that the Peg10 and Kcnq1 ICRs are key regulators of mid-gestation placental function. Copyright:
date: 2015-08-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28408/1/journal.pone.0135202.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28408/3/licence.txt
identifier:   Koppes, E and Himes, KP and Chaillet, JR  (2015) Partial loss of genomic imprinting reveals important roles for Kcnq1 and Peg10 imprinted domains in placental development.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0135202

relation: http://d-scholarship-dev.library.pitt.edu/28030/
title: Curatorial Practice as Production of Visual &amp; Spatial Knowledge: Panel Discussion, October 4, 2014
creator: Scalissi, Nicole
creator: Langmead, Alison
creator: Smith, Terry
creator: Byers, Dan
creator: Morton, Cynthia
description: <jats:p> The following is a transcription of a conversation between curators of art, science, and digital data about how their practice creates knowledge in their respective fields. Drawn from Pittsburgh’s rich institutional resources, the panelists include Dan Byers, (then) Richard Armstrong Curator of Contemporary Art, Carnegie Museum of Art; Dr. Alison Langmead, Director, Visual Media Workshop, Department of History of Art and Architecture, and Assistant Professor, School of Information Scienes, University of Pittsburgh; Dr. Cynthia Morton, Associate Curator of Botany, Carnegie Museum of Natural History; and Dr. Terry Smith, Andrew W. Mellon Professor of Contemporary Art History and Theory, University of Pittsburgh. Moderated by Nicole Scalissi, PhD candidate, Department of History of Art and Architecture, University of Pittsburgh. The panel took place as a part of Debating Visual Knowledge, a symposium organized by graduate students in Information Science and History of Art and Architecture at the University of Pittsburgh, October 3-5, 2014. The transcription has been edited for clarity.Curatorial Practice as Production of Visual &amp; Spatial Knowledge</jats:p>
publisher: University Library System, University of Pittsburgh
date: 2015-08-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28030/1/151-570-1-PB.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28030/4/licence.txt
identifier:   Scalissi, Nicole and Langmead, Alison and Smith, Terry and Byers, Dan and Morton, Cynthia  (2015) Curatorial Practice as Production of Visual &amp; Spatial Knowledge: Panel Discussion, October 4, 2014.  Contemporaneity: Historical Presence in Visual Culture, 4.  143 - 157.      
relation: 10.5195/contemp.2015.151

relation: http://d-scholarship-dev.library.pitt.edu/28031/
title: Curatorial Practice as Production of Visual and Spatial Knowledge: Panelists Respond
creator: Langmead, Alison
creator: Byers, Dan
creator: Morton, Cynthia
description: <jats:p> Three participants in the panel “Curatorial Practice as Production of Visual and Spatial Knowledge” reflect upon the ideas raised in their discussion about curating, both in their respective fields and as a general practice. The panel was a part of Debating Visual Knowledge, a symposium organized by graduate students in Information Science and History of Art and Architecture at the University of Pittsburgh, October 3–5, 2014. A transcription of the panel is available in this issue. </jats:p>
publisher: University Library System, University of Pittsburgh
date: 2015-08-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28031/1/152-571-1-PB.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28031/4/licence.txt
identifier:   Langmead, Alison and Byers, Dan and Morton, Cynthia  (2015) Curatorial Practice as Production of Visual and Spatial Knowledge: Panelists Respond.  Contemporaneity: Historical Presence in Visual Culture, 4.  158 - 163.      
relation: 10.5195/contemp.2015.152

relation: http://d-scholarship-dev.library.pitt.edu/28409/
title: Dexmedetomidine reduces shivering during mild hypothermia in waking subjects
creator: Callaway, CW
creator: Elmer, J
creator: Guyette, FX
creator: Molyneaux, BJ
creator: Anderson, KB
creator: Empey, PE
creator: Gerstel, SJ
creator: Holquist, K
creator: Repine, MJ
creator: Rittenberger, JC
description: Background and Purpose Reducing body temperature can prolong tolerance to ischemic injury such as stroke or myocardial infarction, but is difficult and uncomfortable in awake patients because of shivering. We tested the efficacy and safety of the alpha-2-adrenergic agonist dexmedetomidine for suppressing shivering induced by a rapid infusion of cold intravenous fluids. Methods Ten subjects received a rapid intravenous infusion of two liters of cold (4°C) isotonic saline on two separate test days, and we measured their core body temperature, shivering, hemodynamics and sedation for two hours. On one test day, fluid infusion was preceded by placebo infusion. On the other test day, fluid infusion was preceded by 1.0 μg/kg bolus of dexmedetomidine over 10 minutes. Results All ten subjects experienced shivering on placebo days, with shivering beginning at a mean (SD) temperature of 36.6 (0.3)°C. The mean lowest temperature after placebo was 36.0 (0.3) °C (range 35.7-36.5°C). Only 3/10 subjects shivered on dexmedetomidine days, and the mean lowest temperature was 35.7 (0.4) °C (range 35.0-36.3°C). Temperature remained below 36°C for the full two hours in 6/10 subjects. After dexmedetomidine, subjects had moderate sedation and a mean 26 (13) mmHg reduction in blood pressure that resolved within 90 minutes. Heart rate declined a mean 23 (11) bpm after both placebo and dexmedetomidine. Dexmedetomidine produced no respiratory depression. Conclusion Dexmedetomidine decreases shivering in normal volunteers. This effect is associated with decreased systolic blood pressure and sedation, but no respiratory depression. Copyright:
date: 2015-08-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28409/1/journal.pone.0129709.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28409/3/licence.txt
identifier:   Callaway, CW and Elmer, J and Guyette, FX and Molyneaux, BJ and Anderson, KB and Empey, PE and Gerstel, SJ and Holquist, K and Repine, MJ and Rittenberger, JC  (2015) Dexmedetomidine reduces shivering during mild hypothermia in waking subjects.  PLoS ONE, 10 (8).       
relation: 10.1371/journal.pone.0129709

relation: http://d-scholarship-dev.library.pitt.edu/28511/
title: Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight, Mutually Exclusive Sets
creator: Lu, S
creator: Lu, KN
creator: Cheng, SY
creator: Hu, B
creator: Ma, X
creator: Nystrom, N
creator: Lu, X
description: An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms and the heterogeneity of cancers. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this characteristic has been utilized as an objective function to guide the search for driver mutations within a pathway. However, mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs. First, we identify the perturbed cellular signals by mining the gene expression data. Next, we search for a set of SGA events that carries strong information with respect to such perturbed signals while exhibiting mutual exclusivity. Finally, we design and implement an efficient exact algorithm to solve an NP-hard problem encountered in our approach. We apply this framework to the ovarian and glioblastoma tumor data available at the TCGA database, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways.
date: 2015-08-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28511/1/journal.pcbi.1004257.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28511/3/licence.txt
identifier:   Lu, S and Lu, KN and Cheng, SY and Hu, B and Ma, X and Nystrom, N and Lu, X  (2015) Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight, Mutually Exclusive Sets.  PLoS Computational Biology, 11 (8).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004257

relation: http://d-scholarship-dev.library.pitt.edu/28512/
title: Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses
creator: Ocker, GK
creator: Litwin-Kumar, A
creator: Doiron, B
description: The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.
date: 2015-08-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28512/1/journal.pcbi.1004458.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28512/3/licence.txt
identifier:   Ocker, GK and Litwin-Kumar, A and Doiron, B  (2015) Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses.  PLoS Computational Biology, 11 (8).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004458

relation: http://d-scholarship-dev.library.pitt.edu/28410/
title: C-Myc and AMPK control cellular energy levels by cooperatively regulating mitochondrial structure and function
creator: Edmunds, LR
creator: Sharma, L
creator: Wang, H
creator: Kang, A
creator: D'Souza, S
creator: Lu, J
creator: McLaughlin, M
creator: Dolezal, JM
creator: Gao, X
creator: Weintraub, ST
creator: Ding, Y
creator: Zeng, X
creator: Yates, N
creator: Prochownik, EV
description: The c-Myc (Myc) oncoprotein and AMP-activated protein kinase (AMPK) regulate glycolysis and oxidative phosphorylation (Oxphos) although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT) and ampk-/-(KO) murine embryo fibroblasts (MEFs). KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER) fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS)-based survey capable of quantifying ∼40% of all mitochondrial proteins, showed about 15% of them to be AMPK-and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions. Copyright:
date: 2015-07-31
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28410/1/journal.pone.0134049.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28410/3/licence.txt
identifier:   Edmunds, LR and Sharma, L and Wang, H and Kang, A and D'Souza, S and Lu, J and McLaughlin, M and Dolezal, JM and Gao, X and Weintraub, ST and Ding, Y and Zeng, X and Yates, N and Prochownik, EV  (2015) C-Myc and AMPK control cellular energy levels by cooperatively regulating mitochondrial structure and function.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0134049

relation: http://d-scholarship-dev.library.pitt.edu/29205/
title: Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice.
creator: Pisciotta, Alessandra
creator: Riccio, Massimo
creator: Carnevale, Gianluca
creator: Lu, Aiping
creator: De Biasi, Sara
creator: Gibellini, Lara
creator: La Sala, Giovanni B
creator: Bruzzesi, Giacomo
creator: Ferrari, Adriano
creator: Huard, Johnny
creator: De Pol, Anto
description: INTRODUCTION: Duchenne muscular dystrophy (DMD), caused by a lack of the functional structural protein dystrophin, leads to severe muscle degeneration where the patients are typically wheelchair-bound and die in their mid-twenties from cardiac or respiratory failure or both. The aim of this study was to investigate the potential of human dental pulp stem cells (hDPSCs) and human amniotic fluid stem cells (hAFSCs) to differentiate toward a skeletal myogenic lineage using several different protocols in order to determine the optimal conditions for achieving myogenic commitment and to subsequently evaluate their contribution in the improvement of the pathological features associated with dystrophic skeletal muscle when intramuscularly injected into mdx/SCID mice, an immune-compromised animal model of DMD. METHODS: Human DPSCs and AFSCs were differentiated toward myogenic lineage in vitro through the direct co-culture with a myogenic cell line (C2C12 cells) and through a preliminary demethylation treatment with 5-Aza-2'-deoxycytidine (5-Aza), respectively. The commitment and differentiation of both hDPSCs and hAFSCs were evaluated by immunofluorescence and Western blot analysis. Subsequently, hDPSCs and hAFSCs, preliminarily demethylated and pre-differentiated toward a myogenic lineage for 2 weeks, were injected into the dystrophic gastrocnemius muscles of mdx/SCID mice. After 1, 2, and 4 weeks, the gastrocnemius muscles were taken for immunofluorescence and histological analyses. RESULTS: Both populations of cells engrafted within the host muscle of mdx/SCID mice and through a paracrine effect promoted angiogenesis and reduced fibrosis, which eventually led to an improvement of the histopathology of the dystrophic muscle. CONCLUSION: This study shows that hAFSCs and hDPSCs represent potential sources of stem cells for translational strategies to improve the histopathology and potentially alleviate the muscle weakness in patients with DMD.
date: 2015-07-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29205/1/art%253A10.1186%252Fs13287-015-0141-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29205/7/licence.txt
identifier:   Pisciotta, Alessandra and Riccio, Massimo and Carnevale, Gianluca and Lu, Aiping and De Biasi, Sara and Gibellini, Lara and La Sala, Giovanni B and Bruzzesi, Giacomo and Ferrari, Adriano and Huard, Johnny and De Pol, Anto  (2015) Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice.  Stem Cell Res Ther, 6.  156 - ?.      
relation: 10.1186/s13287-015-0141-y
language: eng

relation: http://d-scholarship-dev.library.pitt.edu/28411/
title: Fluorescence polarization screening assays for small molecule allosteric modulators of ABL kinase function
creator: Grover, P
creator: Shi, H
creator: Baumgartner, M
creator: Camacho, CJ
creator: Smithgall, TE
description: The ABL protein-tyrosine kinase regulates intracellular signaling pathways controlling diverse cellular processes and contributes to several forms of cancer. The kinase activity of ABL is repressed by intramolecular interactions involving its regulatory Ncap, SH3 and SH2 domains. Small molecules that allosterically regulate ABL kinase activity through its noncatalytic domains may represent selective probes of ABL function. Here we report a screening assay for chemical modulators of ABL kinase activity that target the regulatory interaction of the SH3 domain with the SH2-kinase linker. This fluorescence polarization (FP) assay is based on a purified recombinant ABL protein consisting of the N-cap, SH3 and SH2 domains plus the SH2-kinase linker (N32L protein) and a short fluorescein-labeled probe peptide that binds to the SH3 domain. In assay development experiments, we found that the probe peptide binds to the recombinant ABL N32L protein in vitro, producing a robust FP signal that can be competed with an excess of unlabeled peptide. The FP signal is not observed with control N32L proteins bearing either an inactivating mutation in the SH3 domain or enhanced SH3:linker interaction. A pilot screen of 1200 FDA-approved drugs identified four compounds that specifically reduced the FP signal by at least three standard deviations from the untreated controls. Secondary assays showed that one of these hit compounds, the antithrombotic drug dipyridamole, enhances ABL kinase activity in vitro to a greater extent than the previously described ABL agonist, DPH. Docking studies predicted that this compound binds to a pocket formed at the interface of the SH3 domain and the linker, suggesting that it activates ABL by disrupting this regulatory interaction. These results show that screening assays based on the non-catalytic domains of ABL can identify allosteric small molecule regulators of kinase function, providing a new approach to selective drug discovery for this important kinase system.
date: 2015-07-29
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28411/1/journal.pone.0133590.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28411/3/licence.txt
identifier:   Grover, P and Shi, H and Baumgartner, M and Camacho, CJ and Smithgall, TE  (2015) Fluorescence polarization screening assays for small molecule allosteric modulators of ABL kinase function.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0133590

relation: http://d-scholarship-dev.library.pitt.edu/29225/
title: Ramucirumab, another anti-angiogenic agent for metastatic colorectal cancer in second-line setting - Its impact on clinical practice
creator: Goel, G
creator: Sun, W
description: The recent FDA approval of ramucirumab (RAISE trial) has added a third agent to our existing armamentarium of angiogenesis inhibitors (bevacizumab and ziv-aflibercept) for the second-line treatment of metastatic colorectal cancer, which may have some impacts in the current clinic practice.
date: 2015-07-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29225/1/art%253A10.1186%252Fs13045-015-0183-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29225/7/licence.txt
identifier:   Goel, G and Sun, W  (2015) Ramucirumab, another anti-angiogenic agent for metastatic colorectal cancer in second-line setting - Its impact on clinical practice.  Journal of Hematology and Oncology, 8 (1).       
relation: 10.1186/s13045-015-0183-8

relation: http://d-scholarship-dev.library.pitt.edu/29226/
title: Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations
creator: Zou, N
creator: Yang, L
creator: Chen, L
creator: Li, T
creator: Jin, T
creator: Peng, H
creator: Zhang, S
creator: Wang, D
creator: Li, R
creator: Liu, C
creator: Jiang, J
creator: Wang, L
creator: Liang, W
creator: Hu, J
creator: Li, S
creator: Wu, C
creator: Cui, X
creator: Chen, Y
creator: Li, F
description: Background: The role of human papillomavirus (HPV) may be involved in the development of esophageal cancer (EC) and the polymorphic immune response gene transporter associated with antigen processing (TAP) may be involved in HPV persistence and subsequent cancer carcinogenesis. The current study aims to provide association evidence for HPV with EC, to investigate TAP1 polymorphisms in EC and assess its association with HPV statuses and EC in Kazakhs. Methods: The HPV genotypes in 361 patients with EC and 66 controls selected from Kazakh population were evaluated using PCR. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect two SNPs of TAP1 in 150 cases comprised of 75 HPV<sup>+</sup> and 75 HPV<sup>-</sup> patients and 283 pure ethnic population of Kazakh and evaluate their associations with susceptibility to EC. A case-to-case comparison based on the genotyping results was conducted to address the function of TAP1 variants in the involvement of HPV. Results: The presence of four HPV genotypes in EC tissues-including HPV 16, 18, 31, 45-was significantly higher at 64.6 % than those in controls at 18.2 % (P∈<∈0.001). Such presence was strongly associated with increased risk of EC (OR 8.196; 95 % CI 4.280-15.964). The infection of HPV16, and multi-infection of 16 and 18 significantly increase the risk for developing EC (OR 4.616, 95 % CI 2.099-10.151; and OR 6.029, 95 % CI 1.395-26.057 respectively). Heterozygote of TAP1 D637G had a significantly higher risk for developing EC (OR 1.626; 95 % CI 1.080-2.449). The odds ratio for HPV infection was significantly lower among carriers of TAP1 D637G polymorphism (OR 0.281; 95 % CI 0.144-0.551). Conclusions: HPV infection exhibits a strong positive association with the risk of EC in Kazakhs. Heterozygote of TAP1 D637G decreases susceptibility to HPV infection in patients with EC but increases susceptibility to EC among the Kazakh populations.
date: 2015-07-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29226/1/art%253A10.1186%252Fs13046-015-0185-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29226/7/licence.txt
identifier:   Zou, N and Yang, L and Chen, L and Li, T and Jin, T and Peng, H and Zhang, S and Wang, D and Li, R and Liu, C and Jiang, J and Wang, L and Liang, W and Hu, J and Li, S and Wu, C and Cui, X and Chen, Y and Li, F  (2015) Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations.  Journal of Experimental and Clinical Cancer Research, 34 (1).       
relation: 10.1186/s13046-015-0185-y

relation: http://d-scholarship-dev.library.pitt.edu/29228/
title: Characterizing functional connectivity patterns during saliva swallows in different head positions
creator: Jestrović, I
creator: Coyle, JL
creator: Sejdić, E
description: Background: The anatomical rationale and efficacy of the chin tuck in improving airway protection for some people with swallowing disorders have been well researched and established. However, there are still open questions regarding whether brain activity for swallowing control is altered while performing this chin-tuck maneuver. Methods: In this study, we collected EEG signals from 55 healthy adults while swallowing in the neutral and chin-tuck head positions. The time-frequency based synchrony measure was used to form brain networks. We investigated both the small-world properties of these brain networks and differences among the constructed brain networks for the two head positions during swallowing tasks. Results: We showed that brain networks for swallowing in both head positions exhibit small-world properties. Furthermore, we showed that swallowing in the chin-tuck head position affects brain networks in the Alpha and Gamma frequency bands. Conclusions: According to these results, we can tell that the parameter of head position should be considered in future investigations which utilize EEG signals during swallowing activity.
date: 2015-07-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29228/1/art%253A10.1186%252Fs12984-015-0049-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29228/7/licence.txt
identifier:   Jestrović, I and Coyle, JL and Sejdić, E  (2015) Characterizing functional connectivity patterns during saliva swallows in different head positions.  Journal of NeuroEngineering and Rehabilitation, 12 (1).       
relation: 10.1186/s12984-015-0049-x

relation: http://d-scholarship-dev.library.pitt.edu/29227/
title: Expression analysis of human adipose-derived stem cells during in vitro differentiation to an adipocyte lineage
creator: Satish, L
creator: Krill-Burger, JM
creator: Gallo, PH
creator: Etages, SD
creator: Liu, F
creator: Philips, BJ
creator: Ravuri, S
creator: Marra, KG
creator: LaFramboise, WA
creator: Kathju, S
creator: Rubin, JP
description: Background: Adipose tissue-derived stromal stem cells (ASCs) represent a promising regenerative resource for soft tissue reconstruction. Although autologous grafting of whole fat has long been practiced, a major clinical limitation of this technique is inconsistent long-term graft retention. To understand the changes in cell function during the transition of ASCs into fully mature fat cells, we compared the transcriptome profiles of cultured undifferentiated human primary ASCs under conditions leading to acquisition of a mature adipocyte phenotype. Methods: Microarray analysis was performed on total RNA extracted from separate ACS isolates of six human adult females before and after 7 days (7 days: early stage) and 21 days (21 days: late stage) of adipocyte differentiation in vitro. Differential gene expression profiles were determined using Partek Genomics Suite Version 6.4 for analysis of variance (ANOVA) based on time in culture. We also performed unsupervised hierarchical clustering to test for gene expression patterns among the three cell populations. Ingenuity Pathway Analysis was used to determine biologically significant networks and canonical pathways relevant to adipogenesis. Results: Cells at each stage showed remarkable intra-group consistency of expression profiles while abundant differences were detected across stages and groups. More than 14,000 transcripts were significantly altered during differentiation while ~6000 transcripts were affected between 7 days and 21 days cultures. Setting a cutoff of +/-two-fold change, 1350 transcripts were elevated while 2929 genes were significantly decreased by 7 days. Comparison of early and late stage cultures revealed increased expression of 1107 transcripts while 606 genes showed significantly reduced expression. In addition to confirming differential expression of known markers of adipogenesis (e.g., FABP4, ADIPOQ, PLIN4), multiple genes and signaling pathways not previously known to be involved in regulating adipogenesis were identified (e.g. POSTN, PPP1R1A, FGF11) as potential novel mediators of adipogenesis. Quantitative RT-PCR validated the microarray results. Conclusions: ASC maturation into an adipocyte phenotype proceeds from a gene expression program that involves thousands of genes. This is the first study to compare mRNA expression profiles during early and late stage adipogenesis using cultured human primary ASCs from multiple patients.
date: 2015-07-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29227/1/art%253A10.1186%252Fs12920-015-0119-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29227/7/licence.txt
identifier:   Satish, L and Krill-Burger, JM and Gallo, PH and Etages, SD and Liu, F and Philips, BJ and Ravuri, S and Marra, KG and LaFramboise, WA and Kathju, S and Rubin, JP  (2015) Expression analysis of human adipose-derived stem cells during in vitro differentiation to an adipocyte lineage.  BMC Medical Genomics, 8 (1).       
relation: 10.1186/s12920-015-0119-8

relation: http://d-scholarship-dev.library.pitt.edu/29229/
title: Knowledge transfer via classification rules using functional mapping for integrative modeling of gene expression data
creator: Ogoe, HA
creator: Visweswaran, S
creator: Lu, X
creator: Gopalakrishnan, V
description: Background: Most 'transcriptomic' data from microarrays are generated from small sample sizes compared to the large number of measured biomarkers, making it very difficult to build accurate and generalizable disease state classification models. Integrating information from different, but related, 'transcriptomic' data may help build better classification models. However, most proposed methods for integrative analysis of 'transcriptomic' data cannot incorporate domain knowledge, which can improve model performance. To this end, we have developed a methodology that leverages transfer rule learning and functional modules, which we call TRL-FM, to capture and abstract domain knowledge in the form of classification rules to facilitate integrative modeling of multiple gene expression data. TRL-FM is an extension of the transfer rule learner (TRL) that we developed previously. The goal of this study was to test our hypothesis that "an integrative model obtained via the TRL-FM approach outperforms traditional models based on single gene expression data sources". Results: To evaluate the feasibility of the TRL-FM framework, we compared the area under the ROC curve (AUC) of models developed with TRL-FM and other traditional methods, using 21 microarray datasets generated from three studies on brain cancer, prostate cancer, and lung disease, respectively. The results show that TRL-FM statistically significantly outperforms TRL as well as traditional models based on single source data. In addition, TRL-FM performed better than other integrative models driven by meta-analysis and cross-platform data merging. Conclusions: The capability of utilizing transferred abstract knowledge derived from source data using feature mapping enables the TRL-FM framework to mimic the human process of learning and adaptation when performing related tasks. The novel TRL-FM methodology for integrative modeling for multiple 'transcriptomic' datasets is able to intelligently incorporate domain knowledge that traditional methods might disregard, to boost predictive power and generalization performance. In this study, TRL-FM's abstraction of knowledge is achieved in the form of functional modules, but the overall framework is generalizable in that different approaches of acquiring abstract knowledge can be integrated into this framework.
date: 2015-07-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29229/1/art%253A10.1186%252Fs12859-015-0643-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29229/7/licence.txt
identifier:   Ogoe, HA and Visweswaran, S and Lu, X and Gopalakrishnan, V  (2015) Knowledge transfer via classification rules using functional mapping for integrative modeling of gene expression data.  BMC Bioinformatics, 16 (1).       
relation: 10.1186/s12859-015-0643-8

relation: http://d-scholarship-dev.library.pitt.edu/28412/
title: Asthma is more severe in older adults
creator: Zein, JG
creator: Dweik, RA
creator: Comhair, SA
creator: Bleecker, ER
creator: Moore, WC
creator: Peters, SP
creator: Busse, WW
creator: Jarjour, NN
creator: Calhoun, WJ
creator: Castro, M
creator: Chung, KF
creator: Fitzpatrick, A
creator: Israel, E
creator: Teague, WG
creator: Wenzel, SE
creator: Love, TE
creator: Gaston, BM
creator: Erzurum, SC
description: © 2015 Zein et al. Background Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration. Methods This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 - 2011 in the Severe Asthma Research Program. Results The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women. Conclusions Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma.
date: 2015-07-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28412/1/journal.pone.0133490.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28412/3/licence.txt
identifier:   Zein, JG and Dweik, RA and Comhair, SA and Bleecker, ER and Moore, WC and Peters, SP and Busse, WW and Jarjour, NN and Calhoun, WJ and Castro, M and Chung, KF and Fitzpatrick, A and Israel, E and Teague, WG and Wenzel, SE and Love, TE and Gaston, BM and Erzurum, SC  (2015) Asthma is more severe in older adults.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0133490

relation: http://d-scholarship-dev.library.pitt.edu/38902/
title: The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence
creator: Lahr, Roni M.
creator: Mack, Seshat M.
creator: Héroux, Annie
creator: Blagden, Sarah P.
creator: Bousquet-Antonelli, Cécile
creator: Deragon, Jean-Marc
creator: Berman, Andrea J.
description: La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5′TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5′ UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5′TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signaling to ribosome biogenesis.
publisher: Oxford University Press
date: 2015-07-22
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/38902/2/The%20La-related%20protein%201-specific%20domain%20repurposes.pdf
identifier:   Lahr, Roni M. and Mack, Seshat M. and Héroux, Annie and Blagden, Sarah P. and Bousquet-Antonelli, Cécile and Deragon, Jean-Marc and Berman, Andrea J.  (2015) The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence.  Nucleic Acids Research, 43 (16).  pp. 8077-8088.  ISSN 0305-1048     
relation: https://academic.oup.com/nar/article/43/16/8077/1076458
relation: 10.1093/nar/gkv748

relation: http://d-scholarship-dev.library.pitt.edu/29230/
title: A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease
creator: Grill, JD
creator: Bateman, RJ
creator: Buckles, V
creator: Oliver, A
creator: Morris, JC
creator: Masters, CL
creator: Klunk, WE
creator: Ringman, JM
description: Introduction: Because of its genetic underpinnings and consistent age of onset within families, autosomal dominant Alzheimer's disease (ADAD) provides a unique opportunity to conduct clinical trials of investigational agents as preventative or symptom-delaying treatments. The design of such trials may be complicated by low rates of genetic testing and disclosure among persons at risk of inheriting disease-causing mutations. Methods: To better understand the attitudes toward genetic testing and clinical trials of persons at risk for ADAD, we surveyed participants in the Dominantly Inherited Alzheimer's Network (DIAN), a multisite longitudinal study of clinical and biomarker outcomes in ADAD that does not require learning genetic status to participate. Results: Eighty participants completed a brief anonymous survey by mail or on-line; 40 % reported knowing if they carried a gene mutation, 15 % did not know but expressed a desire to learn their genetic status, and 45 % did not know and did not desire to know their genetic status. Among participants who knew or wished to know their genetic status, 86 % were interested in participating in a clinical trial. Seventy-two percent of participants who did not wish to learn their genetic status reported that they would change their mind, if learning that they carried a mutation gave them the opportunity to participate in a clinical trial. Nearly all participants responded that they would be interested if an open-label extension were offered. Conclusions: These results suggest that the availability of clinical trials to prevent ADAD can affect persons' desire to undergo genetic testing and that consideration can be given to performing studies in which such testing is required.
date: 2015-07-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29230/1/art%253A10.1186%252Fs13195-015-0135-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29230/7/licence.txt
identifier:   Grill, JD and Bateman, RJ and Buckles, V and Oliver, A and Morris, JC and Masters, CL and Klunk, WE and Ringman, JM  (2015) A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease.  Alzheimer's Research and Therapy, 7 (1).       
relation: 10.1186/s13195-015-0135-0

relation: http://d-scholarship-dev.library.pitt.edu/29231/
title: Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma
creator: Pardee, AD
creator: Yano, H
creator: Weinstein, AM
creator: Ponce, AAK
creator: Ethridge, AD
creator: Normolle, DP
creator: Vujanovic, L
creator: Mizejewski, GJ
creator: Watkins, SC
creator: Butterfield, LH
description: Background: Dendritic cells (DC) are uniquely equipped to capture, process, and present antigens from their environment. The context in which an antigen is acquired by DC helps to dictate the subsequent immune response. Cancer vaccination promotes antitumor immunity by directing an immune response to antigens expressed by tumors. We have tested the tumor-associated antigen alpha-fetoprotein (AFP) as an immunotherapy target. The majority of hepatocellular carcinomas (HCC) upregulate and secrete this oncofetal antigen. Methods: To develop cancer vaccines for HCC capable of promoting potent tumor-specific T cell responses, we tested adenovirally-encoded synthetic AFP, with or without its signal sequence, as well as protein forms of AFP and compared intracellular routing and subsequent antigen-specific CD8+ and CD4+ T cell responses. Results: Surprisingly, the secreted form of antigen was superior for both CD4+ and CD8+ T cell activation. We also examined the mechanism through which AFP protein is endocytosed and trafficked in human DC. We identify the mannose receptor (MR/CD206) as the primary uptake pathway for both normal cord blood-derived AFP (nAFP) and tumor-derived AFP (tAFP) proteins. While in healthy donors, nAFP and tAFP were cross-presented to CD8+ T cells similarly and CD4+ T cell responses were dependent upon MR-mediated uptake. In HCC patient cells, tAFP was more immunogenic, and CD4+ T cell responses were not MR-dependent. Conclusions: Secreted, cytoplasmically retained, and endocytosed forms of AFP utilize unique uptake and processing pathways, resulting in different immunologic responses from the induced antigen-specific CD4+ and CD8+ T cells and between healthy donors and HCC patients. Collectively, these data elucidate pathways of spontaneous and induced anti-tumor immunity in HCC patients to this secreted antigen.
date: 2015-07-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29231/1/art%253A10.1186%252Fs40425-015-0077-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29231/7/licence.txt
identifier:   Pardee, AD and Yano, H and Weinstein, AM and Ponce, AAK and Ethridge, AD and Normolle, DP and Vujanovic, L and Mizejewski, GJ and Watkins, SC and Butterfield, LH  (2015) Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma.  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0077-x

relation: http://d-scholarship-dev.library.pitt.edu/28416/
title: Gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction
creator: Rose, JJ
creator: Voora, D
creator: Cyr, DD
creator: Lucas, JE
creator: Zaas, AK
creator: Woods, CW
creator: Newby, LK
creator: Kraus, WE
creator: Ginsburg, GS
description: Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2%(69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.
date: 2015-07-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28416/1/journal.pone.0132259.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28416/3/licence.txt
identifier:   Rose, JJ and Voora, D and Cyr, DD and Lucas, JE and Zaas, AK and Woods, CW and Newby, LK and Kraus, WE and Ginsburg, GS  (2015) Gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132259

relation: http://d-scholarship-dev.library.pitt.edu/28414/
title: Pro-inflammatory cytokines predict relapse-free survival after one month of interferon-α but not observation in intermediate risk melanoma patients
creator: Tarhini, AA
creator: Lin, Y
creator: Zahoor, H
creator: Shuai, Y
creator: Butterfield, LH
creator: Ringquist, S
creator: Gogas, H
creator: Sander, C
creator: Lee, S
creator: Agarwala, SS
creator: Kirwood, JM
description: Background: E1697 was a phase III trial of adjuvant interferon (IFN)-α2b for one month (Arm B) versus observation (Arm A) in patients with resected melanoma at intermediate risk. We evaluated the levels of candidate serum cytokines, the HLA genotype, polymorphisms of CTLA4 and FOXP3 genes and the development of autoantibodies for their association with relapse free survival (RFS) in Arm A and Arm B among 268 patients with banked biospecimens. Methods: ELISA was used to test 5 autoantibodies. Luminex/One Lambda LABTypeRSSO was used for HLA Genotyping. Selected CTLA4 and FOXP3 Single nucleotide polymorphisms (SNPs) and microsatellites were tested for by polymerase chain reaction (PCR). Sixteen serum cytokines were tested at baseline and one month by Luminex xMAP multiplex technology. Cox Proportional Hazards model was applied and the Wald test was used to test the marginal association of each individual marker and RFS. We used the Lasso approach to select the markers to be included in a multi-marker Cox Proportional Hazards model. The ability of the resulting models to predict one year RFS was evaluated by the time-dependent ROC curve. The leave-one-out method of cross validation (LOOCV) was used to avoid over-fitting of the data. Results: In the multi-marker modeling analysis conducted in Arm B, one month serum IL2Rα, IL- 12p40 and IFNα levels predicted one year RFS with LOOCV AUC = 82%. Among the three markers selected, IL2Rα and IFNα were the most stable (selected in all the cross validation cycles). The risk score (linear combination of the 3 markers) separated the RFS curves of low and high risk groups well (p = 0.05). This model did not hold for Arm A, indicating a differential marker profile in Arm B linked to the intervention (adjuvant therapy). Conclusions: Early on-treatment proinflammatory serum markers (IL2Rα, IL-12p40, IFNα) significantly predict RFS in our cohort of patients treated with adjuvant IFN-α2b and warrant further study.
date: 2015-07-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28414/1/journal.pone.0132745.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28414/3/licence.txt
identifier:   Tarhini, AA and Lin, Y and Zahoor, H and Shuai, Y and Butterfield, LH and Ringquist, S and Gogas, H and Sander, C and Lee, S and Agarwala, SS and Kirwood, JM  (2015) Pro-inflammatory cytokines predict relapse-free survival after one month of interferon-α but not observation in intermediate risk melanoma patients.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132745

relation: http://d-scholarship-dev.library.pitt.edu/29232/
title: Advances in the management of gastrointestinal cancers - An upcoming role of immune checkpoint blockade
creator: Goel, G
creator: Sun, W
description: Gastrointestinal cancers are a group of highly aggressive malignancies, and novel therapeutic strategies with higher clinical efficacy are being actively sought. 'Immunotherapy' is now emerging as one such promising strategy for the treatment of these tumors. This article briefly reviews the recent advances that utilize targeting of immune checkpoint pathways, in the management of gastrointestinal malignancies.
date: 2015-07-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29232/1/art%253A10.1186%252Fs13045-015-0185-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29232/7/licence.txt
identifier:   Goel, G and Sun, W  (2015) Advances in the management of gastrointestinal cancers - An upcoming role of immune checkpoint blockade.  Journal of Hematology and Oncology, 8 (1).       
relation: 10.1186/s13045-015-0185-6

relation: http://d-scholarship-dev.library.pitt.edu/28417/
title: Effects of pesticide mixtures on host-pathogen dynamics of the amphibian chytrid fungus
creator: Buck, JC
creator: Hua, J
creator: Brogan, WR
creator: Dang, TD
creator: Urbina, J
creator: Bendis, RJ
creator: Stoler, AB
creator: Blaustein, AR
creator: Relyea, RA
description: Anthropogenic and natural stressors often interact to affect organisms. Amphibian populations are undergoing unprecedented declines and extinctions with pesticides and emerging infectious diseases implicated as causal factors. Although these factors often cooccur, their effects on amphibians are usually examined in isolation. We hypothesized that exposure of larval and metamorphic amphibians to ecologically relevant concentrations of pesticide mixtures would increase their post-metamorphic susceptibility to the fungus Batra-chochytrium dendrobatidis (Bd), a pathogen that has contributed to amphibian population declines worldwide. We exposed five anuran species (Pacific treefrog, Pseudacris regilla; spring peeper, Pseudacris crucifer; Cascades frog, Rana cascadae; northern leopard frog, Lithobates pipiens; and western toad, Anaxyrus boreas) from three families to mixtures of four common insecticides (chlorpyrifos, carbaryl, permethrin, and endosulfan) or herbicides (glyphosate, acetochlor, atrazine, and 2,4-D) or a control treatment, either as tadpoles or as newly metamorphic individuals (metamorphs). Subsequently, we exposed animals to Bd or a control inoculate after metamorphosis and compared survival and Bd load. Bd exposure significantly increased mortality in Pacific treefrogs, spring peepers, and western toads, but not in Cascades frogs or northern leopard frogs. However, the effects of pesticide exposure on mortality were negligible, regardless of the timing of exposure. Bd load varied considerably across species; Pacific treefrogs, spring peepers, and western toads had the highest loads, whereas Cascades frogs and northern leopard frogs had the lowest loads. The influence of pesticide exposure on Bd load depended on the amphibian species, timing of pesticide exposure, and the particular pesticide treatment. Our results suggest that exposure to realistic pesticide concentrations has minimal effects on Bd-induced mortality, but can alter Bd load. This result could have broad implications for risk assessment of amphibians; the outcome of exposure to multiple stressors may be unpredictable and can differ between species and life stages.
date: 2015-07-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28417/1/journal.pone.0132832.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28417/3/licence.txt
identifier:   Buck, JC and Hua, J and Brogan, WR and Dang, TD and Urbina, J and Bendis, RJ and Stoler, AB and Blaustein, AR and Relyea, RA  (2015) Effects of pesticide mixtures on host-pathogen dynamics of the amphibian chytrid fungus.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132832

relation: http://d-scholarship-dev.library.pitt.edu/28419/
title: Future economics of liver transplantation: A 20-year cost modeling forecast and the prospect of bioengineering autologous liver grafts
creator: Habka, D
creator: Mann, D
creator: Landes, R
creator: Soto-Gutierrez, A
description: During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant- related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this evergrowing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing strategies and economies of scale.
date: 2015-07-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28419/1/journal.pone.0131764.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28419/3/licence.txt
identifier:   Habka, D and Mann, D and Landes, R and Soto-Gutierrez, A  (2015) Future economics of liver transplantation: A 20-year cost modeling forecast and the prospect of bioengineering autologous liver grafts.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0131764

relation: http://d-scholarship-dev.library.pitt.edu/28420/
title: Poly (A) binding protein cytoplasmic 1 is a novel co-regulator of the androgen receptor
creator: Eisermann, K
creator: Dar, JA
creator: Dong, J
creator: Wang, D
creator: Masoodi, KZ
creator: Wang, Z
description: The androgen receptor (AR) is a member of the steroid receptor superfamily that regulates gene expression in a ligand-dependent manner. The NTD of the AR plays a key role in AR transactivation including androgen-independent activation of the AR in castration-resistant prostate cancer (CRPC) cells. We recently reported that amino acids (a.a.) 50-250 of the NTD are capable of modulating AR nucleocytoplasmic trafficking. To further explore the mechanism associated with a.a. 50-250, GFP pull-down assays were performed in C4-2 CRPC cells transfected with GFP tagged a.a. 50-250 of the AR. Mass spectrometry analysis of the pulled down proteins identified poly (A) binding protein cytoplasmic 1 (PABPC1) interaction with this region of the AR. In silicoanalysis of gene expression data revealed PABPC1 up-regulation in prostate cancer tissue specimens and this up-regulation correlates to increased disease recurrence. Co-immunoprecipitation assays confirmed the association of PABPC1 with a.a. 50-250 of the NTD of the AR. Knockdown of PABPC1 decreased nuclear AR protein levels and inhibited androgen activation of the AR target PSA in LNCaP and C4-2 cells. Additionally, knockdown of PABPC1 inhibited transactivation of the PSA promoter by NAR (AR lacking the LBD) and attenuated proliferation of AR-positive prostate cancer cells. These findings suggest that PABPC1 is a novel co-regulator of the AR and may be a potential target for blocking activation of the AR in CRPC.
date: 2015-07-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28420/1/journal.pone.0128495.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28420/3/licence.txt
identifier:   Eisermann, K and Dar, JA and Dong, J and Wang, D and Masoodi, KZ and Wang, Z  (2015) Poly (A) binding protein cytoplasmic 1 is a novel co-regulator of the androgen receptor.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0128495

relation: http://d-scholarship-dev.library.pitt.edu/28418/
title: Predisposition to childhood otitis media and genetic polymorphisms within the toll-like receptor 4 (TLR4) Locus
creator: Hafren, L
creator: Einarsdottir, E
creator: Kentala, E
creator: Hammaren-Malmi, S
creator: Bhutta, MF
creator: MacArthur, CJ
creator: Wilmot, B
creator: Casselbrant, M
creator: Conley, YP
creator: Weeks, DE
creator: Mandel, EM
creator: Vaarala, O
creator: Kallio, A
creator: Melin, M
creator: Nieminen, JK
creator: Leinonen, E
creator: Kere, J
creator: Mattila, PS
description: Background Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFá secretion in myeloid dendritic cells. Conclusions The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.
date: 2015-07-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28418/1/journal.pone.0132551.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28418/3/licence.txt
identifier:   Hafren, L and Einarsdottir, E and Kentala, E and Hammaren-Malmi, S and Bhutta, MF and MacArthur, CJ and Wilmot, B and Casselbrant, M and Conley, YP and Weeks, DE and Mandel, EM and Vaarala, O and Kallio, A and Melin, M and Nieminen, JK and Leinonen, E and Kere, J and Mattila, PS  (2015) Predisposition to childhood otitis media and genetic polymorphisms within the toll-like receptor 4 (TLR4) Locus.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132551

relation: http://d-scholarship-dev.library.pitt.edu/28421/
title: How well do raters agree on the development stage of Caenorhabditis elegans?
creator: Ferguson, AA
creator: Bilonick, RA
creator: Buchanich, JM
creator: Marsh, GM
creator: Fisher, AL
description: The assessment of inter-rater reliability is a topic that is infrequently addressed in Caenorhabditis elegans research, despite the existence of sophisticated statistical methods and the strong interest in the field in obtaining reliable and accurate data. This study applies statistical modeling as a robust means of analyzing the performance of worm researchers measuring the stage of worm development in terms of the two independent factors that comprise "agreement", which are (1) accuracy, representing trueness, a lack of systematic differences, or lack of bias, and (2) precision, representing reliability or the extent to which random differences are small. In our study, multiple raters assessed the same sample of worms to determine the developmental stage of each animal, and we collected data linking each scorer with their assessment for each worm. To describe the agreement of the raters, we developed a structural equation model with latent variables and thresholds, which assumes that all the raters are jointly scoring each worm. This common factor model separately quantifies the two aspects of agreement. The stage-specific thresholds examine accuracy and characterize the relative biases of each rater during the scoring process. The factor loadings for each rater examine the precision and characterizes the random error of the rater. Within our group, we found that the overall agreement was good, while certain adjustments in particular raters would have decreased systematic differences. Hence, the use of developmental stage as an experimental outcome can be both accurate and precise.
date: 2015-07-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28421/1/journal.pone.0132365.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28421/3/licence.txt
identifier:   Ferguson, AA and Bilonick, RA and Buchanich, JM and Marsh, GM and Fisher, AL  (2015) How well do raters agree on the development stage of Caenorhabditis elegans?  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132365

relation: http://d-scholarship-dev.library.pitt.edu/29233/
title: Pan-cancer analysis of TCGA data reveals notable signaling pathways
creator: Neapolitan, R
creator: Horvath, CM
creator: Jiang, X
description: Background: A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. Methods: We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. Results: In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. Conclusions: We obtained 37 notable findings concerning 18 pathways. Some of them appear to be new discoveries. Furthermore, we identified regions on pathways where the aberrant activity might be occurring. We conclude that our results will prove to be valuable to cancer researchers because they provide many opportunities for laboratory and clinical follow-up studies.
date: 2015-07-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29233/1/art%253A10.1186%252Fs12885-015-1484-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29233/7/licence.txt
identifier:   Neapolitan, R and Horvath, CM and Jiang, X  (2015) Pan-cancer analysis of TCGA data reveals notable signaling pathways.  BMC Cancer, 15 (1).       
relation: 10.1186/s12885-015-1484-6

relation: http://d-scholarship-dev.library.pitt.edu/29234/
title: Gene discovery for motile cilia disorders: Mutation spectrum in primary ciliary dyskinesia and discovery of mutations in CCDC151
creator: Onoufriadis, A
creator: Hjeij, R
creator: Watson, CM
creator: Slagle, CE
creator: Klena, NT
creator: Dougherty, GW
creator: Kurkowiak, M
creator: Loges, NT
creator: Diggle, CP
creator: Morante, NF
creator: Gabriel, GC
creator: Lemke, KL
creator: Li, Y
creator: Pennekamp, P
creator: Menchen, T
creator: Marthin, JK
creator: Mans, D
creator: Letteboer, SJ
creator: Werner, C
creator: Burgoyne, T
creator: Westermann, C
creator: Rutman, A
creator: Carr, IM
creator: O'Callaghan, C
creator: Moya, E
creator: Chung, EMK
creator: Sheridan, E
creator: Nielsen, KG
creator: Roepman, R
creator: Burdine, RD
creator: Lo, CW
creator: Omran, H
creator: Mitchison, H
date: 2015-07-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29234/1/art%253A10.1186%252F2046-2530-4-S1-P30.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29234/7/licence.txt
identifier:   Onoufriadis, A and Hjeij, R and Watson, CM and Slagle, CE and Klena, NT and Dougherty, GW and Kurkowiak, M and Loges, NT and Diggle, CP and Morante, NF and Gabriel, GC and Lemke, KL and Li, Y and Pennekamp, P and Menchen, T and Marthin, JK and Mans, D and Letteboer, SJ and Werner, C and Burgoyne, T and Westermann, C and Rutman, A and Carr, IM and O'Callaghan, C and Moya, E and Chung, EMK and Sheridan, E and Nielsen, KG and Roepman, R and Burdine, RD and Lo, CW and Omran, H and Mitchison, H  (2015) Gene discovery for motile cilia disorders: Mutation spectrum in primary ciliary dyskinesia and discovery of mutations in CCDC151.  Cilia (SUPPLE).       
relation: 10.1186/2046-2530-4-S1-P30

relation: http://d-scholarship-dev.library.pitt.edu/32508/
title: A DISTRIBUTED POLYGON RETRIEVAL ALGORITHM USING MAPREDUCE
creator: Guo, Q
creator: Palanisamy, B
creator: Karimi, HA
description: The burst of large-scale spatial terrain data due to the proliferation of data acquisition devices like 3D laser scanners poses challenges to spatial data analysis and computation. Among many spatial analyses and computations, polygon retrieval is a fundamental operation which is often performed under real-time constraints. However, existing sequential algorithms fail to meet this demand for larger sizes of terrain data. Motivated by the MapReduce programming model, a well-adopted large-scale parallel data processing technique, we present a MapReduce-based polygon retrieval algorithm designed with the objective of reducing the IO and CPU loads of spatial data processing. By indexing the data based on a quad-tree approach, a significant amount of unneeded data is filtered in the filtering stage and it reduces the IO overhead. The indexed data also facilitates querying the relationship between the terrain data and query area in shorter time. The results of the experiments performed in our Hadoop cluster demonstrate that our algorithm performs significantly better than the existing distributed algorithms.
date: 2015-07-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32508/1/isprsannals-II-4-W2-51-2015.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32508/4/licence.txt
identifier:   Guo, Q and Palanisamy, B and Karimi, HA  (2015) A DISTRIBUTED POLYGON RETRIEVAL ALGORITHM USING MAPREDUCE.  ISPRS Annals of the Photogrammetry, Remote Sensing and Spatial Information Sciences, 2 (4W2).  51 - 53.  ISSN 2194-9042     
relation: 10.5194/isprsannals-II-4-W2-51-2015

relation: http://d-scholarship-dev.library.pitt.edu/28422/
title: Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli
creator: Field, Brent A.
creator: Buck, Cara L.
creator: McClure, Samuel M.
creator: Nystrom, Leigh E.
creator: Kahneman, Daniel
creator: Cohen, Jonathan D.
contributor: Meck, Warren H
date: 2015-07-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28422/1/journal.pone.0130880.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28422/3/licence.txt
identifier:   Field, Brent A. and Buck, Cara L. and McClure, Samuel M. and Nystrom, Leigh E. and Kahneman, Daniel and Cohen, Jonathan D.  (2015) Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli.  PLOS ONE, 10 (7).  e0130880 - e0130880.      
relation: 10.1371/journal.pone.0130880

relation: http://d-scholarship-dev.library.pitt.edu/29235/
title: Implementation and evaluation of an interprofessional simulation-based education program for undergraduate nursing students in operating room nursing education: A randomized controlled trial
creator: Wang, R
creator: Shi, N
creator: Bai, J
creator: Zheng, Y
creator: Zhao, Y
description: Background: The present study was designed to implement an interprofessional simulation-based education program for nursing students and evaluate the influence of this program on nursing students' attitudes toward interprofessional education and knowledge about operating room nursing. Methods: Nursing students were randomly assigned to either the interprofessional simulation-based education or traditional course group. A before-and-after study of nursing students' attitudes toward the program was conducted using the Readiness for Interprofessional Learning Scale. Responses to an open-ended question were categorized using thematic content analysis. Nursing students' knowledge about operating room nursing was measured. Results: Nursing students from the interprofessional simulation-based education group showed statistically different responses to four of the nineteen questions in the Readiness for Interprofessional Learning Scale, reflecting a more positive attitude toward interprofessional learning. This was also supported by thematic content analysis of the open-ended responses. Furthermore, nursing students in the simulation-based education group had a significant improvement in knowledge about operating room nursing. Conclusions: The integrated course with interprofessional education and simulation provided a positive impact on undergraduate nursing students' perceptions toward interprofessional learning and knowledge about operating room nursing. Our study demonstrated that this course may be a valuable elective option for undergraduate nursing students in operating room nursing education.
date: 2015-07-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29235/1/art%253A10.1186%252Fs12909-015-0400-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29235/7/licence.txt
identifier:   Wang, R and Shi, N and Bai, J and Zheng, Y and Zhao, Y  (2015) Implementation and evaluation of an interprofessional simulation-based education program for undergraduate nursing students in operating room nursing education: A randomized controlled trial.  BMC Medical Education, 15 (1).       
relation: 10.1186/s12909-015-0400-8

relation: http://d-scholarship-dev.library.pitt.edu/25650/
title: Radical Reactions of N -Heterocyclic Carbene Boranes with Organic Nitriles: Cyanation of NHC-Boranes and Reductive Decyanation of Malononitriles
creator: Kawamoto, T
creator: Geib, SJ
creator: Curran, DP
description: The observation that NHC-boryl radicals abstract cyano groups from various organic nitriles has been parlayed into two complementary transformations. In the main group chemistry aspect, reactions of various NHC-boranes with simple organic dinitriles selectively provide stable NHC-boryl mono- or dinitriles, depending on the nitrile source. In the organic synthesis aspect, reaction of malononitriles and related derivatives with readily available 1,3-dimethylimidazol-2-ylidene borane provides reductively decyanated products in good yields.
date: 2015-07-08
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25650/1/licence.txt
identifier:   Kawamoto, T and Geib, SJ and Curran, DP  (2015) Radical Reactions of N -Heterocyclic Carbene Boranes with Organic Nitriles: Cyanation of NHC-Boranes and Reductive Decyanation of Malononitriles.  Journal of the American Chemical Society, 137 (26).  8617 - 8622.  ISSN 0002-7863     
relation: 10.1021/jacs.5b04677

relation: http://d-scholarship-dev.library.pitt.edu/28423/
title: Platelets from asthmatic individuals show less reliance on glycolysis
creator: Xu, W
creator: Cardenes, N
creator: Corey, C
creator: Erzurum, SC
creator: Shiva, S
description: Asthma, a chronic inflammatory airway disease, is typified by high levels of T<inf>H</inf>2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.
date: 2015-07-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28423/1/journal.pone.0132007.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28423/3/licence.txt
identifier:   Xu, W and Cardenes, N and Corey, C and Erzurum, SC and Shiva, S  (2015) Platelets from asthmatic individuals show less reliance on glycolysis.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132007

relation: http://d-scholarship-dev.library.pitt.edu/28424/
title: Comparative magnetic resonance imaging and histopathological correlates in two SOD1 transgenic mouse models of amyotrophic lateral sclerosis
creator: Caron, I
creator: Micotti, E
creator: Paladini, A
creator: Merlino, G
creator: Plebani, L
creator: Forloni, G
creator: Modo, M
creator: Bendotti, C
description: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease due to motoneuron degeneration. Magnetic resonance imaging (MRI) is becoming a promising non-invasive approach to monitor the disease course but a direct correlation with neuropathology is not feasible in human. Therefore in this study we aimed to examine MRI changes in relation to histopathology in two mouse models of ALS (C57BL6/J and 129S2/SvHsd SOD1G93A mice) with different disease onset and progression. A longitudinal in vivo analysis of T2 maps, compared to ex vivo histological changes, was performed on cranial motor nuclei. An increased T2 value was associated with a significant tissue vacuolization that occurred prior to motoneuron loss in the cranial nuclei of C57 SOD1G93A mice. Conversely, in 129Sv SOD1G93A mice, which exhibit a more severe phenotype, MRI detected a milder increase of T2 value, associated with a milder vacuolization. This suggests that alteration within brainstem nuclei is not predictive of a more severe phenotype in the SOD1G93A mouse model. Using an ex vivo paradigm, Diffusion Tensor Imaging was also applied to study white matter spinal cord degeneration. In contrast to degeneration of cranial nuclei, alterations in white matter and axons loss reflected the different disease phenotype of SOD1G93A mice. The correspondence between MRI and histology further highlights the potential of MRI to monitor progressive motoneuron and axonal degeneration non-invasively in vivo. The identification of prognostic markers of the disease nevertheless requires validation in multiple models of ALS to ensure that these are not merely model-specific. Eventually this approach has the potential to lead to the development of robust and validated non-invasive imaging biomarkers in ALS patients, which may help to monitor the efficacy of therapies.
date: 2015-07-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28424/1/journal.pone.0132159.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28424/3/licence.txt
identifier:   Caron, I and Micotti, E and Paladini, A and Merlino, G and Plebani, L and Forloni, G and Modo, M and Bendotti, C  (2015) Comparative magnetic resonance imaging and histopathological correlates in two SOD1 transgenic mouse models of amyotrophic lateral sclerosis.  PLoS ONE, 10 (7).       
relation: 10.1371/journal.pone.0132159

relation: http://d-scholarship-dev.library.pitt.edu/25912/
title: Gertrude H. Lamb, 1918–2015, AHIP, FMLA
creator: Detlefsen, EG
date: 2015-07-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: cc_by_4
identifier: http://d-scholarship-dev.library.pitt.edu/25912/3/mlab-103-03-121.pdf
format: text/plain
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/25912/1/licence.txt
identifier:   Detlefsen, EG  (2015) Gertrude H. Lamb, 1918–2015, AHIP, FMLA.  Journal of the Medical Library Association : JMLA, 103 (3).  121 - 122.      
relation: 10.3163/1536-5050.103.3.003

relation: http://d-scholarship-dev.library.pitt.edu/25649/
title: Revolutionary Mexico, the Sovereign People and the Problem of Men with Guns
creator: Sanchez Lopera, Alejandro
creator: Lund, Joshua
publisher: University of Michigan
date: 2015-07-01
type: Article
type: PeerReviewed
format: text/html
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25649/2/Revolutionary_Mexico%2C_the_Sovereign_People_and_the_Problem_of_Men_with_Guns.html
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25649/4/licence.txt
identifier:   Sanchez Lopera, Alejandro and Lund, Joshua  (2015) Revolutionary Mexico, the Sovereign People and the Problem of Men with Guns.  Política Comun, 7.   ISSN 2007-5227     
relation: http://quod.lib.umich.edu/p/pc/12322227.0007.003?view=text;rgn=main

relation: http://d-scholarship-dev.library.pitt.edu/26081/
title: Toward a Hermeneutics of Data
creator: Acker, A
description: Data science is the systematic process of creating, building, and organizing knowledge with data. A piece of data without context is without meaning, but when data is put into context it becomes meaningful information to people and machines, and it may acquire more contextual information over time. Data's impact on society and studies of data have reached a point for which it is now time for historians of computing to historicize data directly. In fact, computing historians are uniquely positioned to probe the entanglement of networked infrastructures, data, and cultures of computing in the recent past and near future.
date: 2015-07-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26081/1/licence.txt
identifier:   Acker, A  (2015) Toward a Hermeneutics of Data.  IEEE Annals of the History of Computing, 37 (3).  70 - 75.  ISSN 1058-6180     
relation: 10.1109/MAHC.2015.68

relation: http://d-scholarship-dev.library.pitt.edu/26296/
title: Contribución del pensamiento amerindio a una cosmopolítica americana
creator: Duchesne Winter, Juan
description: Extractivism has reached its limits as an irreparable process of sacking nature. Amerindian animistic thought, especially that of the Amazon, postulates ontologies of collective vital activity that offer alternatives to the law of value and its corollaries of productivism and endless accumulation, consubstantial to moderncapitalist civilization.
publisher: Pontificia Universidad Javeriana
date: 2015-07
type: Article
type: PeerReviewed
format: application/pdf
language: es
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26296/1/Cosmopolitica.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26296/4/licence.txt
identifier:   Duchesne Winter, Juan  (2015) Contribución del pensamiento amerindio a una cosmopolítica americana.  Cuadernos de Literatura, XIX (38).  269 - 278.  ISSN 0122-8102     

relation: http://d-scholarship-dev.library.pitt.edu/32618/
title: Hybrid mobile access coordinated wireless sensor networks &amp;#x2014; Design and analysis
creator: Abdelhakim, Mai
creator: Fang, Zhaoxi
creator: Ren, Jian
creator: Li, Tongtong
publisher: IEEE
date: 2015-07
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32618/1/licence.txt
identifier:   Abdelhakim, Mai and Fang, Zhaoxi and Ren, Jian and Li, Tongtong  (2015) Hybrid mobile access coordinated wireless sensor networks &amp;#x2014; Design and analysis.  2015 IEEE China Summit and International Conference on Signal and Information Processing (ChinaSIP).       
relation: 10.1109/chinasip.2015.7230443

relation: http://d-scholarship-dev.library.pitt.edu/33244/
title: Identifying Hidden Talent: How Max Lauffer Brought Jonas Salk to Pittsburgh
creator: Brodt, Zachary
description: This article is primarily concerned with the career of Dr. Max Lauffer and his efforts to hire Jonas Salk as the head of the animal virology laboratory at the University of Pittsburgh.
publisher: The Manuscript Society
date: 2015-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/33244/1/Identifying%20Hidden%20Talent.pdf
identifier:   Brodt, Zachary  (2015) Identifying Hidden Talent: How Max Lauffer Brought Jonas Salk to Pittsburgh.  Manuscripts, 67 (3).  pp. 203-214.  ISSN 0025-262X     

relation: http://d-scholarship-dev.library.pitt.edu/28426/
title: Needs assessment for research use of high- throughput sequencing at a large academic medical center
creator: Geskin, A
creator: Legowski, E
creator: Chakka, A
creator: Chandran, UR
creator: Barmada, MM
creator: LaFramboise, WA
creator: Berg, J
creator: Jacobson, RS
description: Next Generation Sequencing (NGS) methods are driving profound changes in biomedical research, with a growing impact on patient care. Many academic medical centers are evaluating potential models to prepare for the rapid increase in NGS information needs. This study sought to investigate (1) how and where sequencing data is generated and analyzed, (2) research objectives and goals for NGS, (3) workforce capacity and unmet needs, (4) storage capacity and unmet needs, (5) available and anticipated funding resources, and (6) future challenges. As a precursor to informed decision making at our institution, we undertook a systematic needs assessment of investigators using survey methods. We recruited 331 investigators from over 60 departments and divisions at the University of Pittsburgh Schools of Health Sciences and had 140 respondents, or a 42% response rate. Results suggest that both sequencing and analysis bottlenecks currently exist. Significant educational needs were identified, including both investigator-focused needs, such as selection of NGS methods suitable for specific research objectives, and program-focused needs, such as support for training an analytic workforce. The absence of centralized infrastructure was identified as an important institutional gap. Key principles for organizations managing this change were formulated based on the survey responses. This needs assessment provides an in-depth case study which may be useful to other academic medical centers as they identify and plan for future needs.
date: 2015-06-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28426/1/journal.pone.0131166.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28426/3/licence.txt
identifier:   Geskin, A and Legowski, E and Chakka, A and Chandran, UR and Barmada, MM and LaFramboise, WA and Berg, J and Jacobson, RS  (2015) Needs assessment for research use of high- throughput sequencing at a large academic medical center.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0131166

relation: http://d-scholarship-dev.library.pitt.edu/28430/
title: Regulation of pro-apoptotic phosphorylation of Kv2.1 K<sup>+</sup> channels
creator: He, K
creator: McCord, MC
creator: Hartnett, KA
creator: Aizenman, E
description: Caspase activity during apoptosis is inhibited by physiological concentrations of intracellular K+. To enable apoptosis in injured cortical and hippocampal neurons, cellular loss of this cation is facilitated by the insertion of Kv2.1 K+ channels into the plasma membrane via a Zn2+ /CaMKII/SNARE-dependent process. Pro-apoptotic membrane insertion of Kv2.1 requires the dual phosphorylation of the channel by Src and p38 at cytoplasmic N- and C- terminal residues Y124 and S800, respectively. In this study, we investigate if these phosphorylation sites are mutually co-regulated, and whether putative N- and C-terminal interactions, possibly enabled by Kv2.1 intracellular cysteine residues C73 and C710, influence the phosphorylation process itself. Studies were performed with recombinant wild type and mutant Kv2.1 expressed in Chinese hamster ovary (CHO) cells. Using immunoprecipitated Kv2.1 protein and phospho-specific antibodies, we found that an intact Y124 is required for p38 phosphorylation of S800, and, importantly, that Src phosphorylation of Y124 facilitates the action of the p38 at the S800 residue. Moreover, the actions of Src on Kv2.1 are substantially decreased in the non-phosphorylatable S800A channel mutant. We also observed that mutations of either C73 or C710 residues decreased the p38 phosphorylation at S800 without influencing the actions of Src on tyrosine phosphorylation of Kv2.1. Surprisingly, however, apoptotic K+ currents were suppressed only in cells expressing the Kv2.1(C73A) mutant but not in those transfected with Kv2.1(C710A), suggesting a possible structural alteration in the C-terminal mutant that facilitates membrane insertion. These results show that intracellular N-terminal domains critically regulate phosphorylation of the C-terminal of Kv2.1, and vice versa, suggesting possible new avenues for modifying the apoptotic insertion of these channels during neurodegenerative processes.
date: 2015-06-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28430/1/journal.pone.0129498.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28430/3/licence.txt
identifier:   He, K and McCord, MC and Hartnett, KA and Aizenman, E  (2015) Regulation of pro-apoptotic phosphorylation of Kv2.1 K<sup>+</sup> channels.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0129498

relation: http://d-scholarship-dev.library.pitt.edu/28513/
title: A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury
creator: Ziraldo, C
creator: Solovyev, A
creator: Allegretti, A
creator: Krishnan, S
creator: Henzel, MK
creator: Sowa, GA
creator: Brienza, D
creator: An, G
creator: Mi, Q
creator: Vodovotz, Y
description: People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to “better” vs. “worse” outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.
date: 2015-06-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28513/1/journal.pcbi.1004309.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28513/3/licence.txt
identifier:   Ziraldo, C and Solovyev, A and Allegretti, A and Krishnan, S and Henzel, MK and Sowa, GA and Brienza, D and An, G and Mi, Q and Vodovotz, Y  (2015) A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury.  PLoS Computational Biology, 11 (6).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004309

relation: http://d-scholarship-dev.library.pitt.edu/29239/
title: Identification and functional characterization of a novel arginine/ornithine transporter, a member of a cationic amino acid transporter subfamily in the Trypanosoma cruzi genome
creator: Henriques, C
creator: Miller, MP
creator: Catanho, M
creator: De Carvalho, TMU
creator: Krieger, MA
creator: Probst, CM
creator: De Souza, W
creator: Degrave, W
creator: Amara, SG
description: Background: Trypanosoma cruzi, the etiological agent of Chagas disease, is auxotrophic for arginine. It obtains this amino acid from the host through transporters expressed on the plasma membrane and on the membranes of intracellular compartments. A few cationic amino acid transporters have been characterized at the molecular level, such as the novel intracellular arginine/ornithine transporter, TcCAT1.1, a member of the TcCAT subfamily that is composed of four almost identical open reading frames in the T. cruzi genome. Methods: The functional characterization of the TcCAT1.1 isoform was performed in two heterologous expression systems. TcCAT subfamily expression was evaluated by real-time PCR in polysomal RNA fractions, and the cellular localization of TcCAT1.1 fused to EGFP was performed by confocal and immunoelectron microscopy. Results: In the S. cerevisiae expression system, TcCAT1.1 showed high affinity for arginine (Km = 0.085 ± 0.04 mM) and low affinity for ornithine (Km = 1.7 ± 0.2 mM). Xenopus laevis oocytes expressing TcCAT1.1 showed a 7-fold increase in arginine uptake when they were pre-loaded with arginine, indicating that transport is enhanced by substrates on the trans side of the membrane (trans-stimulation). Oocytes that were pre-loaded with [3H]-arginine displayed a 16-fold higher efflux of [3H]-arginine compared with that of the control. Analysis of polysomal RNA fractions demonstrated that the expression of members of the arginine transporter TcCAT subfamily is upregulated under nutritional stress and that this upregulation precedes metacyclogenesis. To investigate the cellular localization of the transporter, EGFP was fused to TcCAT1.1, and fluorescence microscopy and immunocytochemistry revealed the intracellular labeling of vesicles in the anterior region, in a network of tubules and vesicles. Conclusions: TcCAT1.1 is a novel arginine/ornithine transporter, an exchanger expressed in intracellular compartments that is physiologically involved in arginine homeostasis throughout the T. cruzi life cycle. The properties and estimated kinetic parameters of TcCAT1.1 can be extended to other members of the TcCAT subfamily.
date: 2015-06-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29239/1/art%253A10.1186%252Fs13071-015-0950-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29239/7/licence.txt
identifier:   Henriques, C and Miller, MP and Catanho, M and De Carvalho, TMU and Krieger, MA and Probst, CM and De Souza, W and Degrave, W and Amara, SG  (2015) Identification and functional characterization of a novel arginine/ornithine transporter, a member of a cationic amino acid transporter subfamily in the Trypanosoma cruzi genome.  Parasites and Vectors, 8 (1).       
relation: 10.1186/s13071-015-0950-y

relation: http://d-scholarship-dev.library.pitt.edu/28434/
title: Altered structural and functional connectivity in late preterm preadolescence: An anatomic seed-based study of resting state networks related to the posteromedial and lateral parietal cortex
creator: Degnan, AJ
creator: Wisnowski, JL
creator: Choi, S
creator: Ceschin, R
creator: Bhushan, C
creator: Leahy, RM
creator: Corby, P
creator: Schmithorst, VJ
creator: Panigrahy, A
description: Objective: Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Methods: Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Results: Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Conclusion: Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing. Copyright:
date: 2015-06-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28434/1/journal.pone.0130686.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28434/3/licence.txt
identifier:   Degnan, AJ and Wisnowski, JL and Choi, S and Ceschin, R and Bhushan, C and Leahy, RM and Corby, P and Schmithorst, VJ and Panigrahy, A  (2015) Altered structural and functional connectivity in late preterm preadolescence: An anatomic seed-based study of resting state networks related to the posteromedial and lateral parietal cortex.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0130686

relation: http://d-scholarship-dev.library.pitt.edu/28432/
title: Personalized modeling for prediction with decision-path models
creator: Visweswaran, S
creator: Ferreira, A
creator: Ribeiro, GA
creator: Oliveira, AC
creator: Cooper, GF
description: Deriving predictive models in medicine typically relies on a population approach where a single model is developed from a dataset of individuals. In this paper we describe and evaluate a personalized approach in which we construct a new type of decision tree model called decision-path model that takes advantage of the particular features of a given person of interest. We introduce three personalized methods that derive personalized decision-path models. We compared the performance of these methods to that of Classification And Regression Tree (CART) that is a population decision tree to predict seven different outcomes in five medical datasets. Two of the three personalized methods performed statistically significantly better on area under the ROC curve (AUC) and Brier skill score compared to CART. The personalized approach of learning decision path models is a new approach for predictive modeling that can perform better than a population approach.
date: 2015-06-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28432/1/journal.pone.0131022.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28432/3/licence.txt
identifier:   Visweswaran, S and Ferreira, A and Ribeiro, GA and Oliveira, AC and Cooper, GF  (2015) Personalized modeling for prediction with decision-path models.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0131022

relation: http://d-scholarship-dev.library.pitt.edu/28581/
title: A sensitive and specific neural signature for picture-induced negative affect
creator: Chang, LJ
creator: Gianaros, PJ
creator: Manuck, SB
creator: Krishnan, A
creator: Wager, TD
description: Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high–low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion–pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional “emotion-related” regions (e.g., amygdala, insula) or resting-state networks (e.g., “salience,” “default mode”). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes.
date: 2015-06-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28581/1/journal.pbio.1002180.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28581/3/licence.txt
identifier:   Chang, LJ and Gianaros, PJ and Manuck, SB and Krishnan, A and Wager, TD  (2015) A sensitive and specific neural signature for picture-induced negative affect.  PLoS Biology, 13 (6).  1 - 28.  ISSN 1544-9173     
relation: 10.1371/journal.pbio.1002180

relation: http://d-scholarship-dev.library.pitt.edu/28436/
title: Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk
creator: Chornokur, G
creator: Lin, HY
creator: Tyrer, JP
creator: Lawrenson, K
creator: Dennis, J
creator: Amankwah, EK
creator: Qu, X
creator: Tsai, YY
creator: Jim, HSL
creator: Chen, Z
creator: Chen, AY
creator: Permuth-Wey, J
creator: Aben, KKH
creator: Anton-Culver, H
creator: Antonenkova, N
creator: Bruinsma, F
creator: Bandera, EV
creator: Bean, YT
creator: Beckmann, MW
creator: Bisogna, M
creator: Bjorge, L
creator: Bogdanova, N
creator: Brinton, LA
creator: Brooks-Wilson, A
creator: Bunker, CH
creator: Butzow, R
creator: Campbell, IG
creator: Carty, K
creator: Chang-Claude, J
creator: Cook, LS
creator: Cramer, DW
creator: Cunningham, JM
creator: Cybulski, C
creator: Dansonka-Mieszkowska, A
creator: Du Bois, A
creator: Despierre, E
creator: Dicks, E
creator: Doherty, JA
creator: Dörk, T
creator: Dürst, M
creator: Easton, DF
creator: Eccles, DM
creator: Edwards, RP
creator: Ekici, AB
creator: Fasching, PA
creator: Fridley, BL
creator: Gao, YT
creator: Gentry-Maharaj, A
creator: Giles, GG
creator: Glasspool, R
creator: Goodman, MT
creator: Gronwald, J
creator: Harrington, P
creator: Harter, P
creator: Hein, A
creator: Heitz, F
creator: Hildebrandt, MAT
creator: Hillemanns, P
creator: Hogdall, CK
creator: Hogdall, E
creator: Hosono, S
creator: Jakubowska, A
creator: Jensen, A
creator: Ji, BT
creator: Karlan, BY
creator: Kelemen, LE
creator: Kellar, M
creator: Kiemeney, LA
creator: Krakstad, C
creator: Kjaer, SK
creator: Kupryjanczyk, J
creator: Lambrechts, D
creator: Lambrechts, S
creator: Le, ND
creator: Lee, AW
creator: Lele, S
creator: Leminen, A
creator: Lester, J
creator: Levine, DA
creator: Liang, D
creator: Lim, BK
creator: Lissowska, J
creator: Lu, K
creator: Lubinski, J
creator: Lundvall, L
creator: Massuger, LFAG
creator: Matsuo, K
creator: McGuire, V
creator: McLaughlin, JR
creator: McNeish, I
creator: Menon, U
creator: Milne, RL
creator: Modugno, F
creator: Moysich, KB
creator: Ness, RB
creator: Nevanlinna, H
creator: Eilber, U
creator: Odunsi, K
creator: Olson, SH
creator: Orlow, I
description: Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66×10-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
date: 2015-06-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28436/1/journal.pone.0128106.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28436/3/licence.txt
identifier:   Chornokur, G and Lin, HY and Tyrer, JP and Lawrenson, K and Dennis, J and Amankwah, EK and Qu, X and Tsai, YY and Jim, HSL and Chen, Z and Chen, AY and Permuth-Wey, J and Aben, KKH and Anton-Culver, H and Antonenkova, N and Bruinsma, F and Bandera, EV and Bean, YT and Beckmann, MW and Bisogna, M and Bjorge, L and Bogdanova, N and Brinton, LA and Brooks-Wilson, A and Bunker, CH and Butzow, R and Campbell, IG and Carty, K and Chang-Claude, J and Cook, LS and Cramer, DW and Cunningham, JM and Cybulski, C and Dansonka-Mieszkowska, A and Du Bois, A and Despierre, E and Dicks, E and Doherty, JA and Dörk, T and Dürst, M and Easton, DF and Eccles, DM and Edwards, RP and Ekici, AB and Fasching, PA and Fridley, BL and Gao, YT and Gentry-Maharaj, A and Giles, GG and Glasspool, R and Goodman, MT and Gronwald, J and Harrington, P and Harter, P and Hein, A and Heitz, F and Hildebrandt, MAT and Hillemanns, P and Hogdall, CK and Hogdall, E and Hosono, S and Jakubowska, A and Jensen, A and Ji, BT and Karlan, BY and Kelemen, LE and Kellar, M and Kiemeney, LA and Krakstad, C and Kjaer, SK and Kupryjanczyk, J and Lambrechts, D and Lambrechts, S and Le, ND and Lee, AW and Lele, S and Leminen, A and Lester, J and Levine, DA and Liang, D and Lim, BK and Lissowska, J and Lu, K and Lubinski, J and Lundvall, L and Massuger, LFAG and Matsuo, K and McGuire, V and McLaughlin, JR and McNeish, I and Menon, U and Milne, RL and Modugno, F and Moysich, KB and Ness, RB and Nevanlinna, H and Eilber, U and Odunsi, K and Olson, SH and Orlow, I  (2015) Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0128106

relation: http://d-scholarship-dev.library.pitt.edu/29240/
title: Management of septic shock: A protocol-less approach
creator: Cabrera, JL
creator: Pinsky, MR
description: Citation: ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014; 370:1683-93. Background: In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-h protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets including central venous pressure, central venous oxygen saturation, and indirect estimates of cardiac output, than among those receiving usual care. Methods: Objective: The objective was to determine whether these EGDT findings were generalizable and whether all aspects of the EGDT protocol were necessary to achieve those outcomes. Results: A total of 1,351 patients were enrolled, of whom 1,341 were evaluable due to patient/family request: 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and central venous oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0 %), 81 in the protocol-based standard therapy group (18.2 %), and 86 in the usual care group (18.9 %) (relative risk with protocol-based therapy versus usual care, 1.04; 95 % confidence interval, 0.82 to 1.31; P = 0.83; relative risk with protocol-based EGDT versus protocol-based standard therapy, 1.15; 95 % CI, 0.88 to 1.51; P = 0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. Conclusions: In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.
date: 2015-06-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29240/1/art%253A10.1186%252Fs13054-015-0968-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29240/7/licence.txt
identifier:   Cabrera, JL and Pinsky, MR  (2015) Management of septic shock: A protocol-less approach.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0968-8

relation: http://d-scholarship-dev.library.pitt.edu/28435/
title: Naja naja oxiana cobra venom cytotoxins CTI and CTII disrupt mitochondrial membrane integrity: Implications for basic three-fingered cytotoxins
creator: Gasanov, SE
creator: Shrivastava, IH
creator: Israilov, FS
creator: Kim, AA
creator: Rylova, KA
creator: Zhang, B
creator: Dagda, RK
description: Cobra venom cytotoxins are basic three-fingered, amphipathic, non-enzymatic proteins that constitute a major fraction of cobra venom. While cytotoxins cause mitochondrial dysfunction in different cell types, the mechanisms by which cytotoxins bind to mitochondria remain unknown.We analyzed the abilities of CTI and CTII, S-type and P-type cytotoxins from Naja naja oxiana respectively, to associate with isolated mitochondrial fractions or with model membranes that simulate the mitochondrial lipid environment by using a myriad of biophysical techniques. Phosphorus-31 nuclear magnetic resonance (<sup>31</sup>P-NMR) spectroscopy data suggest that both cytotoxins bind to isolated mitochondrial fractions and promote the formation of aberrant non-bilayer structures.We then hypothesized that CTI and CTII bind to cardiolipin (CL) to disrupt mitochondrial membranes. Collectively, <sup>31</sup>P-NMR, electron paramagnetic resonance (EPR), proton NMR (<sup>1</sup>H-NMR), deuterium NMR (<sup>2</sup>H-NMR) spectroscopy, differential scanning calorimetry, and erythrosine phosphorescence assays suggest that CTI and CTII bind to CL to generate non-bilayer structures and promote the permeabilization, dehydration and fusion of large unilamellar phosphatidylcholine (PC) liposomes enriched with CL. On the other hand, CTII but not CTI caused biophysical alterations of large unilamellar PC liposomes enriched with phosphatidylserine (PS). Mechanistically, single molecule docking simulations identified putative CL, PS and PC binding sites in CTI and CTII. While the predicted binding sites for PS and PC share a high number of interactive amino acid residues in CTI and CTII, the CL biding sites in CTII and CTI are more divergent as it contains additional interactive amino acid residues. Overall, our data suggest that cytotoxins physically associate with mitochondrial membranes by binding to CL to disrupt mitochondrial structural integrity.
date: 2015-06-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28435/1/journal.pone.0129248.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28435/3/licence.txt
identifier:   Gasanov, SE and Shrivastava, IH and Israilov, FS and Kim, AA and Rylova, KA and Zhang, B and Dagda, RK  (2015) Naja naja oxiana cobra venom cytotoxins CTI and CTII disrupt mitochondrial membrane integrity: Implications for basic three-fingered cytotoxins.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0129248

relation: http://d-scholarship-dev.library.pitt.edu/25463/
title: Innovators, Esq.: Training the Next Generation of Lawyer Social Entrepreneurs
creator: Dangel, Stephanie
creator: Madison, Michael J
date: 2015-06-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25463/1/Dangel_and_Madison_Innovators%2C_ESQ_IPI_WPS_series.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25463/4/licence.txt
identifier:   Dangel, Stephanie and Madison, Michael J  (2015) Innovators, Esq.: Training the Next Generation of Lawyer Social Entrepreneurs.  University of Missouri-Kansas City Law Review, 83.  967 - 967.      

relation: http://d-scholarship-dev.library.pitt.edu/28439/
title: Moderate exercise mitigates the detrimental effects of aging on tendon stem cells
creator: Zhang, J
creator: Wang, JHC
description: Aging is known to cause tendon degeneration whereas moderate exercise imparts beneficial effects on tendons. Since stem cells play a vital role in maintaining tissue integrity, in this study we aimed to define the effects of aging and moderate exercise on tendon stem/progenitor cells (TSCs) using in vitro and in vivo models. TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. Similarly, 4% mechanical stretching increased the expression of Nanog, another stem cell marker, and the tenocyte-related genes, collagen I and tenomodulin. However, 8% stretching increased expression of the non-tenocyte-related genes, LPL, Sox-9 and Runx-2, while 4% stretching had minimal effects on the expression of these genes. In the in vivo study, moderate treadmill running (MTR) of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration.
date: 2015-06-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28439/1/journal.pone.0130454.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28439/3/licence.txt
identifier:   Zhang, J and Wang, JHC  (2015) Moderate exercise mitigates the detrimental effects of aging on tendon stem cells.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0130454

relation: http://d-scholarship-dev.library.pitt.edu/28467/
title: Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis
creator: Donahoe, M
creator: Valentine, VG
creator: Chien, N
creator: Gibson, KF
creator: Raval, JS
creator: Saul, M
creator: Xue, J
creator: Zhang, Y
creator: Duncan, SR
description: Background: Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods: Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results: Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion: This pilot trial indicates specific treatments that reduce autoantibodies might benefit some severely-ill AE-IPF patients. These findings have potential implications regarding mechanisms of IPF progression, and justify considerations for incremental trials of autoantibody-targeted therapies in AE-IPF patients. Trial Registration: ClinicalTrials.gov NCT01266317.
date: 2015-06-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28467/1/journal.pone.0127771.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28467/3/licence.txt
identifier:   Donahoe, M and Valentine, VG and Chien, N and Gibson, KF and Raval, JS and Saul, M and Xue, J and Zhang, Y and Duncan, SR  (2015) Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0127771

relation: http://d-scholarship-dev.library.pitt.edu/28441/
title: Where you live may make you old: The association between perceived poor neighborhood quality and leukocyte telomere length
creator: Park, M
creator: Verhoeven, JE
creator: Cuijpers, P
creator: Reynolds, CF
creator: Penninx, BWJH
description: Background: Strong evidence supports that living in disadvantaged neighborhoods has direct unfavorable impact on mental and physical health. However, whether it also has direct impact on cellular health is largely unknown. Thus we examined whether neighborhood quality was associated with leukocyte telomere length, an indicator of cellular aging. Methods: In May 2014, we extracted and analyzed baseline data from the Netherlands Study of Depression and Anxiety (NESDA), a large epidemiological study of individuals age between 18-65 years (n=2902). Telomere length was determined using quantitative polymerase chain reaction. Neighborhood quality was assessed using modified measures of perceived neighborhood disorder, fear of crime, and noise. We used multivariable linear regression models to examine association between perceived neighborhood quality and telomere length with comprehensive adjustment for individual and community characteristics related to socioeconomic and demographic status, urbanization level, mental and physical health, and lifestyle. Results: Compared to individuals who reported good neighborhood quality, the mean telomere length of those who reported moderate neighborhood quality was approximately 69 base pair shorter (β =-69.33, 95% CI: -119.49, -19.17, p= 0.007), and that of those who reported poor neighborhood quality were 174 base pair shorter (β =-173.80, 95% CI: -298.80, -49.01, p=0.006). For illustrative purposes, one could extrapolate these outcomes to 8.7 and 11.9 years in chronological age, respectively. Conclusion: We have established an association between perceived neighborhood quality and cellular aging over and above a range of individual attributes. Biological aging processes may be impacted by socioeconomic milieu.
date: 2015-06-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28441/1/journal.pone.0128460.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28441/3/licence.txt
identifier:   Park, M and Verhoeven, JE and Cuijpers, P and Reynolds, CF and Penninx, BWJH  (2015) Where you live may make you old: The association between perceived poor neighborhood quality and leukocyte telomere length.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0128460

relation: http://d-scholarship-dev.library.pitt.edu/29242/
title: Genetic ME-a visualization application for merging and editing pedigrees for genetic studies Medical Informatics and Decision Making
creator: Bui, DK
creator: Jiang, Y
creator: Wei, X
creator: Ortube, MC
creator: Weeks, DE
creator: Conley, YP
creator: Gorin, MB
description: Background: In order to study the genetics of diseases more accurately and effectively, one often collects large families. Different members of a large family may provide differing information about the structure and make-up of their pedigree. Thus, software is needed to facilitate reconciliation of pedigrees collected independently from multiple informants from a single large family to create a unified pedigree that is based on the best composite information available. Findings: Our implementation demonstrates that Genetic ME performs merging in terms of adding, replacing and combining information from two pedigrees. Through a tracking process, all of the changes made to the data set for the individuals can be traced back to their original source material. A new pedigree structure can be easily visualized while reconciling disparate information from multiple pedigrees. Methods: We developed the Genetic Merging & Editing (Genetic ME) program, an open source Java application built on top of CraneFoot and Ghostscript, to support comparing, editing and merging of pedigrees collected from multiple sources in a visually-oriented manner. Conclusions: Genetic ME constitutes an ideal addition to software packages for reconciling pedigree information from multiple sources. Genetic ME provides a friendly graphical user interface, traces the changes made by users, and produces viewable merged pedigree structures able to be further used by other popular analysis programs.
date: 2015-06-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29242/1/art%253A10.1186%252Fs13104-015-1131-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29242/7/licence.txt
identifier:   Bui, DK and Jiang, Y and Wei, X and Ortube, MC and Weeks, DE and Conley, YP and Gorin, MB  (2015) Genetic ME-a visualization application for merging and editing pedigrees for genetic studies Medical Informatics and Decision Making.  BMC Research Notes, 8 (1).       
relation: 10.1186/s13104-015-1131-y

relation: http://d-scholarship-dev.library.pitt.edu/29243/
title: Lhx8 regulates primordial follicle activation and postnatal folliculogenesis
creator: Ren, Y
creator: Suzuki, H
creator: Jagarlamudi, K
creator: Golnoski, K
creator: McGuire, M
creator: Lopes, R
creator: Pachnis, V
creator: Rajkovic, A
description: Background: The early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis. Results: The conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition. Conclusions: Our results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.
date: 2015-06-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29243/1/art%253A10.1186%252Fs12915-015-0151-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29243/7/licence.txt
identifier:   Ren, Y and Suzuki, H and Jagarlamudi, K and Golnoski, K and McGuire, M and Lopes, R and Pachnis, V and Rajkovic, A  (2015) Lhx8 regulates primordial follicle activation and postnatal folliculogenesis.  BMC Biology, 13 (1).       
relation: 10.1186/s12915-015-0151-3

relation: http://d-scholarship-dev.library.pitt.edu/28468/
title: Canonical and noncanonical sites determine NPT2A binding selectivity to NHERF1 PDZ1
creator: Mamonova, T
creator: Zhang, Q
creator: Khajeh, JA
creator: Bu, Z
creator: Bisello, A
creator: Friedman, PA
description: Na<sup>+</sup>/H<sup>+</sup> Exchanger Regulatory Factor-1 (NHERF1) is a scaffolding protein containing 2 PDZ domains that coordinates the assembly and trafficking of transmembrane receptors and ion channels. Most target proteins harboring a C-terminus recognition motif bind more-or-less equivalently to the either PDZ domain, which contain identical core-binding motifs. However some substrates such as the type II sodium-dependent phosphate co-transporter (NPT2A), uniquely bind only one PDZ domain. We sought to define the structural determinants responsible for the specificity of interaction between NHERF1 PDZ domains and NPT2A. By performing all-atom/explicit-solvent molecular dynamics (MD) simulations in combination with biological mutagenesis, fluorescent polarization (FP) binding assays, and isothermal titration calorimetry (ITC), we found that in addition to canonical interactions of residues at 0 and -2 positions, Arg at the -1 position of NPT2A plays a critical role in association with Glu43 and His27 of PDZ1 that are absent in PDZ2. Experimentally introduced mutation in PDZ1 (Glu43Asp and His27Asn) decreased binding to NPT2A. Conversely, introduction of Asp183Glu and Asn167His mutations in PDZ2 promoted the formation of favorable interactions yielding micromolar K<inf>D</inf>s. The results describe novel determinants within both the PDZ domain and outside the canonical PDZ-recognition motif that are responsible for discrimination of NPT2A between two PDZ domains. The results challenge general paradigms for PDZ recognition and suggest new targets for drug development.
date: 2015-06-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28468/1/journal.pone.0129554.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28468/3/licence.txt
identifier:   Mamonova, T and Zhang, Q and Khajeh, JA and Bu, Z and Bisello, A and Friedman, PA  (2015) Canonical and noncanonical sites determine NPT2A binding selectivity to NHERF1 PDZ1.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0129554

relation: http://d-scholarship-dev.library.pitt.edu/28514/
title: The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap
creator: Brown, JW
creator: Bullitt, E
creator: Sriswasdi, S
creator: Harper, S
creator: Speicher, DW
creator: McKnight, CJ
description: © 2015 Brown et al. The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin’s physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin’s quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.
date: 2015-06-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28514/1/journal.pcbi.1004302.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28514/3/licence.txt
identifier:   Brown, JW and Bullitt, E and Sriswasdi, S and Harper, S and Speicher, DW and McKnight, CJ  (2015) The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap.  PLoS Computational Biology, 11 (6).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004302

relation: http://d-scholarship-dev.library.pitt.edu/29245/
title: SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp
creator: Hwang, BJ
creator: Jin, J
creator: Gao, Y
creator: Shi, G
creator: Madabushi, A
creator: Yan, A
creator: Guan, X
creator: Zalzman, M
creator: Nakajima, S
creator: Lan, L
creator: Lu, AL
description: Background: SIRT6, a member of the NAD+-dependent histone/protein deacetylase family, regulates genomic stability, metabolism, and lifespan. MYH glycosylase and APE1 are two base excision repair (BER) enzymes involved in mutation avoidance from oxidative DNA damage. Rad9-Rad1-Hus1 (9-1-1) checkpoint clamp promotes cell cycle checkpoint signaling and DNA repair. BER is coordinated with the checkpoint machinery and requires chromatin remodeling for efficient repair. SIRT6 is involved in DNA double-strand break repair and has been implicated in BER. Here we investigate the direct physical and functional interactions between SIRT6 and BER enzymes. Results: We show that SIRT6 interacts with and stimulates MYH glycosylase and APE1. In addition, SIRT6 interacts with the 9-1-1 checkpoint clamp. These interactions are enhanced following oxidative stress. The interdomain connector of MYH is important for interactions with SIRT6, APE1, and 9-1-1. Mutagenesis studies indicate that SIRT6, APE1, and Hus1 bind overlapping but different sequence motifs on MYH. However, there is no competition of APE1, Hus1, or SIRT6 binding to MYH. Rather, one MYH partner enhances the association of the other two partners to MYH. Moreover, APE1 and Hus1 act together to stabilize the MYH/SIRT6 complex. Within human cells, MYH and SIRT6 are efficiently recruited to confined oxidative DNA damage sites within transcriptionally active chromatin, but not within repressive chromatin. In addition, Myh foci induced by oxidative stress and Sirt6 depletion are frequently localized on mouse telomeres. Conclusions: Although SIRT6, APE1, and 9-1-1 bind to the interdomain connector of MYH, they do not compete for MYH association. Our findings indicate that SIRT6 forms a complex with MYH, APE1, and 9-1-1 to maintain genomic and telomeric integrity in mammalian cells.
date: 2015-06-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29245/1/art%253A10.1186%252Fs12867-015-0041-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29245/7/licence.txt
identifier:   Hwang, BJ and Jin, J and Gao, Y and Shi, G and Madabushi, A and Yan, A and Guan, X and Zalzman, M and Nakajima, S and Lan, L and Lu, AL  (2015) SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp.  BMC Molecular Biology, 16 (1).       
relation: 10.1186/s12867-015-0041-9

relation: http://d-scholarship-dev.library.pitt.edu/31016/
title: Walking Dead and Vengeful Spirits
creator: Sulosky Weaver, CL
description: For the ancient Greeks, the dead were subjects of both fear and supplication. Necrophobia, or the fear of the dead, is a concept that has been present in Greek culture since the Neolithic period. At the heart of this phobia is the belief that corpses are able to reanimate and exist in a state that is neither living nor dead, but rather ‘undead.’ These liminal figures are deemed to be dangerous because it is understood that they leave their graves at night for the explicit purpose of harming the living. As a means of protection, the alleged undead were pinned in their graves or ritually ‘killed.’ Paradoxically, the Greeks also practiced necromancy, the purposeful invocation of the dead. The dead were typically entreated by means of binding spells inscribed on thin sheets of lead. These spells, called katadesmoi, were deposited in graves during nighttime ceremonies. Often petitioners sought to redress a wrong that had been committed, such as avenging a murder or returning a stolen inheritance, but katadesmoi were also used to gain an advantage in love or business. This article presents archaeological evidence of necrophobia and necromancy dating to the 5th through 3rd centuries BCE from the Greek site of Kamarina in southeastern Sicily. Details of the burial contexts will be given, possible explanations examined and parallel cases discussed, ultimately placing these macabre customs within the wider framework of Greek mortuary practices.
publisher: Popular Archaeology
date: 2015-06-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/31016/1/Walking%20Dead%20and%20Vengeful%20Spirits.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/31016/6/licence.txt
identifier:   Sulosky Weaver, CL  (2015) Walking Dead and Vengeful Spirits.  Walking Dead and Vengeful Spirits, 19.       
relation: http://popular-archaeology.com/issue/summer-2015/article/walking-dead-and-vengeful-spirits

relation: http://d-scholarship-dev.library.pitt.edu/29246/
title: Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: A case report
creator: Frech, TM
creator: Revelo, MP
creator: Ryan, JJ
creator: Shah, AA
creator: Gordon, J
creator: Domsic, R
creator: Hant, F
creator: Assassi, S
creator: Shanmugam, VK
creator: Hinchcliff, M
creator: Steen, V
creator: Khanna, D
creator: Bernstein, EJ
creator: Cox, J
creator: Luem, N
creator: Drakos, S
description: Introduction: Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear. Case presentation: A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis. Conclusion: In this case report, we present the finding of cardiac tissue metabolomics, which may indicate a problem with vasodilation as a contributor to cardiac death in diffuse systemic sclerosis. The use of autopsy and tissue metabolomics in rare disease may help clarify disease pathogenesis.
date: 2015-06-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29246/1/art%253A10.1186%252Fs13256-015-0587-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29246/7/licence.txt
identifier:   Frech, TM and Revelo, MP and Ryan, JJ and Shah, AA and Gordon, J and Domsic, R and Hant, F and Assassi, S and Shanmugam, VK and Hinchcliff, M and Steen, V and Khanna, D and Bernstein, EJ and Cox, J and Luem, N and Drakos, S  (2015) Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: A case report.  Journal of Medical Case Reports, 9 (1).       
relation: 10.1186/s13256-015-0587-7

relation: http://d-scholarship-dev.library.pitt.edu/29258/
title: Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation
creator: Dueck, H
creator: Khaladkar, M
creator: Kim, TK
creator: Spaethling, JM
creator: Francis, C
creator: Suresh, S
creator: Fisher, SA
creator: Seale, P
creator: Beck, SG
creator: Bartfai, T
creator: Kuhn, B
creator: Eberwine, J
creator: Kim, J
description: Background: Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question. Results: We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved. Conclusions: Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.
date: 2015-06-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29258/1/art%253A10.1186%252Fs13059-015-0683-4.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29258/7/licence.txt
identifier:   Dueck, H and Khaladkar, M and Kim, TK and Spaethling, JM and Francis, C and Suresh, S and Fisher, SA and Seale, P and Beck, SG and Bartfai, T and Kuhn, B and Eberwine, J and Kim, J  (2015) Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.  Genome Biology, 16 (1).   ISSN 1474-7596     
relation: 10.1186/s13059-015-0683-4

relation: http://d-scholarship-dev.library.pitt.edu/28469/
title: Dialyzer reuse and outcomes of high flux dialysis
creator: Argyropoulos, C
creator: Roumelioti, ME
creator: Sattar, A
creator: Kellum, JA
creator: Weissfeld, L
creator: Unruh, ML
description: Background: The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers. Methods: Proportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between β2-microglobulin (β2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO. Findings: In HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48-0.92, p = 0.015), 0.64 (95%CI: 0.44-0.95, p = 0.03), 0.61 (95%CI: 0.41-0.90, p = 0.012), 0.53 (95%CI: 0.28-1.02, p = 0.057) relative to minimally reused LF ones for all cause, cardiovascular, cardiac and infectious mortality respectively. These relationships reversed for extensively reused membranes (p for interaction between reuse and flux < 0.001, p = 0.005) for death from all cause and cardiovascular causes, while similar trends were noted for cardiac and infectious mortality (p of interaction between reuse and flux of 0.10 and 0.08 respectively). Reduction of β2M explained only 1/3 of the effect of minimally reused HF dialyzers on all cause mortality, while non-β2M related factors explained the apparent attenuation of the benefit with more extensively reused dialyzers. Meta-regression of HEMO and MPO estimated an adjusted HR of 0.63 (95% CI: 0.51-0.78) for non-reused HF dialyzers compared with non-reused LF membranes. Conclusions: This secondary analysis and synthesis of two large hemodialysis trials supports the widespread use of HF dialyzers in clinical hemodialysis over the last decade. A mechanistic understanding of the effects of HF dialysis and the reuse process on dialyzers may suggest novel biomarkers for uremic toxicity and may accelerate membrane technology innovations that will improve patient outcomes.
date: 2015-06-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28469/1/journal.pone.0129575.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28469/3/licence.txt
identifier:   Argyropoulos, C and Roumelioti, ME and Sattar, A and Kellum, JA and Weissfeld, L and Unruh, ML  (2015) Dialyzer reuse and outcomes of high flux dialysis.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0129575

relation: http://d-scholarship-dev.library.pitt.edu/29259/
title: Developing an animal model of Dupuytren's disease by orthotopic transplantation of human fibroblasts into athymic rat
creator: Satish, L
creator: Palmer, B
creator: Liu, F
creator: Papatheodorou, L
creator: Rigatti, L
creator: Baratz, ME
creator: Kathju, S
description: Background: Dupuytren's disease (DD) is a slow, progressive fibroproliferative disorder affecting the palms of the hands. The disease is characterized by the formation of collagen rich- cords which gradually shorten by the action of myofibroblasts resulting in finger contractures. It is a disease that is confined to humans, and a major limiting factor in investigating this disorder has been the lack of a faithful animal model that can recapitulate its distinct biology. The aim of this study was to develop such a model by determining if Dupuytren's disease (DD)- and control carpal tunnel (CT)-derived fibroblasts could survive in the forepaw of the nude rats and continue to exhibit the distinct characteristics they display in in vitro cultures. Methods: 1×107 fluorescently labeled DD- and CT-derived fibroblasts were transplanted into the left and right forepaws of nude rats respectively. Cells were tracked at regular intervals for a period of two months by quantifying emitted fluorescent signal using an IVIS imaging system. After a period of 62 days rat forepaw connective tissues were harvested for histology and total RNA was isolated. Human-specific probes were used to perform real time RT-PCR assays to examine the expression patterns of gene products associated with fibrosis in DD. Rat forepaw skin was also harvested to serve as an internal control. Results: Both CT- and DD-derived fibroblasts survived for a period of 62 days, but DD-derived cells showed a significantly greater level of persistent fluorescent signal at the end of this time than did CT-derived cells. mRNA expression levels of α-smooth muscle actin (α-SMA), type I- and type III- collagens were all significantly elevated in the forepaw receiving DD cord-derived fibroblasts in comparison to CT-derived fibroblasts. Masson's trichrome stain confirmed increased collagen deposition in the forepaw that was injected with DD cord-derived fibroblasts. Conclusions: For the first time we describe an animal model for Dupuytren's disease at the orthotopic anatomical location. We further show that gene expression differences between control (CT) and diseased (DD) derived fibroblasts persist when these cells are transplanted to the forepaw of the nude rat. These preliminary findings indicate that, with further refinements, this animal model holds promise as a baseline for investigating novel therapeutic regimens to determine an effective strategy in treating DD.
date: 2015-06-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29259/1/art%253A10.1186%252Fs12891-015-0597-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29259/7/licence.txt
identifier:   Satish, L and Palmer, B and Liu, F and Papatheodorou, L and Rigatti, L and Baratz, ME and Kathju, S  (2015) Developing an animal model of Dupuytren's disease by orthotopic transplantation of human fibroblasts into athymic rat.  BMC Musculoskeletal Disorders, 16 (1).       
relation: 10.1186/s12891-015-0597-z

relation: http://d-scholarship-dev.library.pitt.edu/25476/
title: Tracking employment shocks using mobile phone data
creator: Toole, JL
creator: Lin, YR
creator: Muehlegger, E
creator: Shoag, D
creator: González, MC
creator: Lazer, D
description: Can data from mobile phones be used to observe economic shocks and their consequences at multiple scales? Here we present novel methods to detect mass layoffs, identify individuals affected by them and predict changes in aggregate unemployment rates using call detail records (CDRs) from mobile phones. Using the closure of a large manufacturing plant as a case study, we first describe a structural break model to correctly detect the date of a mass layoff and estimate its size. We then use a Bayesian classification model to identify affected individuals by observing changes in calling behaviour following the plant's closure. For these affected individuals, we observe significant declines in social behaviour and mobility following job loss. Using the features identified at the micro level, we show that the same changes in these calling behaviours, aggregated at the regional level, can improve forecasts of macro unemployment rates. These methods and results highlight promise of new data resources to measure microeconomic behaviour and improve estimates of critical economic indicators.
date: 2015-06-06
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25476/1/licence.txt
identifier:   Toole, JL and Lin, YR and Muehlegger, E and Shoag, D and González, MC and Lazer, D  (2015) Tracking employment shocks using mobile phone data.  Journal of the Royal Society Interface, 12 (107).   ISSN 1742-5689     
relation: 10.1098/rsif.2015.0185

relation: http://d-scholarship-dev.library.pitt.edu/29267/
title: Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study
creator: Messinger, DS
creator: Young, GS
creator: Webb, SJ
creator: Ozonoff, S
creator: Bryson, SE
creator: Carter, A
creator: Carver, L
creator: Charman, T
creator: Chawarska, K
creator: Curtin, S
creator: Dobkins, K
creator: Hertz-Picciotto, I
creator: Hutman, T
creator: Iverson, JM
creator: Landa, R
creator: Nelson, CA
creator: Stone, WL
creator: Tager-Flusberg, H
creator: Zwaigenbaum, L
description: Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.
date: 2015-06-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29267/1/art%253A10.1186%252Fs13229-015-0027-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29267/7/licence.txt
identifier:   Messinger, DS and Young, GS and Webb, SJ and Ozonoff, S and Bryson, SE and Carter, A and Carver, L and Charman, T and Chawarska, K and Curtin, S and Dobkins, K and Hertz-Picciotto, I and Hutman, T and Iverson, JM and Landa, R and Nelson, CA and Stone, WL and Tager-Flusberg, H and Zwaigenbaum, L  (2015) Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study.  Molecular Autism, 6 (1).       
relation: 10.1186/s13229-015-0027-y

relation: http://d-scholarship-dev.library.pitt.edu/29263/
title: Molecular drivers of lobular carcinoma in situ
creator: Logan, GJ
creator: Dabbs, DJ
creator: Lucas, PC
creator: Jankowitz, RC
creator: Brown, DD
creator: Clark, BZ
creator: Oesterreich, S
creator: McAuliffe, PF
description: Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. This review focuses on the molecular drivers of lobular carcinoma, a more complete understanding of which may give perspective on which LCIS lesions progress, and which will not, thus having immense clinical implications.
date: 2015-06-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29263/1/art%253A10.1186%252Fs13058-015-0580-5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29263/7/licence.txt
identifier:   Logan, GJ and Dabbs, DJ and Lucas, PC and Jankowitz, RC and Brown, DD and Clark, BZ and Oesterreich, S and McAuliffe, PF  (2015) Molecular drivers of lobular carcinoma in situ.  Breast Cancer Research, 17 (1).   ISSN 1465-5411     
relation: 10.1186/s13058-015-0580-5

relation: http://d-scholarship-dev.library.pitt.edu/28586/
title: What factors might have led to the emergence of ebola in West Africa?
creator: Alexander, KA
creator: Sanderson, CE
creator: Marathe, M
creator: Lewis, BL
creator: Rivers, CM
creator: Shaman, J
creator: Drake, JM
creator: Lofgren, E
creator: Dato, VM
creator: Eisenberg, MC
creator: Eubank, S
description: An Ebola outbreak of unprecedented scope emerged in West Africa in December 2013 and presently continues unabated in the countries of Guinea, Sierra Leone, and Liberia. Ebola is not new to Africa, and outbreaks have been confirmed as far back as 1976. The current West African Ebola outbreak is the largest ever recorded and differs dramatically from prior outbreaks in its duration, number of people affected, and geographic extent. The emergence of this deadly disease in West Africa invites many questions, foremost among these: why now, and why in West Africa? Here, we review the sociological, ecological, and environmental drivers that might have influenced the emergence of Ebola in this region of Africa and its spread throughout the region. Containment of the West African Ebola outbreak is the most pressing, immediate need. A comprehensive assessment of the drivers of Ebola emergence and sustained human-to-human transmission is also needed in order to prepare other countries for importation or emergence of this disease. Such assessment includes identification of country-level protocols and interagency policies for outbreak detection and rapid response, increased understanding of cultural and traditional risk factors within and between nations, delivery of culturally embedded public health education, and regional coordination and collaboration, particularly with governments and health ministries throughout Africa. Public health education is also urgently needed in countries outside of Africa in order to ensure that risk is properly understood and public concerns do not escalate unnecessarily. To prevent future outbreaks, coordinated, multiscale, early warning systems should be developed that make full use of these integrated assessments, partner with local communities in high-risk areas, and provide clearly defined response recommendations specific to the needs of each community.
date: 2015-06-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28586/1/journal.pntd.0003652.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28586/3/licence.txt
identifier:   Alexander, KA and Sanderson, CE and Marathe, M and Lewis, BL and Rivers, CM and Shaman, J and Drake, JM and Lofgren, E and Dato, VM and Eisenberg, MC and Eubank, S  (2015) What factors might have led to the emergence of ebola in West Africa?  PLoS Neglected Tropical Diseases, 9 (6).   ISSN 1935-2727     
relation: 10.1371/journal.pntd.0003652

relation: http://d-scholarship-dev.library.pitt.edu/28470/
title: Perinatal outcomes and unconventional natural gas operations in Southwest Pennsylvania
creator: Stacy, SL
creator: Brink, LAL
creator: Larkin, JC
creator: Sadovsky, Y
creator: Goldstein, BD
creator: Pitt, BR
creator: Talbott, EO
description: Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007-2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10-1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.
date: 2015-06-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28470/1/journal.pone.0126425.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28470/3/licence.txt
identifier:   Stacy, SL and Brink, LAL and Larkin, JC and Sadovsky, Y and Goldstein, BD and Pitt, BR and Talbott, EO  (2015) Perinatal outcomes and unconventional natural gas operations in Southwest Pennsylvania.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0126425

relation: http://d-scholarship-dev.library.pitt.edu/25509/
title: The Spine concept for improving network availability
creator: Alashaikh, A
creator: Gomes, T
creator: Tipper, D
description: Telecommunications networks need to guarantee that all node pairs involved in critical service communications are highly available. Here we adopt a novel approach to the problem of how to provide high levels of availability in an efficient manner. The basic idea is to embed at the physical layer a high availability set of links and nodes (termed the spine) in the network topology to support protection and routing in providing end-to-end availability. We first explore the spine concept through simple topologies illustrating the potential benefits of the approach in improving the overall network availability and the capability to support quality of resilience classes. Then, we study how the structural properties of a network topology can be used to determine heuristics to select a suitable spine and compare this with the case where all network components have the same availability. This is followed by a numerical based study comparing the heuristics with all possible spanning tree based spines for sample topologies. Our results demonstrate how to best design a physical network to support protection methods in achieving high levels of availability efficiently.
date: 2015-06-03
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25509/1/licence.txt
identifier:   Alashaikh, A and Gomes, T and Tipper, D  (2015) The Spine concept for improving network availability.  Computer Networks, 82.  4 - 19.  ISSN 1389-1286     
relation: 10.1016/j.comnet.2015.02.020

relation: http://d-scholarship-dev.library.pitt.edu/28471/
title: Depression and anxiety disorders among hospitalized women with breast cancer
creator: Vin-Raviv, N
creator: Akinyemiju, TF
creator: Galea, S
creator: Bovbjerg, DH
description: Purpose: To document the prevalence of depression and anxiety disorders, and their associations with mortality among hospitalized breast cancer patients. Methods: We examined the associations between breast cancer diagnosis and the diagnoses of anxiety or depression among 4,164 hospitalized breast cancer cases matched with 4,164 non-breast cancer controls using 2006-2009 inpatient data obtained from the Nationwide Inpatient Sample database. Conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) for the associations between breast cancer diagnosis and diagnoses of anxiety or depression. We also used binary logistic regression models to examine the association between diagnoses of depression or anxiety, and in-hospital mortality among breast cancer patients. Results: We observed that breast cancer cases were less likely to have a diagnosis of depression (OR=0.63, 95% CI: 0.52-0.77), and less likely to have a diagnosis of anxiety (OR=0.68, 95% CI: 0.52-0.90) compared with controls. This association remained after controlling for race/ethnicity, residential income, insurance and residential region. Breast cancer patients with a depression diagnosis also had lower mortality (OR=0.69, 95% CI: 0.52-0.89) compared with those without a depression diagnosis, but there was no significant difference in mortality among those with and without anxiety diagnoses. Conclusion: Diagnoses of depression and anxiety in breast cancer patients were less prevalent than expected based on our analysis of hospitalized breast cancer patients and matched nonbreast cancer controls identified in the NIS dataset using ICD-9 diagnostic codes. Results suggest that under-diagnosis of mental health problems may be common among hospitalized women with a primary diagnosis of breast cancer. Future work may fruitfully explore reasons for, and consequences of, inappropriate identification of the mental health needs of breast cancer patients.
date: 2015-06-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28471/1/journal.pone.0129169.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28471/3/licence.txt
identifier:   Vin-Raviv, N and Akinyemiju, TF and Galea, S and Bovbjerg, DH  (2015) Depression and anxiety disorders among hospitalized women with breast cancer.  PLoS ONE, 10 (6).       
relation: 10.1371/journal.pone.0129169

relation: http://d-scholarship-dev.library.pitt.edu/32680/
title: Dopaminergic modulation of lateral amygdala neuronal activity: Differential d1 and d2 receptor effects on thalamic and cortical afferent inputs
creator: Chang, CH
creator: Grace, AA
description: Background: In auditory fear conditioning, the lateral nucleus of the amygdala (LA) integrates a conditioned stimulus (CS) from the auditory thalamus (MGN) and the auditory association cortex (Te3) with an aversive unconditioned stimulus. The thalamic input provides a basic version of the CS, while the cortical input provides a processed representation of the stimulus. Dopamine (DA) is released in the LA under heightened arousal during the presentation of the CS. Methods: In this study we examined how D1 or D2 receptor activation affects LA afferent-driven neuronal firing using in vivo extracellular single-unit recordings with local micro-iontophoretic drug application in anesthetized rats. LA neurons that were responsive (~50%) to electrical stimulation in either the MGN or the Te3 were tested by iontophoresis of either the D1 agonist, SKF38393, or the D2 agonist, quinpirole. Results: We found that most of the LA projection neurons exhibited either facilitatory or attenuating effects (changes in evoked probability 15% relative to baseline) on afferent input by activation of D1 or D2 receptors. In general, it required significantly higher stimulation current to evoke ~50% baseline responses to the cortical input. Activation of the D1 receptor showed no difference in modulation between the thalamic or cortical pathways. On the other hand, activation of the D2 receptor had a stronger inhibitory modulation of the cortical pathway, but a stronger excitatory modulation of the thalamic pathway. Conclusions: Our results suggest that there is a shift in balance favoring the thalamic pathway in response to DA acting via the D2 receptor..
date: 2015-06-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32680/1/pyv015.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32680/7/licence.txt
identifier:   Chang, CH and Grace, AA  (2015) Dopaminergic modulation of lateral amygdala neuronal activity: Differential d1 and d2 receptor effects on thalamic and cortical afferent inputs.  International Journal of Neuropsychopharmacology, 18 (8).  1 - 8.  ISSN 1461-1457     
relation: 10.1093/ijnp/pyv015

relation: http://d-scholarship-dev.library.pitt.edu/25425/
title: From cyberbullying to well-being: A narrative-based participatory approach to values-oriented design for social media
creator: Bowler, L
creator: Knobel, C
creator: Mattern, E
description: This study looks at mean and cruel online behavior through the lens of design, with the goal of developing positive technologies for youth. Narrative inquiry was used as a research method, allowing two focus groups - one composed of teens and the other of undergraduate students - to map out 4 cyberbullying stories. Each cyberbullying story revealed 2 subplots - the story that "is" (as perceived by these participants) and the story that "could be" (if the participants' design recommendations were embedded in social media). The study resulted in a user-generated framework for designing affordances on social media sites to counter acts of cyberbullying. Seven emergent design themes are evident in the participants' cyberbullying narratives: design for hesitation, design for consequence, design for empathy, design for personal empowerment, design for fear, design for attention, and design for control and suppression. We conclude with a typological analysis of the values present in the participants' design recommendations, applying Cheng and Fleischman's values framework (2010).
date: 2015-06-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25425/1/licence.txt
identifier:   Bowler, L and Knobel, C and Mattern, E  (2015) From cyberbullying to well-being: A narrative-based participatory approach to values-oriented design for social media.  Journal of the Association for Information Science and Technology, 66 (6).  1274 - 1293.  ISSN 2330-1635     
relation: 10.1002/asi.23270

relation: http://d-scholarship-dev.library.pitt.edu/25412/
title: Real-time sidewalk slope calculation through integration of GPS trajectory and image data to assist people with disabilities in navigation
creator: Lu, Y
creator: Karimi, HA
description: People with disabilities face many obstacles in everyday outdoor travels. One of the most notable obstacles is steep slope on sidewalk segments. Current navigation systems/services do not all support map databases with slope attributes and cannot calculate sidewalk slope in real time. In this paper, we present a technique for calculating slopes of sidewalk segments by image data and predict the most suitable route for each individual user through integration with GPS trajectory. In our technique we make use of GPS trajectory data, to identify the sidewalk segment on which the traveler will most probably pass, and images of the identified sidewalk segment. Through edge detection techniques we detect edges of objects, such as buildings, billboards, and walls, in the background. Slope of the segment is then calculated by comparing its line representation in the map with the detected edges. Our experiment result indicates effective calculation of sidewalk slopes.
date: 2015-06-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25412/1/ijgi-04-00741-v2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25412/4/licence.txt
identifier:   Lu, Y and Karimi, HA  (2015) Real-time sidewalk slope calculation through integration of GPS trajectory and image data to assist people with disabilities in navigation.  ISPRS International Journal of Geo-Information, 4 (2).  741 - 753.      
relation: 10.3390/ijgi4020741

relation: http://d-scholarship-dev.library.pitt.edu/29268/
title: Two-stage therapeutic utility of ectopically formed bone tissue in skeletal muscle induced by adeno-associated virus containing bone morphogenetic protein-4 gene
creator: Tian, K
creator: Qi, M
creator: Wang, L
creator: Li, Z
creator: Xu, J
creator: Li, Y
creator: Liu, G
creator: Wang, B
creator: Huard, J
creator: Li, G
description: Background: The major disadvantage of using a stem cell-based bone morphogenetic protein-4 (BMP4) gene therapy for skull defect is the overgrowth of generated bone tissue in situ. In the present study, to overcome bony overgrowth of stem cell based-gene therapy, a new strategy of two-stage bone tissue engineering by an adeno-associated virus containing BMP4 gene (AAV-BMP4) gene therapy was used. Methods: AAV-BMP4 was purposely implanted in the skeletal muscle of mice to generate ectopic bone tissues during the first stage. Next, the newly formed ectopic bone tissues were harvested and then transplanted to repair the mouse skull defect during the second stage. Results: The results showed that skeletal muscle implantation of AAV-BMP4 yielded a large amount of new bone tissues. The ectopic bone tissues can be harvested as a bone graft and can successfully repair the mouse skull defect without any bony overgrowth in situ. Conclusion: The results indicate that the bone tissues purposely generated by AAV-BMP4 in the skeletal muscle may be a new alternative of bone grafting for clinical purposes.
date: 2015-05-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29268/1/art%253A10.1186%252Fs13018-015-0229-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29268/7/licence.txt
identifier:   Tian, K and Qi, M and Wang, L and Li, Z and Xu, J and Li, Y and Liu, G and Wang, B and Huard, J and Li, G  (2015) Two-stage therapeutic utility of ectopically formed bone tissue in skeletal muscle induced by adeno-associated virus containing bone morphogenetic protein-4 gene.  Journal of Orthopaedic Surgery and Research, 10 (1).       
relation: 10.1186/s13018-015-0229-1

relation: http://d-scholarship-dev.library.pitt.edu/26287/
title: How do you haha? LOL through the ages
creator: Collister, Lauren Brittany
description: Sometimes deliberate, sometimes uncontrollable, we laugh out loud to signal our reaction to a range of occurrences, whether it’s a response to a joke we hear, an awkward encounter or an anxious situation. The way we laugh is, according to anthropologist Munro S Edmonson, a “signal of individuality.” And an outburst of laughter is an important enough part of communication that we represent it in text. In a recent The New Yorker article, Sarah Larson wrote about laughter in internet-based communication – the use of hahaha and hehehe, even the jovial hohoho. Larson writes, “The terms of e-laughter – ‘ha ha,’ ‘ho ho,’ ‘hee hee,’ ‘heh’ – are implicitly understood by just about everybody. But, in recent years, there’s been an increasingly popular newcomer: ‘hehe.’” However, even before texting and online chatting, textual representations of laughter – most of which have onomatopoeic forms – have appeared in writing since Chaucer’s time. Like all language, it has merely evolved with our culture and adapted to new technology, becoming in the process far more nuanced – much like the true “spoken” laughter it’s intended to represent.
date: 2015-05-28
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26287/1/licence.txt
identifier:   Collister, Lauren Brittany  (2015) How do you haha? LOL through the ages.  The Conversation.       
relation: https://theconversation.com/how-do-you-haha-lol-through-the-ages-41562

relation: http://d-scholarship-dev.library.pitt.edu/29270/
title: Evaluation of disease burden and response to treatment in adults with type 1 gaucher disease using a validated disease severity scoring system (DS3)
creator: Weinreb, NJ
creator: Finegold, DN
creator: Feingold, E
creator: Zeng, Z
creator: Rosenbloom, BE
creator: Shankar, SP
creator: Amato, D
description: Background: GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses. Methods: We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1. Results: Patient characteristics: N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range. Conclusions: DS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.
date: 2015-05-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29270/1/art%253A10.1186%252Fs13023-015-0280-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29270/7/licence.txt
identifier:   Weinreb, NJ and Finegold, DN and Feingold, E and Zeng, Z and Rosenbloom, BE and Shankar, SP and Amato, D  (2015) Evaluation of disease burden and response to treatment in adults with type 1 gaucher disease using a validated disease severity scoring system (DS3).  Orphanet Journal of Rare Diseases, 10 (1).       
relation: 10.1186/s13023-015-0280-3

relation: http://d-scholarship-dev.library.pitt.edu/28474/
title: Alternating hemiplegia of childhood: Retrospective genetic study and genotype-phenotype correlations in 187 subjects from the US AHCF registry
creator: Viollet, L
creator: Glusman, G
creator: Murphy, KJ
creator: Newcomb, TM
creator: Reyna, SP
creator: Sweney, M
creator: Nelson, B
creator: Andermann, F
creator: Andermann, E
creator: Acsadi, G
creator: Barbano, RL
creator: Brown, C
creator: Brunkow, ME
creator: Chugani, HT
creator: Cheyette, SR
creator: Collins, A
creator: DeBrosse, SD
creator: Galas, D
creator: Friedman, J
creator: Hood, L
creator: Huff, C
creator: Jorde, LB
creator: King, MD
creator: LaSalle, B
creator: Leventer, RJ
creator: Lewelt, AJ
creator: Massart, MB
creator: Mérida, MR
creator: Ptáček, LJ
creator: Roach, JC
creator: Rust, RS
creator: Renault, F
creator: Sanger, TD
creator: De Menezes, MAS
creator: Tennyson, R
creator: Uldall, P
creator: Zhang, Y
creator: Zupanc, M
creator: Xin, W
creator: Silver, K
creator: Swoboda, KJ
description: Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers' questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clustered in exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K (26%) and 11 had G937R (8%) mutations. Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.
date: 2015-05-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28474/1/journal.pone.0127045.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28474/3/licence.txt
identifier:   Viollet, L and Glusman, G and Murphy, KJ and Newcomb, TM and Reyna, SP and Sweney, M and Nelson, B and Andermann, F and Andermann, E and Acsadi, G and Barbano, RL and Brown, C and Brunkow, ME and Chugani, HT and Cheyette, SR and Collins, A and DeBrosse, SD and Galas, D and Friedman, J and Hood, L and Huff, C and Jorde, LB and King, MD and LaSalle, B and Leventer, RJ and Lewelt, AJ and Massart, MB and Mérida, MR and Ptáček, LJ and Roach, JC and Rust, RS and Renault, F and Sanger, TD and De Menezes, MAS and Tennyson, R and Uldall, P and Zhang, Y and Zupanc, M and Xin, W and Silver, K and Swoboda, KJ  (2015) Alternating hemiplegia of childhood: Retrospective genetic study and genotype-phenotype correlations in 187 subjects from the US AHCF registry.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0127045

relation: http://d-scholarship-dev.library.pitt.edu/28476/
title: Modeling and predicting tissue movement and deformation for high intensity focused ultrasound therapy
creator: Liao, X
creator: Yuan, Z
creator: Lai, Q
creator: Guo, J
creator: Zheng, Q
creator: Yu, S
creator: Tong, Q
creator: Si, W
creator: Sun, M
description: Purpose In ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy, the target tissue (such as a tumor) often moves and/or deforms in response to an external force. This problem creates difficulties in treating patients and can lead to the destruction of normal tissue. In order to solve this problem, we present a novel method to model and predict the movement and deformation of the target tissue during ultrasound-guided HIFU therapy. Methods Our method computationally predicts the position of the target tissue under external force. This prediction allows appropriate adjustments in the focal region during the application of HIFU so that the treatment head is kept aligned with the diseased tissue through the course of therapy. To accomplish this goal, we utilize the cow tissue as the experimental target tissue to collect spatial sequences of ultrasound images using the HIFU equipment. A Geodesic Localized Chan-Vese (GLCV) model is developed to segment the target tissue images. A 3D target tissue model is built based on the segmented results. A versatile particle framework is constructed based on Smoothed Particle Hydrodynamics (SPH) to model the movement and deformation of the target tissue. Further, an iterative parameter estimation algorithm is utilized to determine the essential parameters of the versatile particle framework. Finally, the versatile particle framework with the determined parameters is used to estimate the movement and deformation of the target tissue. Results To validate our method, we compare the predicted contours with the ground truth contours. We found that the lowest, highest and average Dice Similarity Coefficient (DSC) values between predicted and ground truth contours were, respectively, 0.9615, 0.9770 and 0.9697. Conclusion Our experimental result indicates that the proposed method can effectively predict the dynamic contours of the moving and deforming tissue during ultrasound-guided HIFU therapy.
date: 2015-05-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28476/1/journal.pone.0127873.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28476/3/licence.txt
identifier:   Liao, X and Yuan, Z and Lai, Q and Guo, J and Zheng, Q and Yu, S and Tong, Q and Si, W and Sun, M  (2015) Modeling and predicting tissue movement and deformation for high intensity focused ultrasound therapy.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0127873

relation: http://d-scholarship-dev.library.pitt.edu/28477/
title: Studying the effects of reproductive hormones and bacterial vaginosis on the glycome of lavage samples from the cervicovaginal cavity
creator: Wang, L
creator: Koppolu, S
creator: Chappell, C
creator: Moncla, BJ
creator: Hillier, SL
creator: Mahal, LK
description: The cervicovaginal fluid (CVF) coating the vaginal epithelium is an important immunological mediator, providing a barrier to infection. Glycosylation of CVF proteins, such as mucins, IgG and S-IgA, plays a critical role in their immunological functions. Although multiple factors, such as hormones and microflora, may influence glycosylation of the CVF, few studies have examined their impact on this important immunological fluid. Herein we analyzed the glycosylation of cervicovaginal lavage (CVL) samples collected from 165 women under different hormonal conditions including: (1) no contraceptive, post-menopausal, (2) no contraceptive, days 1-14 of the menstrual cycle, (3) no contraceptive, days 15-28 of the menstrual cycle, (4) combined-oral contraceptive pills for at least 6 months, (5) depomedroxyprogesterone acetate (Depo-Provera) injections for at least 6 months, (6) levonorgestrel IUD for at least 1 month. Glycomic profiling was obtained using our lectin microarray system, a rapid method to analyze carbohydrate composition. Although some small effects were observed due to hormone levels, the major influence on the glycome was the presence of an altered bacterial cohort due to bacterial vaginosis (BV). Compared to normal women, samples from women with BV contained lower levels of sialic acid and high-mannose glycans in their CVL. The change in high mannose levels was unexpected and may be related to the increased risk of HIV-infection observed in women with BV, as high mannose receptors are a viral entry pathway. Changes in the glycome were also observed with hormonal contraceptive use, in a contraceptive-dependent manner. Overall, microflora had a greater impact on the glycome than hormonal levels, and both of these effects should be more closely examined in future studies given the importance of glycans in the innate immune system.
date: 2015-05-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28477/1/journal.pone.0127021.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28477/3/licence.txt
identifier:   Wang, L and Koppolu, S and Chappell, C and Moncla, BJ and Hillier, SL and Mahal, LK  (2015) Studying the effects of reproductive hormones and bacterial vaginosis on the glycome of lavage samples from the cervicovaginal cavity.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0127021

relation: http://d-scholarship-dev.library.pitt.edu/29272/
title: Programmed cell death and its role in inflammation
creator: Yang, Y
creator: Jiang, G
creator: Zhang, P
creator: Fan, J
description: Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.
date: 2015-05-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29272/1/art%253A10.1186%252Fs40779-015-0039-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29272/7/licence.txt
identifier:   Yang, Y and Jiang, G and Zhang, P and Fan, J  (2015) Programmed cell death and its role in inflammation.  Military Medical Research, 2 (1).   ISSN 2095-7467     
relation: 10.1186/s40779-015-0039-0

relation: http://d-scholarship-dev.library.pitt.edu/29273/
title: Inflammasomes are important mediators of prostatic inflammation associated with BPH
creator: Kashyap, M
creator: Pore, S
creator: Wang, Z
creator: Gingrich, J
creator: Yoshimura, N
creator: Tyagi, P
description: Background: There is mounting evidence to support the role of inflammation in benign prostate hyperplasia (BPH), and a recent study reported expression of inflammasome derived cytokine IL-18 in prostate biopsy of BPH patients. Here we examined the expression of inflammasome-derived cytokines and activation of nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP) 1 inflammasome in a rat model of prostatic inflammation relevant to BPH. Methods: Prostatic inflammation was experimentally induced in three-month-old male Sprague-Dawley rats by intraprostatic injection (50 μL) of either 5 % formalin or saline (sham) into the ventral lobes of prostate. 7 days later, prostate and bladder tissue was harvested for analysis of inflammasome by Western blot, immunohistochemistry and downstream cytokine production by Milliplex. Results: Expression of interleukins, CXC and CC chemokines were elevated 2-15 fold in formalin injected prostate relative to sham. Significant expression of NLRP1 inflammasome components and caspase-1 in prostate were associated with significant elevation of pro and cleaved forms of IL-1β (25.50 ± 1.16 vs 3.05 ± 0.65 pg/mg of protein) and IL-18 (1646.15 ± 182.61 vs 304.67 ± 103.95 pg/mg of protein). Relative to prostate tissue, the cytokine expression in bladder tissue was much lower and did not involve inflammasome activation. Conclusions: Significant upregulation of NLRP1, caspase-1 and downstream cytokines (IL-18 and IL-1β) suggests that a NLRP1 inflammasome is assembled and activated in prostate tissue of this rat model. Recapitulation of findings from human BPH specimens suggests that the inflammasome may perpetuate the inflammatory state associated with BPH. Further clarification of these pathways may offer innovative therapeutic targets for BPH-related inflammation.
date: 2015-05-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29273/1/art%253A10.1186%252Fs12950-015-0082-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29273/7/licence.txt
identifier:   Kashyap, M and Pore, S and Wang, Z and Gingrich, J and Yoshimura, N and Tyagi, P  (2015) Inflammasomes are important mediators of prostatic inflammation associated with BPH.  Journal of Inflammation (United Kingdom), 12 (1).       
relation: 10.1186/s12950-015-0082-3

relation: http://d-scholarship-dev.library.pitt.edu/29274/
title: Lymphoma of the orbit masquerading as Tolosa-Hunt syndrome Neuro-ophthalmology
creator: Shazly, TA
creator: Mitchell, EB
creator: Bonhomme, GR
creator: Schuman, JS
description: Background: Tolosa-Hunt syndrome is a rare clinical syndrome characterized by painful ophthalmoplegia and ipsilateral cranial neuropathies. It is caused by an inflammatory process of unknown etiology. Case presentation: We present a case of a 77-year-old white man with history of Waldenstrom's macroglobulinemia transforming to large B-cell lymphoma who presented to a community physician complaining of 4 months of isolated right retro-orbital pain and later with diplopia, ptosis, 6th nerve and pupil-sparing partial 3rd nerve palsies as well as progressive neurological findings. His clinical course was complicated by debilitating neurological symptoms and multiple hospitalizations leading to a delay in diagnosis caused by incomplete initial workup. Conclusion: This case is a reminder that lymphoproliferative disorders often mimic other neurologic disorders and that Tolosa-Hunt is a rare diagnosis that must be considered a diagnosis of exclusion.
date: 2015-05-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29274/1/art%253A10.1186%252Fs12886-015-0037-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29274/7/licence.txt
identifier:   Shazly, TA and Mitchell, EB and Bonhomme, GR and Schuman, JS  (2015) Lymphoma of the orbit masquerading as Tolosa-Hunt syndrome Neuro-ophthalmology.  BMC Ophthalmology, 15 (1).       
relation: 10.1186/s12886-015-0037-8

relation: http://d-scholarship-dev.library.pitt.edu/25254/
title: Putting Pennsylvania on the App
creator: Barnett, John H
description: Discusses the use of the Clio history website and mobile phone application and how librarians and others can contribute to its contents.
publisher: College & Research Division, Pennsylvania Library Association
date: 2015-05-15
type: Article
type: PeerReviewed
format: other
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25254/1/index.html
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25254/3/licence.txt
identifier:   Barnett, John H  (2015) Putting Pennsylvania on the App.  It's Academic! [CRD-PaLA blog].       
relation: http://crdpala.org/2015/05/15/putting-pennsylvania-on-the-app/

relation: http://d-scholarship-dev.library.pitt.edu/28478/
title: Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons
creator: Grigoryan, S
creator: Yee, MB
creator: Glick, Y
creator: Gerber, D
creator: Kepten, E
creator: Garini, Y
creator: Yang, IH
creator: Kinchington, PR
creator: Goldstein, RS
description: Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.
date: 2015-05-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28478/1/journal.pone.0126081.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28478/3/licence.txt
identifier:   Grigoryan, S and Yee, MB and Glick, Y and Gerber, D and Kepten, E and Garini, Y and Yang, IH and Kinchington, PR and Goldstein, RS  (2015) Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0126081

relation: http://d-scholarship-dev.library.pitt.edu/29276/
title: Current gene therapy using viral vectors for chronic pain
creator: Guedon, JMG
creator: Wu, S
creator: Zheng, X
creator: Churchill, CC
creator: Glorioso, JC
creator: Liu, CH
creator: Liu, S
creator: Vulchanova, L
creator: Bekker, A
creator: Tao, YX
creator: Kinchington, PR
creator: Goins, WF
creator: Fairbanks, CA
creator: Hao, S
description: The complexity of chronic pain and the challenges of pharmacotherapy highlight the importance of development of new approaches to pain management. Gene therapy approaches may be complementary to pharmacotherapy for several advantages. Gene therapy strategies may target specific chronic pain mechanisms in a tissue-specific manner. The present collection of articles features distinct gene therapy approaches targeting specific mechanisms identified as important in the specific pain conditions. Dr. Fairbanks group describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV)), and addresses biodistribution and potential neurotoxicity in pre-clinical models of vector delivery. Dr. Tao group addresses that downregulation of a voltage-gated potassium channel (Kv1.2) contributes to the maintenance of neuropathic pain. Alleviation of chronic pain through restoring Kv1.2 expression in sensory neurons is presented in this review. Drs Goins and Kinchington group describes a strategy to use the replication defective HSV vector to deliver two different gene products (enkephalin and TNF soluble receptor) for the treatment of post-herpetic neuralgia. Dr. Hao group addresses the observation that the pro-inflammatory cytokines are an important shared mechanism underlying both neuropathic pain and the development of opioid analgesic tolerance and withdrawal. The use of gene therapy strategies to enhance expression of the anti-pro-inflammatory cytokines is summarized. Development of multiple gene therapy strategies may have the benefit of targeting specific pathologies associated with distinct chronic pain conditions (by Guest Editors, Drs. C. Fairbanks and S. Hao).
date: 2015-05-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29276/1/art%253A10.1186%252Fs12990-015-0018-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29276/7/licence.txt
identifier:   Guedon, JMG and Wu, S and Zheng, X and Churchill, CC and Glorioso, JC and Liu, CH and Liu, S and Vulchanova, L and Bekker, A and Tao, YX and Kinchington, PR and Goins, WF and Fairbanks, CA and Hao, S  (2015) Current gene therapy using viral vectors for chronic pain.  Molecular Pain, 11 (1).   ISSN 1744-8069     
relation: 10.1186/s12990-015-0018-1

relation: http://d-scholarship-dev.library.pitt.edu/28479/
title: Accounting for dynamic fluctuations across time when examining fMRI test-retest reliability: Analysis of a reward paradigm in the EMBARC study
creator: Chase, HW
creator: Fournier, JC
creator: Greenberg, T
creator: Almeida, JR
creator: Stiffler, R
creator: Zevallos, CR
creator: Aslam, H
creator: Cooper, C
creator: Deckersbach, T
creator: Weyandt, S
creator: Adams, P
creator: Toups, M
creator: Carmody, T
creator: Oquendo, MA
creator: Peltier, S
creator: Fava, M
creator: McGrath, PJ
creator: Weissman, M
creator: Parsey, R
creator: McInnis, MG
creator: Kurian, B
creator: Trivedi, MH
creator: Phillips, ML
description: Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs.
date: 2015-05-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28479/1/journal.pone.0126326.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28479/3/licence.txt
identifier:   Chase, HW and Fournier, JC and Greenberg, T and Almeida, JR and Stiffler, R and Zevallos, CR and Aslam, H and Cooper, C and Deckersbach, T and Weyandt, S and Adams, P and Toups, M and Carmody, T and Oquendo, MA and Peltier, S and Fava, M and McGrath, PJ and Weissman, M and Parsey, R and McInnis, MG and Kurian, B and Trivedi, MH and Phillips, ML  (2015) Accounting for dynamic fluctuations across time when examining fMRI test-retest reliability: Analysis of a reward paradigm in the EMBARC study.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0126326

relation: http://d-scholarship-dev.library.pitt.edu/29277/
title: Mental health first aid training for the Bhutanese refugee community in the United States
creator: Subedi, P
creator: Li, C
creator: Gurung, A
creator: Bizune, D
creator: Dogbey, D
creator: Johnson, CC
creator: Yun, K
description: Background: The aim of this study was to investigate the impact of Mental Health First Aid (MHFA) training for Bhutanese refugee community leaders in the U.S. We hypothesized that training refugee leaders would improve knowledge of mental health problems and treatment process and decrease negative attitudes towards people with mental illness. Methods: One hundred and twenty community leaders participated in MHFA training, of whom 58 had sufficient English proficiency to complete pre- and post-tests. The questionnaires assessed each participant's ability to recognize signs of depression, knowledge about professional help and treatment, and attitudes towards people with mental illness. Results: Between the pre- and post-test, participants showed significant improvement in the recognition of symptoms of depression and expressed beliefs about treatment that became more concordant with those of mental health professionals. However, there was no reduction in negative attitudes towards people with mental illness. Conclusions: MHFA training course is a promising program for Bhutanese refugee communities in the U.S. However, some adaptations may be necessary to ensure that MHFA training is optimized for this community.
date: 2015-05-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29277/1/art%253A10.1186%252Fs13033-015-0012-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29277/7/licence.txt
identifier:   Subedi, P and Li, C and Gurung, A and Bizune, D and Dogbey, D and Johnson, CC and Yun, K  (2015) Mental health first aid training for the Bhutanese refugee community in the United States.  International Journal of Mental Health Systems, 9 (1).       
relation: 10.1186/s13033-015-0012-z

relation: http://d-scholarship-dev.library.pitt.edu/29265/
title: Asthma research and practice: a new journey begins.
creator: Celedon, Juan C
creator: Passalacqua, Giovanni
creator: Canonica, Giorgio Walter
date: 2015-05-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29265/1/art%253A10.1186%252Fs40733-015-0005-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29265/7/licence.txt
identifier:   Celedon, Juan C and Passalacqua, Giovanni and Canonica, Giorgio Walter  (2015) Asthma research and practice: a new journey begins.  Asthma Res Pract, 1.  5 - ?.  ISSN 2054-7064     
relation: 10.1186/s40733-015-0005-3
language: eng

relation: http://d-scholarship-dev.library.pitt.edu/28480/
title: Renal function and coronary microvascular dysfunction in women with symptoms/signs of ischemia
creator: Mohandas, R
creator: Segal, MS
creator: Huo, T
creator: Handberg, EM
creator: Petersen, JW
creator: Johnson, BD
creator: Sopko, G
creator: Merz, CNB
creator: Pepine, CJ
description: © 2015, Public Library of Science. All rights reserved. Objectives: Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. Methods: The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. Results: The median eGFR was 89 ml/min. The eGFR correlated with CFR (r = 0.22; P = 0.002). This association persisted even after covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04-unit decrease in CFR (P = 0.04). There was a strong interaction between eGFR and age (P = 0.006): in those ≥60 years old, GFR was strongly correlated with CFR (r = 0.55; P<0.0001). No significant correlation was noted in those <60 years old. Conclusions: Reduced renal function was significantly associated with lower CFR in women with symptoms and signs of ischemia. Coronary microvascular dysfunction warrants additional study as a mechanism contributing to increased risk of cardiovascular events in CKD.
date: 2015-05-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28480/1/journal.pone.0125374.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28480/3/licence.txt
identifier:   Mohandas, R and Segal, MS and Huo, T and Handberg, EM and Petersen, JW and Johnson, BD and Sopko, G and Merz, CNB and Pepine, CJ  (2015) Renal function and coronary microvascular dysfunction in women with symptoms/signs of ischemia.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0125374

relation: http://d-scholarship-dev.library.pitt.edu/27031/
title: Resurrecting Islam or Cementing Social Hierarchy?: Reexamining the Codification of 'Islamic' Personal Status Law
creator: Hamoudi, Haider Ala
date: 2015-05-07
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27031/1/33ArizJIntlCompL329.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27031/7/licence.txt
identifier:   Hamoudi, Haider Ala  (2015) Resurrecting Islam or Cementing Social Hierarchy?: Reexamining the Codification of 'Islamic' Personal Status Law.  Arizona Journal of International and Comparative Law, 32 (2).       

relation: http://d-scholarship-dev.library.pitt.edu/28481/
title: A phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% Gel (the CHARM-01 study)
creator: Mcgowan, I
creator: Cranston, RD
creator: Duffill, K
creator: Siegel, A
creator: Engstrom, JC
creator: Nikiforov, A
creator: Jacobson, C
creator: Rehman, KK
creator: Elliott, J
creator: Khanukhova, E
creator: Abebe, K
creator: Mauck, C
creator: Spiegel, HML
creator: Dezzutti, CS
creator: Rohan, LC
creator: Marzinke, MA
creator: Hiruy, H
creator: Hendrix, CW
creator: Richardson-Harman, N
creator: Anton, PA
description: Objectives: The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels for rectal application. The vaginal formulation (VF) gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF) gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF) gel was also evaluated in the CHARM-01 study. Methods: Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial. Results: All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/10<sup>6</sup> cells respectively). Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection. Conclusions: All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection. Trial Registration: ClinicalTrials.gov NCT01575405.
date: 2015-05-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28481/1/journal.pone.0125363.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28481/3/licence.txt
identifier:   Mcgowan, I and Cranston, RD and Duffill, K and Siegel, A and Engstrom, JC and Nikiforov, A and Jacobson, C and Rehman, KK and Elliott, J and Khanukhova, E and Abebe, K and Mauck, C and Spiegel, HML and Dezzutti, CS and Rohan, LC and Marzinke, MA and Hiruy, H and Hendrix, CW and Richardson-Harman, N and Anton, PA  (2015) A phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% Gel (the CHARM-01 study).  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0125363

relation: http://d-scholarship-dev.library.pitt.edu/38700/
title: Sociology's Nero Syndrome?
creator: Smith, J
description: Social movement scholarship has failed to help us understand and address the most urgent crisis of our time.
publisher: Mobilizing Ideas
date: 2015-05-04
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/38700/1/licenseagreement_dscholarship.txt
identifier:   Smith, J  (2015) Sociology's Nero Syndrome?         
relation: https://mobilizingideas.wordpress.com/2015/05/04/sociologys-nero-syndrome/

relation: http://d-scholarship-dev.library.pitt.edu/29278/
title: US chiropractors' attitudes, skills and use of evidence-based practice: A cross-sectional national survey
creator: Schneider, MJ
creator: Evans, R
creator: Haas, M
creator: Leach, M
creator: Hawk, C
creator: Long, C
creator: Cramer, GD
creator: Walters, O
creator: Vihstadt, C
creator: Terhorst, L
description: Background: Evidence based practice (EBP) is being increasingly utilized by health care professionals as a means of improving the quality of health care. The introduction of EBP principles into the chiropractic profession is a relatively recent phenomenon. There is currently a lack of information about the EBP literacy level of US chiropractors and the barriers/facilitators to the use of EBP in the chiropractic profession. Methods: A nationwide EBP survey of US chiropractors was administered online (Nov 2012-Mar 2013) utilizing a validated self-report instrument (EBASE) in which three sub-scores are reported: attitudes, skills and use. Means, medians, and frequency distributions for each of the sub-scores were generated. Descriptive statistics were used to analyze the demographic characteristics of the sample. Means and proportions were calculated for all of the responses to each of the questions in the survey. Results: A total of 1,314 US chiropractors completed the EBASE survey; the sample appeared to be representative of the US chiropractic profession. Respondents were predominantly white (94.3%), male (75%), 47 (+/- 11.6) years of age, and in practice for more than 10 years (60%). EBASE sub-score means (possible ranges) were: attitudes, 31.4 (8-40); skills, 44.3 (13-65); and use, 10.3 (0-24). Survey participants generally held favorable attitudes toward EBP, but reported less use of EBP. A minority of participants indicated that EBP coursework (17%) and critical thinking (29%) were a major part of their chiropractic education. The most commonly reported barrier to the use of EBP was "lack of time". Almost 90% of the sample indicated that they were interested in improving their EBP skills. Conclusion: American chiropractors appear similar to chiropractors in other countries, and other health professionals regarding their favorable attitudes towards EBP, while expressing barriers related to EBP skills such as research relevance and lack of time. This suggests that the design of future EBP educational interventions should capitalize on the growing body of EBP implementation research developing in other health disciplines. This will likely include broadening the approach beyond a sole focus on EBP education, and taking a multilevel approach that also targets professional, organizational and health policy domains.
date: 2015-05-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29278/1/art%253A10.1186%252Fs12998-015-0060-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29278/7/licence.txt
identifier:   Schneider, MJ and Evans, R and Haas, M and Leach, M and Hawk, C and Long, C and Cramer, GD and Walters, O and Vihstadt, C and Terhorst, L  (2015) US chiropractors' attitudes, skills and use of evidence-based practice: A cross-sectional national survey.  Chiropractic and Manual Therapies, 23 (1).       
relation: 10.1186/s12998-015-0060-0

relation: http://d-scholarship-dev.library.pitt.edu/25140/
title: Social Media as a Metaphor for Scholarly Communication
creator: Barnett, John H
publisher: College & Research Division, Pennsylvania Library Association
date: 2015-05-03
type: Article
type: NonPeerReviewed
format: other
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25140/1/index.html
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25140/3/licence.txt
identifier:   Barnett, John H  (2015) Social Media as a Metaphor for Scholarly Communication.  It's Academic! [CRD-PaLA blog].       
relation: http://crdpala.org/2015/05/03/social-media-as-a-metaphor-for-scholarly-communication/

relation: http://d-scholarship-dev.library.pitt.edu/28482/
title: Computational characterization of transient strain-transcending immunity against influenza A
creator: Farrow, DC
creator: Burke, DS
creator: Rosenfeld, R
description: The enigmatic observation that the rapidly evolving influenza A (H3N2) virus exhibits, at any given time, a limited standing genetic diversity has been an impetus for much research. One of the first generative computational models to successfully recapitulate this pattern of consistently constrained diversity posits the existence of a strong and short-lived straintranscending immunity. Building on that model, we explored a much broader set of scenarios (parameterizations) of a transient strain-transcending immunity, ran long-term simulations of each such scenario, and assessed its plausibility with respect to a set of known or estimated influenza empirical measures. We evaluated simulated outcomes using a variety of measures, both epidemiological (annual attack rate, epidemic duration, reproductive number, and peak weekly incidence), and evolutionary (pairwise antigenic diversity, fixation rate, most recent common ancestor, and kappa, which quantifies the potential for antigenic evolution). Taking cumulative support from all these measures, we show which parameterizations of strain-transcending immunity are plausible with respect to the set of empirically derived target values. We conclude that strain-transcending immunity which is milder and longer lasting than previously suggested is more congruent with the observed short- and long-term behavior of influenza.
date: 2015-05-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28482/1/journal.pone.0125047.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28482/3/licence.txt
identifier:   Farrow, DC and Burke, DS and Rosenfeld, R  (2015) Computational characterization of transient strain-transcending immunity against influenza A.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0125047

relation: http://d-scholarship-dev.library.pitt.edu/22052/
title: Cost-Effective Resource Provisioning for MapReduce in a Cloud
creator: Palanisamy, B
creator: Singh, A
creator: Liu, L
description: This paper presents a new MapReduce cloud service model, Cura, for provisioning cost-effective MapReduce services in a cloud. In contrast to existing MapReduce cloud services such as a generic compute cloud or a dedicated MapReduce cloud, Cura has a number of unique benefits. First, Cura is designed to provide a cost-effective solution to efficiently handle MapReduce production workloads that have a significant amount of interactive jobs. Second, unlike existing services that require customers to decide the resources to be used for the jobs, Cura leverages MapReduce profiling to automatically create the best cluster configuration for the jobs. While the existing models allow only a per-job resource optimization for the jobs, Cura implements a globally efficient resource allocation scheme that significantly reduces the resource usage cost in the cloud. Third, Cura leverages unique optimization opportunities when dealing with workloads that can withstand some slack. By effectively multiplexing the available cloud resources among the jobs based on the job requirements, Cura achieves significantly lower resource usage costs for the jobs. Cura's core resource management schemes include cost-aware resource provisioning, VM-aware scheduling and online virtual machine reconfiguration. Our experimental results using Facebook-like workload traces show that our techniques lead to more than 80 percent reduction in the cloud compute infrastructure cost with upto 65 percent reduction in job response times.
date: 2015-05-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22052/1/Cura-TPDS-2014.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22052/8/licence.txt
identifier:   Palanisamy, B and Singh, A and Liu, L  (2015) Cost-Effective Resource Provisioning for MapReduce in a Cloud.  IEEE Transactions on Parallel and Distributed Systems, 26 (5).  1265 - 1279.  ISSN 1045-9219     
relation: 10.1109/TPDS.2014.2320498

relation: http://d-scholarship-dev.library.pitt.edu/25651/
title: Dynamic behavior of N-heterocyclic carbene boranes: Boron-carbene bonds in B, B -disubstituted N, N -dimethylimidazol-2-ylidene boranes have substantial rotation barriers
creator: Damodaran, K
creator: Li, X
creator: Pan, X
creator: Curran, DP
description: Dynamic NMR spectroscopy has been used to measure rotation barriers in five B,B-disubstituted 1,3-dimethylimidazol-2-ylidene boranes. The barriers are attributed to the sp<sup>2</sup>-sp<sup>3</sup> bond between C(1) of the N-heterocyclic carbene ring and the boron atom. Bonds to boron atoms bearing a thexyl (1,1,2-trimethylpropyl) group show especially high barriers, ranging from 75-86 kJ mol<sup>-1</sup>. 2-Isopropyl-1,3,5-trimethylbenzene is used as a comparable to help understand the nature and magnitude of the barriers.
date: 2015-05-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25651/1/licence.txt
identifier:   Damodaran, K and Li, X and Pan, X and Curran, DP  (2015) Dynamic behavior of N-heterocyclic carbene boranes: Boron-carbene bonds in B, B -disubstituted N, N -dimethylimidazol-2-ylidene boranes have substantial rotation barriers.  Journal of Organic Chemistry, 80 (9).  4465 - 4469.  ISSN 0022-3263     
relation: 10.1021/acs.joc.5b00324

relation: http://d-scholarship-dev.library.pitt.edu/28473/
title: Exploring the feasibility of multi-site flow cytometric processing of gut associated lymphoid tissue with centralized data analysis for multi-site clinical trials
creator: McGowan, I
creator: Anton, PA
creator: Elliott, J
creator: Cranston, RD
creator: Duffill, K
creator: Althouse, AD
creator: Hawkins, KL
creator: De Rosa, SC
description: The purpose of this study was to determine whether the development of a standardized approach to the collection of intestinal tissue from healthy volunteers, isolation of gut associated lymphoid tissue mucosal mononuclear cells (MMC), and characterization of mucosal T cell phenotypes by flow cytometry was sufficient to minimize differences in the normative ranges of flow parameters generated at two trial sites. Forty healthy male study participants were enrolled in Pittsburgh and Los Angeles. MMC were isolated from rectal biopsies using the same biopsy acquisition and enzymatic digestion protocols. As an additional comparator, peripheral blood mononuclear cells (PBMC) were collected from the study participants. For quality control, cryopreserved PBMC from a single donor were supplied to both sites from a central repository (qPBMC). Using a jointly optimized standard operating procedure, cells were isolated from tissue and blood and stained with monoclonal antibodies targeted to T cell phenotypic markers. Site-specific flow data were analyzed by an independent center which analyzed all data from both sites. Ranges for frequencies for overall CD4+ and CD8+ T cells, derived from the qPBMC samples, were equivalent at both UCLA and MWRI. However, there were significant differences across sites for the majority of T cell activation and memory subsets in qPBMC as well as PBMC and MMC. Standardized protocols to collect, stain, and analyze MMC and PBMC, including centralized analysis, can reduce but not exclude variability in reporting flow data within multi-site studies. Based on these data, centralized processing, flow cytometry, and analysis of samples may provide more robust data across multi-site studies. Centralized processing requires either shipping of fresh samples or cryopreservation and the decision to perform centralized versus site processing needs to take into account the drawbacks and restrictions associated with each method.
date: 2015-05-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28473/1/journal.pone.0126454.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28473/3/licence.txt
identifier:   McGowan, I and Anton, PA and Elliott, J and Cranston, RD and Duffill, K and Althouse, AD and Hawkins, KL and De Rosa, SC  (2015) Exploring the feasibility of multi-site flow cytometric processing of gut associated lymphoid tissue with centralized data analysis for multi-site clinical trials.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0126454

relation: http://d-scholarship-dev.library.pitt.edu/28472/
title: Impact of bacterial vaginosis, as assessed by nugent criteria and hormonal status on glycosidases and lectin binding in cervicovaginal lavage samples
creator: Moncla, BJ
creator: Chappell, CA
creator: Mahal, LK
creator: Debo, BM
creator: Meyn, LA
creator: Hillier, SL
description: The objective of this study was to evaluate the impact of hormonal status and bacterial vaginosis (BV) on the glycosidases present and glycosylation changes as assessed by lectin binding to cervicovaginal lavage constituents. Frozen cervicovaginal lavage samples from a completed study examining the impact of reproductive hormones on the physicochemical properties of vaginal fluid were utilized for the present study. In the parent study, 165 women were characterized as having BV, intermediate or normal microflora using the Nugent criteria. The presence of glycosidases in the samples was determined using quantitative 4-methyl-umbelliferone based assays, and glycosylation was assessed using enzyme linked lectin assays (ELLA). Women with BV had elevated sialidase, α-galactosidase, β-galactosidase and α-glucosidase activities compared to intermediate or normal women (P<0.001, 0.003, 0.006 and 0.042 respectively). The amount of sialic acid (Sambucus nigra, P = 0.003) and high mannose (griffithsin, P<0.001) were reduced, as evaluated by lectin binding, in women with BV. When the data were stratified according to hormonal status, α-glucosidase and griffithsin binding were decreased among postmenopausal women (P<0.02) when compared to premenopausal groups. These data suggest that both hormonal status and BV impact the glycosidases and lectin binding sites present in vaginal fluid. The sialidases present at increased levels in women with BV likely reduce the number of sialic acid binding sites. Other enzymes likely reduce griffithsin binding. The alterations in the glycosidase content, high mannose and sialic acid binding sites in the cervicovaginal fluid associated with bacterial vaginosis may impact susceptibility to viruses, such as HIV, that utilize glycans as a portal of entry.
date: 2015-05-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28472/1/journal.pone.0127091.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28472/3/licence.txt
identifier:   Moncla, BJ and Chappell, CA and Mahal, LK and Debo, BM and Meyn, LA and Hillier, SL  (2015) Impact of bacterial vaginosis, as assessed by nugent criteria and hormonal status on glycosidases and lectin binding in cervicovaginal lavage samples.  PLoS ONE, 10 (5).       
relation: 10.1371/journal.pone.0127091

relation: http://d-scholarship-dev.library.pitt.edu/21727/
title: User participation in an academic social networking service: A survey of open group users on Mendeley
creator: Jeng, W
creator: He, D
creator: Jiang, J
description: Although there are a number of social networking services that specifically target scholars, little has been published about the actual practices and the usage of these so-called academic social networking services (ASNSs). To fill this gap, we explore the populations of academics who engage in social activities using an ASNS; as an indicator of further engagement, we also determine their various motivations for joining a group in ASNSs. Using groups and their members in Mendeley as the platform for our case study, we obtained 146 participant responses from our online survey about users' common activities, usage habits, and motivations for joining groups. Our results show that (a) participants did not engage with social-based features as frequently and actively as they engaged with research-based features, and (b) users who joined more groups seemed to have a stronger motivation to increase their professional visibility and to contribute the research articles that they had read to the group reading list. Our results generate interesting insights into Mendeley's user populations, their activities, and their motivations relative to the social features of Mendeley. We also argue that further design of ASNSs is needed to take greater account of disciplinary differences in scholarly communication and to establish incentive mechanisms for encouraging user participation.
date: 2015-05-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/21727/1/Mendeley_JASIST.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/21727/8/licence.txt
identifier:   Jeng, W and He, D and Jiang, J  (2015) User participation in an academic social networking service: A survey of open group users on Mendeley.  Journal of the Association for Information Science and Technology, 66 (5).  890 - 904.  ISSN 2330-1635     
relation: 10.1002/asi.23225

relation: http://d-scholarship-dev.library.pitt.edu/25343/
title: There Is Always Room for Improvement: PaLRaP's Ongoing Evolution
creator: Barnett, John
creator: Behler, Anne
creator: Reinsfelder, Tom
description: <jats:p>None</jats:p>
publisher: University Library System, University of Pittsburgh
date: 2015-04-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25343/1/94-973-1-PB.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25343/4/licence.txt
identifier:   Barnett, John and Behler, Anne and Reinsfelder, Tom  (2015) There Is Always Room for Improvement: PaLRaP's Ongoing Evolution.  Pennsylvania Libraries: Research &amp; Practice, 3 (1).  1 - 6.      
relation: 10.5195/palrap.2015.94

relation: http://d-scholarship-dev.library.pitt.edu/29370/
title: Recognizing and managing sepsis: What needs to be done?
creator: Yealy, DM
creator: Huang, DT
creator: Delaney, A
creator: Knight, M
creator: Randolph, AG
creator: Daniels, R
creator: Nutbeam, T
description: Sepsis is associated with significant morbidity and mortality if not promptly recognized and treated. Since the development of early goal-directed therapy, mortality rates have decreased, but sepsis remains a major cause of death in patients arriving at the emergency department or staying in hospital. In this forum article, we asked clinicians and researchers with expertise in sepsis care to discuss the importance of rapid detection and treatment of the condition, as well as special considerations in different patient groups.
date: 2015-04-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29370/1/art%253A10.1186%252Fs12916-015-0335-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29370/7/licence.txt
identifier:   Yealy, DM and Huang, DT and Delaney, A and Knight, M and Randolph, AG and Daniels, R and Nutbeam, T  (2015) Recognizing and managing sepsis: What needs to be done?  BMC Medicine, 13 (1).       
relation: 10.1186/s12916-015-0335-2

relation: http://d-scholarship-dev.library.pitt.edu/28483/
title: Blue cone monochromacy: Visual function and efficacy outcome measures for clinical trials
creator: Luo, X
creator: Cideciyan, AV
creator: Iannaccone, A
creator: Roman, AJ
creator: Ditta, LC
creator: Jennings, BJ
creator: Yatsenko, SA
creator: Sheplock, R
creator: Sumaroka, A
creator: Swider, M
creator: Schwartz, SB
creator: Wissinger, B
creator: Kohl, S
creator: Jacobson, SG
description: Background: Blue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the OPN1LW / OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial. Methods: BCM patients (n = 25, ages 5-72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry. Results: Kinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea. Conclusions: BCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial.
date: 2015-04-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28483/1/journal.pone.0125700.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28483/3/licence.txt
identifier:   Luo, X and Cideciyan, AV and Iannaccone, A and Roman, AJ and Ditta, LC and Jennings, BJ and Yatsenko, SA and Sheplock, R and Sumaroka, A and Swider, M and Schwartz, SB and Wissinger, B and Kohl, S and Jacobson, SG  (2015) Blue cone monochromacy: Visual function and efficacy outcome measures for clinical trials.  PLoS ONE, 10 (4).       
relation: 10.1371/journal.pone.0125700

relation: http://d-scholarship-dev.library.pitt.edu/29372/
title: Neuroprotection in acute brain injury: An up-to-date review
creator: Stocchetti, N
creator: Taccone, FS
creator: Citerio, G
creator: Pepe, PE
creator: Roux, PD
creator: Oddo, M
creator: Polderman, KH
creator: Stevens, RD
creator: Barsan, W
creator: Maas, AIR
creator: Meyfroidt, G
creator: Bell, MJ
creator: Silbergleit, R
creator: Vespa, PM
creator: Faden, AI
creator: Helbok, R
creator: Tisherman, S
creator: Zanier, ER
creator: Valenzuela, T
creator: Wendon, J
creator: Menon, DK
creator: Vincent, JL
description: Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.
date: 2015-04-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29372/1/art%253A10.1186%252Fs13054-015-0887-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29372/7/licence.txt
identifier:   Stocchetti, N and Taccone, FS and Citerio, G and Pepe, PE and Roux, PD and Oddo, M and Polderman, KH and Stevens, RD and Barsan, W and Maas, AIR and Meyfroidt, G and Bell, MJ and Silbergleit, R and Vespa, PM and Faden, AI and Helbok, R and Tisherman, S and Zanier, ER and Valenzuela, T and Wendon, J and Menon, DK and Vincent, JL  (2015) Neuroprotection in acute brain injury: An up-to-date review.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0887-8

relation: http://d-scholarship-dev.library.pitt.edu/28484/
title: AMDE-1 is a dual function chemical for autophagy activation and inhibition
creator: Li, M
creator: Yang, Z
creator: Vollmer, LL
creator: Gao, Y
creator: Fu, Y
creator: Liu, C
creator: Chen, X
creator: Liu, P
creator: Vogt, A
creator: Yin, XM
description: Autophagy is the process by which cytosolic components and organelles are delivered to the lysosome for degradation. Autophagy plays important roles in cellular homeostasis and disease pathogenesis. Small chemical molecules that can modulate autophagy activity may have pharmacological value for treating diseases. Using a GFP-LC3-based high content screening assay we identified a novel chemical that is able to modulate autophagy at both initiation and degradation levels. This molecule, termed as Autophagy Modulator with Dual Effect-1 (AMDE-1), triggered autophagy in an Atg5-dependent manner, recruiting Atg16 to the pre-autophagosomal site and causing LC3 lipidation. AMDE-1 induced autophagy through the activation of AMPK, which inactivated mTORC1 and activated ULK1. AMDE-1did not affect MAP kinase, JNK or oxidative stress signaling for autophagy induction. Surprisingly, treatment with AMDE-1 resulted in impairment in autophagic flux and inhibition of long-lived protein degradation. This inhibition was correlated with a reduction in lysosomal degradation capacity but not with autophagosome-lysosome fusion. Further analysis indicated that AMDE-1 caused a reduction in lysosome acidity and lysosomal proteolytic activity, suggesting that it suppressed general lysosome function. AMDE-1 thus also impaired endocytosis-mediated EGF receptor degradation. The dual effects of AMDE-1 on autophagy induction and lysosomal degradation suggested that its net effect would likely lead to autophagic stress and lysosome dysfunction, and therefore cell death. Indeed, AMDE-1 triggered necroptosis and was preferentially cytotoxic to cancer cells. In conclusion, this study identified a new class of autophagy modulators with dual effects, which can be explored for potential uses in cancer therapy.
date: 2015-04-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28484/1/journal.pone.0122083.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28484/3/licence.txt
identifier:   Li, M and Yang, Z and Vollmer, LL and Gao, Y and Fu, Y and Liu, C and Chen, X and Liu, P and Vogt, A and Yin, XM  (2015) AMDE-1 is a dual function chemical for autophagy activation and inhibition.  PLoS ONE, 10 (4).       
relation: 10.1371/journal.pone.0122083

relation: http://d-scholarship-dev.library.pitt.edu/29376/
title: Veno-venous extracorporeal CO<inf>2</inf> removal for the treatment of severe respiratory acidosis
creator: Cove, ME
creator: Federspiel, WJ
date: 2015-04-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29376/1/art%253A10.1186%252Fs13054-015-0769-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29376/7/licence.txt
identifier:   Cove, ME and Federspiel, WJ  (2015) Veno-venous extracorporeal CO<inf>2</inf> removal for the treatment of severe respiratory acidosis.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0769-0

relation: http://d-scholarship-dev.library.pitt.edu/28485/
title: Weaker dental enamel explains dental decay
creator: Vieira, AR
creator: Gibson, CW
creator: Deeley, K
creator: Xue, H
creator: Li, Y
description: Dental caries continues to be the most prevalent bacteria-mediated non-contagious disease of humankind. Dental professionals assert the disease can be explained by poor oral hygiene and a diet rich in sugars but this does not account for caries free individuals exposed to the same risk factors. In order to test the hypothesis that amount of amelogenin during enamel development can influence caries susceptibility, we generated multiple strains of mice with varying levels of available amelogenin during dental development. Mechanical tests showed that dental enamel developed with less amelogenin is "weaker" while the dental enamel of animals over-expressing amelogenin appears to be more resistant to acid dissolution.
date: 2015-04-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28485/1/journal.pone.0124236.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28485/3/licence.txt
identifier:   Vieira, AR and Gibson, CW and Deeley, K and Xue, H and Li, Y  (2015) Weaker dental enamel explains dental decay.  PLoS ONE, 10 (4).       
relation: 10.1371/journal.pone.0124236

relation: http://d-scholarship-dev.library.pitt.edu/25462/
title: Leading New Lawyers: Leadership and Legal Education
creator: Madison, Michael J
description: Lawyers may become leaders, but leaders also may become lawyers. The path to leadership can begin in law school. This short essay describes a leadership development course developed and implemented at a law school over the last four years.
date: 2015-04-16
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25462/4/Madison833pdf.pdf
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25462/1/Madison_Leadership_Essay-IPI_WPS_series.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25462/10/licence.txt
identifier:   Madison, Michael J  (2015) Leading New Lawyers: Leadership and Legal Education.        (Unpublished)  
relation: http://ssrn.com/abstract=2595351

relation: http://d-scholarship-dev.library.pitt.edu/29378/
title: Gene-and stem cell-based therapeutics for cartilage regeneration and repair
creator: Tang, Y
creator: Wang, B
description: Cell-based regeneration of damaged or diseased articular cartilage still faces significant clinical challenge due to inadequate environmental regulation of stem cell proliferation and chondrogenic differentiation. The role of insulin-like growth factor in critical steps of human bone marrow-derived mesenchymal stem cell chondrogenesis has potential in optimizing the therapeutic use of mesenchymal stem cells in cartilage disorders. In addition to the previously described benefits of recombinant adeno-associated viral vector for in vivo gene therapy, demonstrated by Frisch and colleagues, such vector is also a safe and efficient delivery system for the genetic modification of human bone marrow-derived mesenchymal stem cells via ex vivo insulin-like growth factor 1 gene transfer, so that implanted mesenchymal stem cells continuously release a therapeutic level of insulin-like growth factor 1 to achieve sustained mesenchymal stem cell chondrogenesis for cartilage regeneration.
date: 2015-04-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29378/1/art%253A10.1186%252Fs13287-015-0058-5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29378/7/licence.txt
identifier:   Tang, Y and Wang, B  (2015) Gene-and stem cell-based therapeutics for cartilage regeneration and repair.  Stem Cell Research and Therapy, 6 (1).       
relation: 10.1186/s13287-015-0058-5

relation: http://d-scholarship-dev.library.pitt.edu/28585/
title: The Availability and Consistency of Dengue Surveillance Data Provided Online by the World Health Organization
creator: Ruberto, I
creator: Marques, E
creator: Burke, DS
creator: Van Panhuis, WG
description: Background: The use of high quality disease surveillance data has become increasingly important for public health action against new threats. In response, countries have developed a wide range of disease surveillance systems enabled by technological advancements. The heterogeneity and complexity of country data systems have caused a growing need for international organizations such as the World Health Organization (WHO) to coordinate the standardization, integration, and dissemination of country disease data at the global level for research and policy. The availability and consistency of currently available disease surveillance data at the global level are unclear. We investigated this for dengue surveillance data provided online by the WHO. Methods and Findings: We extracted all dengue surveillance data provided online by WHO Headquarters and Regional Offices (RO’s). We assessed the availability and consistency of these data by comparing indicators within and between sources. We also assessed the consistency of dengue data provided online by two example countries (Brazil and Indonesia). Data were available from WHO for 100 countries since 1955 representing a total of 23 million dengue cases and 82 thousand deaths ever reported to WHO. The availability of data on DengueNet and some RO’s declined dramatically after 2005. Consistency was lacking between sources (84% across all indicators representing a discrepancy of almost half a million cases). Within sources, data at high spatial resolution were often incomplete. Conclusions: The decline of publicly available, integrated dengue surveillance data at the global level will limit opportunities for research, policy, and advocacy. A new financial and operational framework will be necessary for innovation and for the continued availability of integrated country disease data at the global level.
date: 2015-04-14
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28585/1/journal.pntd.0003511.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28585/3/licence.txt
identifier:   Ruberto, I and Marques, E and Burke, DS and Van Panhuis, WG  (2015) The Availability and Consistency of Dengue Surveillance Data Provided Online by the World Health Organization.  PLoS Neglected Tropical Diseases, 9 (4).   ISSN 1935-2727     
relation: 10.1371/journal.pntd.0003511

relation: http://d-scholarship-dev.library.pitt.edu/28583/
title: A DNA Vaccine against Yellow Fever Virus: Development and Evaluation
creator: Maciel, M
creator: Cruz, FDSP
creator: Cordeiro, MT
creator: da Motta, MA
creator: Cassemiro, KMSDM
creator: Maia, RDCC
creator: de Figueiredo, RCBQ
creator: Galler, R
creator: Freire, MDS
creator: August, JT
creator: Marques, ETA
creator: Dhalia, R
description: Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.
date: 2015-04-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28583/1/journal.pntd.0003693.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28583/3/licence.txt
identifier:   Maciel, M and Cruz, FDSP and Cordeiro, MT and da Motta, MA and Cassemiro, KMSDM and Maia, RDCC and de Figueiredo, RCBQ and Galler, R and Freire, MDS and August, JT and Marques, ETA and Dhalia, R  (2015) A DNA Vaccine against Yellow Fever Virus: Development and Evaluation.  PLoS Neglected Tropical Diseases, 9 (4).   ISSN 1935-2727     
relation: 10.1371/journal.pntd.0003693

relation: http://d-scholarship-dev.library.pitt.edu/28486/
title: First-principles calculations, experimental study, and thermodynamic modeling of the Al-Co-Cr system
creator: Liu, XL
creator: Gheno, T
creator: Lindahl, BB
creator: Lindwall, G
creator: Gleeson, B
creator: Liu, ZK
description: The phase relations and thermodynamic properties of the condensed Al-Co-Cr ternary alloy system are investigated using first-principles calculations based on density functional theory (DFT) and phase-equilibria experiments that led to X-ray diffraction (XRD) and electron probe micro-analysis (EPMA) measurements. A thermodynamic description is developed by means of the calculations of phase diagrams (CALPHAD) method using experimental and computational data from the present work and the literature. Emphasis is placed on modeling the bcc-A2, B2, fcc-γ, and tetragonal-σ phases in the temperature range of 1173 to 1623 K. Liquid, bcc-A2 and fcc-γ phases are modeled using substitutional solution descriptions. First-principles special quasirandom structures (SQS) calculations predict a large bcc-A2 (disordered)/B2 (ordered) miscibility gap, in agreement with experiments. A partitioning model is then used for the A2/B2 phase to effectively describe the order-disorder transitions. The critically assessed thermodynamic description describes all phase equilibria data well. A2/B2 transitions are also shown to agree well with previous experimental findings.
date: 2015-04-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28486/1/journal.pone.0121386.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28486/3/licence.txt
identifier:   Liu, XL and Gheno, T and Lindahl, BB and Lindwall, G and Gleeson, B and Liu, ZK  (2015) First-principles calculations, experimental study, and thermodynamic modeling of the Al-Co-Cr system.  PLoS ONE, 10 (4).       
relation: 10.1371/journal.pone.0121386

relation: http://d-scholarship-dev.library.pitt.edu/29379/
title: Perioperative fluid therapy: A statement from the international Fluid Optimization Group
creator: Navarro, LHC
creator: Bloomstone, JA
creator: Auler, JOC
creator: Cannesson, M
creator: Rocca, GD
creator: Gan, TJ
creator: Kinsky, M
creator: Magder, S
creator: Miller, TE
creator: Mythen, M
creator: Perel, A
creator: Reuter, DA
creator: Pinsky, MR
creator: Kramer, GC
description: © 2015 Navarro et al.; licensee BioMed Central. Background: Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered.Methods: Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them.Results: The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration.Conclusions: We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.
date: 2015-04-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29379/1/art%253A10.1186%252Fs13741-015-0014-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29379/7/licence.txt
identifier:   Navarro, LHC and Bloomstone, JA and Auler, JOC and Cannesson, M and Rocca, GD and Gan, TJ and Kinsky, M and Magder, S and Miller, TE and Mythen, M and Perel, A and Reuter, DA and Pinsky, MR and Kramer, GC  (2015) Perioperative fluid therapy: A statement from the international Fluid Optimization Group.  Perioperative Medicine, 4 (1).       
relation: 10.1186/s13741-015-0014-z

relation: http://d-scholarship-dev.library.pitt.edu/28487/
title: Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis
creator: Conti, HR
creator: Whibley, N
creator: Coleman, BM
creator: Garg, AV
creator: Jaycox, JR
creator: Gaffen, SL
description: Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C . albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the bestcharacterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C . albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.
date: 2015-04-07
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28487/1/journal.pone.0122807.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28487/3/licence.txt
identifier:   Conti, HR and Whibley, N and Coleman, BM and Garg, AV and Jaycox, JR and Gaffen, SL  (2015) Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis.  PLoS ONE, 10 (4).       
relation: 10.1371/journal.pone.0122807

relation: http://d-scholarship-dev.library.pitt.edu/24590/
title: Emoticons and symbols aren’t ruining language – they’re revolutionizing it
creator: Collister, Lauren Brittany
description: In many casual discussions of language and the internet, it’s not uncommon to hear about how such “textspeak ruins language” – how technology has made everybody lazy with their speech and writing. Major media outlets such as the LA Times, the BBC and The Daily Mail have all bemoaned the ways in which people communicate through technology. Of course, language does change when it’s used to text or write messages on the internet. It’s even become the focus of the field of linguistics known as Computer-Mediated Communication (CMC). Although it specifies computers in its name, CMC refers to the study of interaction facilitated by technology like computers, mobile phones and tablets. And contrary to the idea that these innovations are corrupting language, they actually demonstrate a creative repurposing of symbols and marks to a new age of technology. These evolutions of language are swift, clever and context-specific, illustrating the flexibility of the language to communicate nonverbal meaning in a nuanced, efficient manner.
date: 2015-04-06
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24590/1/licence.txt
identifier:   Collister, Lauren Brittany  (2015) Emoticons and symbols aren’t ruining language – they’re revolutionizing it.  The Conversation.       
relation: https://theconversation.com/emoticons-and-symbols-arent-ruining-language-theyre-revolutionizing-it-38408

relation: http://d-scholarship-dev.library.pitt.edu/29382/
title: Renal replacement therapy in acute kidney injury: Controversy and consensus
creator: Ronco, C
creator: Ricci, Z
creator: De Backer, D
creator: Kellum, JA
creator: Taccone, FS
creator: Joannidis, M
creator: Pickkers, P
creator: Cantaluppi, V
creator: Turani, F
creator: Saudan, P
creator: Bellomo, R
creator: Joannes-Boyau, O
creator: Antonelli, M
creator: Payen, D
creator: Prowle, JR
creator: Vincent, JL
description: Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.
date: 2015-04-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29382/1/art%253A10.1186%252Fs13054-015-0850-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29382/7/licence.txt
identifier:   Ronco, C and Ricci, Z and De Backer, D and Kellum, JA and Taccone, FS and Joannidis, M and Pickkers, P and Cantaluppi, V and Turani, F and Saudan, P and Bellomo, R and Joannes-Boyau, O and Antonelli, M and Payen, D and Prowle, JR and Vincent, JL  (2015) Renal replacement therapy in acute kidney injury: Controversy and consensus.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0850-8

relation: http://d-scholarship-dev.library.pitt.edu/25411/
title: Automatic selection of landmarks for navigation guidance
creator: Zhu, R
creator: Karimi, HA
description: Although current navigation services provide significant benefits to people's mobility, the turn-by-turn instructions they provide are sometimes ineffective. These instructions require people to maintain a high level of attention and cognitive workload while performing distance or angle measurements on their own mental map. To overcome this problem, landmarks have been identified as playing a major role in turn-by-turn instructions. This requires the availability of landmarks in navigation databases. Landmarks are commonly selected manually, which involves time-consuming and tedious tasks. Automatic selection of landmarks has recently gained the attention of researchers but currently there are only a few techniques that can select appropriate landmarks. In this article, we present a technique based on a neural network model, where both static and dynamic features are used for selecting landmarks automatically. To train and test this model, two labeling approaches, manual labeling and rule-based labeling, are also discussed. Experiments on the developed technique were conducted and the results show that rule-based labeling has a precision of approximately 90%, which makes the technique suitable and reliable for automatic selection of landmarks.
date: 2015-04-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25411/1/licence.txt
identifier:   Zhu, R and Karimi, HA  (2015) Automatic selection of landmarks for navigation guidance.  Transactions in GIS, 19 (2).  247 - 261.  ISSN 1361-1682     
relation: 10.1111/tgis.12095

relation: http://d-scholarship-dev.library.pitt.edu/24681/
title: Call to Action: Creating Tomorrow's Libraries Today
creator: Miller, RG
publisher: American Library Association
date: 2015-04-01
type: Article
type: PeerReviewed
format: application/msword
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24681/1/Call_to_Action.docx
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24681/3/licence.txt
identifier:   Miller, RG  (2015) Call to Action: Creating Tomorrow's Libraries Today.  Choice Reviews Online, 52 (08).  1262 - 1263.  ISSN 0009-4978     
relation: 10.5860/choice.52.08.1262
language: en

relation: http://d-scholarship-dev.library.pitt.edu/20001/
title: Interference fracturing: Nonuniform distributions of perforation clusters that promote simultaneous growth of multiple hydraulic fractures
creator: Peirce, AP
creator: Bunger, AP
description: One of the important hurdles in horizontal-well stimulation is the generation of hydraulic fractures (HFs) from all perforation clusters within a given stage, despite the challenges posed by stress shadowing and reservoir variability. In this paper, we use a newly developed, fully coupled, parallel-planar 3D HF model to investigate the potential to minimize the negative impact of stress shadowing and thereby to promote more-uniform fracture growth across an array of HFs by adjusting the location of the perforation clusters. In this model, the HFs are assumed to evolve in an array of parallel planes with full 3D stress coupling while the constant fluid influx into the wellbore is dynamically partitioned to each fracture so that the wellbore pressure is the same throughout the array. The model confirms the phenomenon of inner-fracture suppression because of stress shadowing when the perforation clusters are uniformly distributed. Indeed, the localization of the fracture growth to the outer fractures is so dominant that the total fractured area generated by uniform arrays is largely independent of the number of perforation clusters. However, numerical experiments indicate that certain nonuniform cluster spacings promote a profound improvement in the even development of fracture growth. Identifying this effect relies on this new model's ability to capture the full hydrodynamical coupling between the simultaneously evolving HFs in their transition from radial to Perkins-Kern-Nordgren (PKN)-like geometries (Perkins and Kern 1961; Nordgren 1972).
date: 2015-04-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/20001/1/Peirce_Bunger_SPE_HFTC_2014_v5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/20001/8/licence.txt
identifier:   Peirce, AP and Bunger, AP  (2015) Interference fracturing: Nonuniform distributions of perforation clusters that promote simultaneous growth of multiple hydraulic fractures.  SPE Journal, 20 (2).  384 - 395.  ISSN 1086-055X     
relation: 10.2118/172500-PA

relation: http://d-scholarship-dev.library.pitt.edu/29383/
title: Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer
creator: Macke, RA
creator: Schuchert, MJ
creator: Odell, DD
creator: Wilson, DO
creator: Luketich, JD
creator: Landreneau, RJ
description: Background: A suggested benefit of sublobar resection for stage I non-small cell lung cancer (NSCLC) compared to lobectomy is a relative preservation of pulmonary function. Very little objective data exist, however, supporting this supposition. We sought to evaluate the relative impact of both anatomic segmental and lobar resection on pulmonary function in patients with resected clinical stage I NSCLC. Methods: The records of 159 disease-free patients who underwent anatomic segmentectomy (n = 89) and lobectomy (n = 70) for the treatment of stage I NSCLC with pre- and postoperative pulmonary function tests performed between 6 to 36 months after resection were retrospectively reviewed. Changes in forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were analyzed based upon the number of anatomic pulmonary segments removed: 1-2 segments (n = 77) or 3-5 segments (n = 82). Results: Preoperative pulmonary function was worse in the lesser resection cohort (1-2 segments) compared to the greater resection group (3-5 segments) (FEV1(%predicted): 79% vs. 85%, p = 0.038; DLCO(%predicted): 63% vs. 73%, p = 0.010). A greater decline in FEV1 was noted in patients undergoing resection of 3-5 segments (FEV1 (observed): 0.1 L vs. 0.3 L, p = 0.003; and FEV1 (% predicted): 4.3% vs. 8.2%, p = 0.055). Changes in DLCO followed this same trend (DLCO(observed): 1.3 vs. 2.4 mL/min/mmHg, p = 0.015; and DLCO(% predicted): 3.6% vs. 5.9%, p = 0.280). Conclusions: Parenchymal-sparing resections resulted in better preservation of pulmonary function at a median of one year, suggesting a long-term functional benefit with small anatomic segmental resections (1-2 segments). Prospective studies to evaluate measurable functional changes, as well as quality of life, between segmentectomy and lobectomy with a larger patient cohort appear justified.
date: 2015-04-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29383/1/art%253A10.1186%252Fs13019-015-0253-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29383/7/licence.txt
identifier:   Macke, RA and Schuchert, MJ and Odell, DD and Wilson, DO and Luketich, JD and Landreneau, RJ  (2015) Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer.  Journal of Cardiothoracic Surgery, 10 (1).       
relation: 10.1186/s13019-015-0253-6

relation: http://d-scholarship-dev.library.pitt.edu/27179/
title: Ingestive Classics no. 10: Ed Stricker, Joe Verbalis and Oxytocin.
creator: Rinaman, Linda
date: 2015-04
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27179/1/licence.txt
identifier:   Rinaman, Linda  (2015) Ingestive Classics no. 10: Ed Stricker, Joe Verbalis and Oxytocin.  Society for the Study of Ingestive Behavior.       

relation: http://d-scholarship-dev.library.pitt.edu/25089/
title: The Opportunity Costs of Remaining a Book Discipline
creator: Putnam, Lara
description: Essay suggests that technological shifts impacting scholarly communication should encourage us to question the opportunity costs of insisting on maintaining the 100,000 word monograph as the core unit of published scholarship acknowledged for purposes of tenure and promotion within the historical profession. Consideration of visibility and access, the benefits of peer review, and flexibility to reward outreach may all advocate in favor of a move towards "book and/or article discipline" status.
publisher: American Historical Review
date: 2015-04
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25089/1/Lara_Putnam-Book_Discipline.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25089/4/licence.txt
identifier:   Putnam, Lara  (2015) The Opportunity Costs of Remaining a Book Discipline.  Perspectives on History, 53 (4).  20 - 21.  ISSN 1940-8048     
relation: https://www.historians.org/publications-and-directories/perspectives-on-history/april-2015/the-opportunity-costs-of-remaining-a-book-discipline

relation: http://d-scholarship-dev.library.pitt.edu/25500/
title: Improving the Performance of Multi-Hop Wireless Networks by Selective Transmission Power Control
creator: Kim, Tae-Hoon
creator: Tipper, David
creator: Krishnamurthy, Prashant
publisher: The Korean Institute of Information and Communication Sciences
date: 2015-03-31
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25500/1/130102.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25500/4/licence.txt
identifier:   Kim, Tae-Hoon and Tipper, David and Krishnamurthy, Prashant  (2015) Improving the Performance of Multi-Hop Wireless Networks by Selective Transmission Power Control.  Journal of information and communication convergence engineering, 13 (1).  7 - 14.  ISSN 2234-8255     
relation: 10.6109/jicce.2015.13.1.007
language: en

relation: http://d-scholarship-dev.library.pitt.edu/28489/
title: Loss of Pol32 in Drosophila melanogaster causes chromosome instability and suppresses variegation
creator: Tritto, P
creator: Palumbo, V
creator: Micale, L
creator: Marzulli, M
creator: Bozzetti, MP
creator: Specchia, V
creator: Palumbo, G
creator: Pimpinelli, S
creator: Berloco, M
description: Pol32 is an accessory subunit of the replicative DNA Polymerase δ and of the translesion Polymerase ζ. Pol32 is involved in DNA replication, recombination and repair. Pol32' s participation in high- and low-fidelity processes, together with the phenotypes arising from its disruption, imply multiple roles for this subunit within eukaryotic cells, not all of which have been fully elucidated. Using pol32 null mutants and two partial loss-of-function alleles pol32rd1 and pol32rds in Drosophila melanogaster, we show that Pol32 plays an essential role in promoting genome stability. Pol32 is essential to ensure DNA replication in early embryogenesis and it participates in the repair of mitotic chromosome breakage. In addition we found that pol32 mutantssuppress position effect variegation, suggesting a role for Pol32 in chromatin architecture.
date: 2015-03-31
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28489/1/journal.pone.0120859.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28489/3/licence.txt
identifier:   Tritto, P and Palumbo, V and Micale, L and Marzulli, M and Bozzetti, MP and Specchia, V and Palumbo, G and Pimpinelli, S and Berloco, M  (2015) Loss of Pol32 in Drosophila melanogaster causes chromosome instability and suppresses variegation.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120859

relation: http://d-scholarship-dev.library.pitt.edu/28488/
title: MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model
creator: Zaidi, AH
creator: Saldin, LT
creator: Kelly, LA
creator: Bergal, L
creator: Londono, R
creator: Kosovec, JE
creator: Komatsu, Y
creator: Kasi, PM
creator: Shetty, AA
creator: Keane, TJ
creator: Thakkar, SJ
creator: Huleihel, L
creator: Landreneau, RJ
creator: Badylak, SF
creator: Jobe, BA
description: Objective: To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). Background: The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. Methods: The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNAlinked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. Results: The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-PLOS 92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. Conclusion: In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.
date: 2015-03-31
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28488/1/journal.pone.0122375.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28488/3/licence.txt
identifier:   Zaidi, AH and Saldin, LT and Kelly, LA and Bergal, L and Londono, R and Kosovec, JE and Komatsu, Y and Kasi, PM and Shetty, AA and Keane, TJ and Thakkar, SJ and Huleihel, L and Landreneau, RJ and Badylak, SF and Jobe, BA  (2015) MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0122375

relation: http://d-scholarship-dev.library.pitt.edu/28491/
title: Involvement of large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle
creator: Wei, MY
creator: Xue, L
creator: Tan, L
creator: Sai, WB
creator: Liu, XC
creator: Jiang, QJ
creator: Shen, J
creator: Peng, YB
creator: Zhao, P
creator: Yu, MF
creator: Chen, W
creator: Ma, LQ
creator: Zhai, K
creator: Zou, C
creator: Guo, D
creator: Qin, G
creator: Zheng, YM
creator: Wang, YX
creator: Ji, G
creator: Liu, QH
description: The participation of large-conductance Ca2+ activated K+ channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked spontaneous transient outward currents (STOCs) in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca2+ sparks and caffeine-induced global Ca2+ increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs). We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH). Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax), BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro.
date: 2015-03-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28491/1/journal.pone.0121566.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28491/3/licence.txt
identifier:   Wei, MY and Xue, L and Tan, L and Sai, WB and Liu, XC and Jiang, QJ and Shen, J and Peng, YB and Zhao, P and Yu, MF and Chen, W and Ma, LQ and Zhai, K and Zou, C and Guo, D and Qin, G and Zheng, YM and Wang, YX and Ji, G and Liu, QH  (2015) Involvement of large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0121566

relation: http://d-scholarship-dev.library.pitt.edu/29384/
title: Residential environment and breast cancer incidence and mortality: A systematic review and meta-analysis
creator: Akinyemiju, TF
creator: Genkinger, JM
creator: Farhat, M
creator: Wilson, A
creator: Gary-Webb, TL
creator: Tehranifar, P
description: Background: Factors beyond the individual level such as those characterizing the residential environment may be important to breast cancer outcomes. We provide a systematic review and results of meta-analysis of the published empirical literature on the associations between breast cancer risk and mortality and features of the residential environment. Methods: Using PRISMA guidelines, we searched four electronic databases and manually searched the references of selected articles for studies that were published before June 2013. We selected English language articles that presented data on adult breast cancer incidence or mortality in relation to at least one area-based residential (ABR) independent variable. Results: We reviewed 31 eligible studies, and observed variations in ABR construct definition and measurement, study design, and analytic approach. The most common ABR measures were indicators of socioeconomic status (SES) (e.g., income, education, summary measures of several SES indicators or composite SES). We observed positive associations between breast cancer incidence and urbanization (Pooled RR for urban vs. rural: 1.09. 95% CI: 1.01, 1.19), ABR income (Pooled RR for highest vs. lowest ABR income: 1.17, 95% CI: 1.15, 1.19) and ABR composite SES (Pooled RR for highest vs. lowest ABR composite SES: 1.25, 95% CI: 1.08, 1.44). We did not observe consistent associations between any ABR measures and breast cancer mortality. Conclusions: The findings suggest modest positive associations between urbanization and residential area socioeconomic environment and breast cancer incidence. Further studies should address conceptual and methodological gaps in the current publications to enable inference regarding the influence of the residential environment on breast cancer.
date: 2015-03-28
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29384/1/art%253A10.1186%252Fs12885-015-1098-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29384/7/licence.txt
identifier:   Akinyemiju, TF and Genkinger, JM and Farhat, M and Wilson, A and Gary-Webb, TL and Tehranifar, P  (2015) Residential environment and breast cancer incidence and mortality: A systematic review and meta-analysis.  BMC Cancer, 15 (1).       
relation: 10.1186/s12885-015-1098-z

relation: http://d-scholarship-dev.library.pitt.edu/28492/
title: Expression Quantitative Trait Loci (eQTL) mapping in Puerto Rican children
creator: Chen, W
creator: Brehm, JM
creator: Lin, J
creator: Wang, T
creator: Forno, E
creator: Acosta-Pérez, E
creator: Boutaoui, N
creator: Canino, G
creator: Celedón, JC
description: Background: Expression quantitative trait loci (eQTL) have been identified using tissue or cell samples from diverse human populations, thus enhancing our understanding of regulation of gene expression. However, few studies have attempted to identify eQTL in racially admixed populations such as Hispanics. Methods: We performed a systematic eQTL study to identify regulatory variants of gene expression in whole blood from 121 Puerto Rican children with (n = 63) and without (n = 58) asthma. Genome-wide genotyping was conducted using the Illumina Omni2.5M Bead Chip, and gene expression was assessed using the Illumina HT-12 microarray. After completing quality control, we performed a pair-wise genome analysis of ∼15 K transcripts and ∼1.3 M SNPs for both local and distal effects. This analysis was conducted under a regression framework adjusting for age, gender and principal components derived from both genotypic and mRNA data. We used a false discovery rate (FDR) approach to identify significant eQTL signals, which were next compared to top eQTL signals from existing eQTL databases. We then performed a pathway analysis for our top genes. Results: We identified 36,720 local pairs in 3,391 unique genes and 1,851 distal pairs in 446 unique genes at FDR <0.05, corresponding to unadjusted P values lower than 1.5x10-4 and 4.5x10-9, respectively. A significant proportion of genes identified in our study overlapped with those identified in previous studies. We also found an enrichment of disease-related genes in our eQTL list. Conclusions: We present results from the first eQTL study in Puerto Rican children, who are members of a unique Hispanic cohort disproportionately affected with asthma, prematurity, obesity and other common diseases. Our study confirmed eQTL signals identified in other ethnic groups, while also detecting additional eQTLs unique to our study population. The identified eQTLs will help prioritize findings from future genome-wide association studies in Puerto Ricans.
date: 2015-03-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28492/1/journal.pone.0122464.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28492/3/licence.txt
identifier:   Chen, W and Brehm, JM and Lin, J and Wang, T and Forno, E and Acosta-Pérez, E and Boutaoui, N and Canino, G and Celedón, JC  (2015) Expression Quantitative Trait Loci (eQTL) mapping in Puerto Rican children.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0122464

relation: http://d-scholarship-dev.library.pitt.edu/28494/
title: Bladder uptake of liposomes after intravesical administration occurs by endocytosis
creator: Rajaganapathy, BR
creator: Chancellor, MB
creator: Nirmal, J
creator: Dang, L
creator: Tyagi, P
description: Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM) images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.
date: 2015-03-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28494/1/journal.pone.0122766.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28494/3/licence.txt
identifier:   Rajaganapathy, BR and Chancellor, MB and Nirmal, J and Dang, L and Tyagi, P  (2015) Bladder uptake of liposomes after intravesical administration occurs by endocytosis.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0122766

relation: http://d-scholarship-dev.library.pitt.edu/28493/
title: Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the women's interagency HIV study cohort
creator: Gingo, MR
creator: Zhang, Y
creator: Ghebrehawariat, KB
creator: Jeong, JH
creator: Chu, Y
creator: Yang, Q
creator: Lucht, L
creator: Hanna, DB
creator: Lazar, JM
creator: Gladwin, MT
creator: Morris, A
description: Background: HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women. Design: Prospective cohort study. Methods and Results: We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women's Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3-2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4-5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women. Conclusion: NT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.
date: 2015-03-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28493/1/journal.pone.0123389.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28493/3/licence.txt
identifier:   Gingo, MR and Zhang, Y and Ghebrehawariat, KB and Jeong, JH and Chu, Y and Yang, Q and Lucht, L and Hanna, DB and Lazar, JM and Gladwin, MT and Morris, A  (2015) Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the women's interagency HIV study cohort.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0123389

relation: http://d-scholarship-dev.library.pitt.edu/28495/
title: SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain Acyl-CoA dehydrogenase
creator: Zhang, Y
creator: Bharathi, SS
creator: Rardin, MJ
creator: Uppala, R
creator: Verdin, E
creator: Gibson, BW
creator: Goetzman, ES
description: SIRT3 and SIRT5 have been shown to regulate mitochondrial fatty acid oxidation but the molecular mechanisms behind the regulation are lacking. Here, we demonstrate that SIRT3 and SIRT5 both target human very long-chain acyl-CoA dehydrogenase (VLCAD), a key fatty acid oxidation enzyme. SIRT3 deacetylates and SIRT5 desuccinylates K299 which serves to stabilize the essential FAD cofactor in the active site. Further, we show that VLCAD binds strongly to cardiolipin and isolated mitochondrial membranes via a domain near the C-terminus containing lysines K482, K492, and K507. Acetylation or succinylation of these residues eliminates binding of VLCAD to cardiolipin. SIRT3 deacetylates K507 while SIRT5 desuccinylates K482, K492, and K507. Sirtuin deacylation of recombinant VLCAD rescues membrane binding. Endogenous VLCAD from SIRT3 and SIRT5 knockout mouse liver shows reduced binding to cardiolipin. Thus, SIRT3 and SIRT5 promote fatty acid oxidation by converging upon VLCAD to promote its activity and membrane localization. Regulation of cardiolipin binding by reversible lysine acylation is a novel mechanism that is predicted to extrapolate to other metabolic proteins that localize to the inner mitochondrial membrane.
date: 2015-03-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28495/1/journal.pone.0122297.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28495/3/licence.txt
identifier:   Zhang, Y and Bharathi, SS and Rardin, MJ and Uppala, R and Verdin, E and Gibson, BW and Goetzman, ES  (2015) SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain Acyl-CoA dehydrogenase.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0122297

relation: http://d-scholarship-dev.library.pitt.edu/28496/
title: Serum Biomarkers in Patients with Relapsing Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)
creator: Dejaco, Christian
creator: Oppl, Bastian
creator: Monach, Paul
creator: Cuthbertson, David
creator: Carette, Simon
creator: Hoffman, Gary
creator: Khalidi, Nader
creator: Koening, Curry
creator: Langford, Carol
creator: McKinnon-Maksimowicz, Kathleen
creator: Seo, Philip
creator: Specks, Ulrich
creator: Ytterberg, Steven
creator: Merkel, Peter A.
creator: Zwerina, Jochen
contributor: Kuwana, Masataka
date: 2015-03-26
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28496/1/journal.pone.0121737.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28496/3/licence.txt
identifier:   Dejaco, Christian and Oppl, Bastian and Monach, Paul and Cuthbertson, David and Carette, Simon and Hoffman, Gary and Khalidi, Nader and Koening, Curry and Langford, Carol and McKinnon-Maksimowicz, Kathleen and Seo, Philip and Specks, Ulrich and Ytterberg, Steven and Merkel, Peter A. and Zwerina, Jochen  (2015) Serum Biomarkers in Patients with Relapsing Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss).  PLOS ONE, 10 (3).  e0121737 - e0121737.      
relation: 10.1371/journal.pone.0121737

relation: http://d-scholarship-dev.library.pitt.edu/28497/
title: Elevated levels of mercapturic acids of acrolein and crotonaldehyde in the urine of Chinese women in Singapore who regularly cook at home
creator: Hecht, SS
creator: Koh, WP
creator: Wang, R
creator: Chen, M
creator: Carmella, SG
creator: Murphy, SE
creator: Yuan, JM
description: Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid), crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid), and benzene (S-phenylmercapturic acid), accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090) pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395) pmol/mg creatinine when cooking less than once per week (P for trend 0.018). The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332) and 894 (95% CI, 749-1067) pmol/mg creatinine (P for trend 0.008). We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking.
date: 2015-03-25
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28497/1/journal.pone.0120023.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28497/3/licence.txt
identifier:   Hecht, SS and Koh, WP and Wang, R and Chen, M and Carmella, SG and Murphy, SE and Yuan, JM  (2015) Elevated levels of mercapturic acids of acrolein and crotonaldehyde in the urine of Chinese women in Singapore who regularly cook at home.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120023

relation: http://d-scholarship-dev.library.pitt.edu/29385/
title: Combination of IFNα and poly-I: C reprograms bladder cancer microenvironment for enhanced CTL attraction
creator: Muthuswamy, R
creator: Wang, L
creator: Pitteroff, J
creator: Gingrich, JR
creator: Kalinski, P
description: Background: BCG is a prototypal cancer immunotherapeutic factor currently approved of bladder cancer. In attempt to further enhance the effectiveness of immunotherapy of bladder cancer and, potentially, other malignancies, we evaluated the impact of BCG on local production of chemokines attracting the desirable effector CD8+ T cells (CTLs) and undesirable myeloid-derived suppressor cell (MDSCs) and regulatory T(reg) cells, and the ability of bladder cancer tissues to attract CTLs.Methods: Freshly resected bladder cancer tissues were either analyzed immediately or cultured ex vivo in the absence or presence of the tested factors. The expression of chemokine genes, secretion of chemokines and their local sources in freshly harvested and ex vivo-treated tumor explants were analyzed by quantitative PCR (Taqman), ELISAs and immunofluorescence/confocal microscopy. Migration of CTLs was evaluated ex vivo, using 24-transwell plates. Spearman correlation was used for correlative analysis, while paired Students T test or Wilcoxon was used for statistical analysis of the data.Results: Bladder cancer tissues spontaneously expressed high levels of the granulocyte/MDSC-attractant CXCL8 and Treg-attractant CCL22, but only marginal levels of the CTL-attracting chemokines: CCL5, CXCL9 and CXCL10. Baseline CXCL10 showed strong correlation with local expression of CTL markers. Unexpectedly, BCG selectively induced only the undesirable chemokines, CCL22 and CXCL8, but had only marginal impact on CXCL10 production. In sharp contrast, the combination of IFNα and a TLR3 ligand, poly-I:C (but not the combinations of BCG with IFNα or BCG with poly-I:C), induced high levels of intra-tumoral production of CXCL10 and promoted CTL attraction. The combination of BCG with IFNα + poly-I:C regimen did not show additional advantage.Conclusions: The current data indicate that suboptimal ability of BCG to reprogram cancer-associated chemokine environment may be a factor limiting its therapeutic activity. Our observations that the combination of BCG with (or replacement by) IFNα and poly-I:C allows to reprogram bladder cancer tissues for enhanced CTL entry may provide for new methods of improving the effectiveness of immunotherapy of bladder cancer, helping to extend BCG applications to its more advanced forms, and, potentially, other diseases.
date: 2015-03-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29385/1/art%253A10.1186%252Fs40425-015-0050-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29385/7/licence.txt
identifier:   Muthuswamy, R and Wang, L and Pitteroff, J and Gingrich, JR and Kalinski, P  (2015) Combination of IFNα and poly-I: C reprograms bladder cancer microenvironment for enhanced CTL attraction.  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0050-8

relation: http://d-scholarship-dev.library.pitt.edu/29386/
title: Preamble to the 2015 SITC immunotherapy biomarkers taskforce
creator: Butterfield, LH
creator: Disis, ML
creator: Fox, BA
creator: Khleif, SN
creator: Marincola, FM
description: The Society for Immunotherapy of Cancer (SITC) has regularly hosted workshops and working groups focused on immunologic monitoring and immune biomarkers. Due to advances in cancer immunotherapy, including positive results from clinical trials testing new agents and combinations, emerging new technologies for measuring aspects of immunity, and novel candidate biomarkers from early phase trials, the SITC Immune Biomarkers Taskforce has reconvened to review the state of the art, identify current hurdles to further success and to make recommendations to the field. Topics being addressed by individual working groups include: (1) validation of candidate biomarkers, (2) identification of the most promising technologies, (3) testing of high throughput immune signatures and (4) investigation of the pre-treatment tumor microenvironment. Resultant recommendations will be published in JITC.
date: 2015-03-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29386/1/art%253A10.1186%252Fs40425-015-0052-6.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29386/7/licence.txt
identifier:   Butterfield, LH and Disis, ML and Fox, BA and Khleif, SN and Marincola, FM  (2015) Preamble to the 2015 SITC immunotherapy biomarkers taskforce.  Journal for ImmunoTherapy of Cancer, 3 (1).       
relation: 10.1186/s40425-015-0052-6

relation: http://d-scholarship-dev.library.pitt.edu/28498/
title: Restoration of spermatogenesis and male fertility using an androgen receptor transgene
creator: Walker, WH
creator: Easton, E
creator: Moreci, RS
creator: Toocheck, C
creator: Anamthathmakula, P
creator: Jeyasuria, P
description: Androgens signal through the androgen receptor (AR) to regulate male secondary sexual characteristics, reproductive tract development, prostate function, sperm production, bone and muscle mass as well as body hair growth among other functions. We developed a transgenic mouse model in which endogenous AR expression was replaced by a functionally modified AR transgene. A bacterial artificial chromosome (BAC) was constructed containing all AR exons and introns plus 40 kb each of 5' and 3' regulatory sequence. Insertion of an internal ribosome entry site and the EGFP gene 3' to AR allowed co-expression of AR and EGFP. Pronuclear injection of the BAC resulted in six founder mice that displayed EGFP production in appropriate AR expressing tissues. The six founder mice were mated into a Sertoli cell specific AR knockout (SCARKO) background in which spermatogenesis is blocked at the meiosis stage of germ cell development. The AR-EGFP transgene was expressed in a cyclical manner similar to that of endogenous AR in Sertoli cells and fertility was restored as offspring were produced in the absence of Sertoli cell AR. Thus, the AREGFP transgene under the control of AR regulatory elements is capable of rescuing AR function in a cell selective, AR-null background. These initial studies provide proof of principle that a strategy employing the AR-EGFP transgene can be used to understand AR functions. Transgenic mice expressing selective modifications of the AR-EGFP transgene may provide crucial information needed to elicit the molecular mechanisms by which AR acts in the testis and other androgen responsive tissues.
date: 2015-03-24
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28498/1/journal.pone.0120783.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28498/3/licence.txt
identifier:   Walker, WH and Easton, E and Moreci, RS and Toocheck, C and Anamthathmakula, P and Jeyasuria, P  (2015) Restoration of spermatogenesis and male fertility using an androgen receptor transgene.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120783

relation: http://d-scholarship-dev.library.pitt.edu/28528/
title: Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate
creator: Wolf, ZT
creator: Brand, HA
creator: Shaffer, JR
creator: Leslie, EJ
creator: Arzi, B
creator: Willet, CE
creator: Cox, TC
creator: McHenry, T
creator: Narayan, N
creator: Feingold, E
creator: Wang, X
creator: Sliskovic, S
creator: Karmi, N
creator: Safra, N
creator: Sanchez, C
creator: Deleyiannis, FWB
creator: Murray, JC
creator: Wade, CM
creator: Marazita, ML
creator: Bannasch, DL
description: Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10<sup>-13</sup>; adjusted p= 2.2 x 10<sup>-3</sup>). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 – 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10<sup>-6</sup>) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.
date: 2015-03-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28528/1/journal.pgen.1005059.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28528/3/licence.txt
identifier:   Wolf, ZT and Brand, HA and Shaffer, JR and Leslie, EJ and Arzi, B and Willet, CE and Cox, TC and McHenry, T and Narayan, N and Feingold, E and Wang, X and Sliskovic, S and Karmi, N and Safra, N and Sanchez, C and Deleyiannis, FWB and Murray, JC and Wade, CM and Marazita, ML and Bannasch, DL  (2015) Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate.  PLoS Genetics, 11 (3).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005059

relation: http://d-scholarship-dev.library.pitt.edu/28500/
title: Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs
creator: Kim, SW
creator: Fishilevich, E
creator: Arango-Argoty, G
creator: Lin, Y
creator: Liu, G
creator: Li, Z
creator: Monaghan, AP
creator: Nichols, M
creator: John, B
description: Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer.
date: 2015-03-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28500/1/journal.pone.0120296.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28500/3/licence.txt
identifier:   Kim, SW and Fishilevich, E and Arango-Argoty, G and Lin, Y and Liu, G and Li, Z and Monaghan, AP and Nichols, M and John, B  (2015) Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120296

relation: http://d-scholarship-dev.library.pitt.edu/28499/
title: Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery
creator: Gocze, I
creator: Koch, M
creator: Renner, P
creator: Zeman, F
creator: Graf, BM
creator: Dahlke, MH
creator: Nerlich, M
creator: Schlitt, HJ
creator: Kellum, JA
creator: Bein, T
description: Objective To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients. Introduction Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function. Methods In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test. Results 107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l2/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001). Conclusions Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major noncardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.
date: 2015-03-23
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28499/1/journal.pone.0120863.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28499/3/licence.txt
identifier:   Gocze, I and Koch, M and Renner, P and Zeman, F and Graf, BM and Dahlke, MH and Nerlich, M and Schlitt, HJ and Kellum, JA and Bein, T  (2015) Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120863

relation: http://d-scholarship-dev.library.pitt.edu/24158/
title: Association between free testosterone levels and anal human papillomavirus Types 16/18 infections in a cohort of men who have sex with men
creator: Hsu, HK
creator: Brown, TT
creator: Li, X
creator: Young, S
creator: Cranston, RD
creator: D'Souza, G
creator: Jacobson, LP
creator: Martínez-Maza, O
creator: Seaberg, EC
creator: Margolick, JB
creator: Jenkins, FJ
creator: Moran, MG
creator: Chua, K
creator: Bolan, RK
creator: Detels, R
creator: Wiley, DJ
description: Background Human papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown. Methods Free testosterone (FT) was measured in serum from 340 Multicenter AIDS Cohort Study (MACS) participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing. Results Participants were, on average, 60 (+5.4) years of age, White (86%), and HIV-uninfected (56%); Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence= 17.1%, HPV18=9.1%). In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24) higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37) higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing) were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/ 18 infection in unadjusted and adjusted analyses. Conclusions Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years later, independent of sexual behavior and other potential confounders. The mechanisms underlying this association remain unclear and warrant further study.
date: 2015-03-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24158/1/journal.pone.0119447_%281%29.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24158/4/licence.txt
identifier:   Hsu, HK and Brown, TT and Li, X and Young, S and Cranston, RD and D'Souza, G and Jacobson, LP and Martínez-Maza, O and Seaberg, EC and Margolick, JB and Jenkins, FJ and Moran, MG and Chua, K and Bolan, RK and Detels, R and Wiley, DJ  (2015) Association between free testosterone levels and anal human papillomavirus Types 16/18 infections in a cohort of men who have sex with men.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0119447

relation: http://d-scholarship-dev.library.pitt.edu/29387/
title: An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2
creator: Mancini, C
creator: Orsi, L
creator: Guo, Y
creator: Li, J
creator: Chen, Y
creator: Wang, F
creator: Tian, L
creator: Liu, X
creator: Zhang, J
creator: Jiang, H
creator: Nmezi, BS
creator: Tatsuta, T
creator: Giorgio, E
creator: Di Gregorio, E
creator: Cavalieri, S
creator: Pozzi, E
creator: Mortara, P
creator: Caglio, MM
creator: Balducci, A
creator: Pinessi, L
creator: Langer, T
creator: Padiath, QS
creator: Hakonarson, H
creator: Zhang, X
creator: Brusco, A
description: Background: Hereditary ataxias are a heterogeneous group of neurodegenerative disorders, where exome sequencing may become an important diagnostic tool to solve clinically or genetically complex cases. Methods: We describe an Italian family in which three sisters were affected by ataxia with postural/intentional myoclonus and involuntary movements at onset, which persisted during the disease. Oculomotor apraxia was absent. Clinical and genetic data did not allow us to exclude autosomal dominant or recessive inheritance and suggest a disease gene. Results: Exome sequencing identified a homozygous c.6292C>T (p.Arg2098*) mutation in SETX and a heterozygous c.346G>A (p.Gly116Arg) mutation in AFG3L2 shared by all three affected individuals. A fourth sister (II.7) had subclinical myoclonic jerks at proximal upper limbs and perioral district, confirmed by electrophysiology, and carried the p.Gly116Arg change. Three siblings were healthy. Conclusions: Exome sequencing is a powerful tool in identifying disease genes. We identified an atypical form of Ataxia with Oculoapraxia type 2 (AOA2) with myoclonus at onset associated with the c.6292C>T (p.Arg2098*) homozygous mutation. Because the same genotype was described in six cases from a Tunisian family with a typical AOA2 without myoclonus, we speculate this latter feature is associated with a second mutated gene, namely AFG3L2 (p.Gly116Arg variant).
date: 2015-03-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29387/1/art%253A10.1186%252Fs12881-015-0159-0.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29387/7/licence.txt
identifier:   Mancini, C and Orsi, L and Guo, Y and Li, J and Chen, Y and Wang, F and Tian, L and Liu, X and Zhang, J and Jiang, H and Nmezi, BS and Tatsuta, T and Giorgio, E and Di Gregorio, E and Cavalieri, S and Pozzi, E and Mortara, P and Caglio, MM and Balducci, A and Pinessi, L and Langer, T and Padiath, QS and Hakonarson, H and Zhang, X and Brusco, A  (2015) An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2.  BMC Medical Genetics, 16 (1).       
relation: 10.1186/s12881-015-0159-0

relation: http://d-scholarship-dev.library.pitt.edu/25576/
title: Bridging the Data Talent Gap: Positioning the iSchool as an Agent for Change
creator: Lyon, Liz
creator: Brenner, Aaron
description: <jats:p>This paper examines the role, functions and value of the “iSchool” as an agent of change in the data informatics and data curation arena. A brief background to the iSchool movement is given followed by a brief review of the data decade, which highlights key data trends from the iSchool perspective: open data and open science, big data and disciplinary data diversity. The growing emphasis on the shortage of data talent is noted and a family of data science roles identified. The paper moves on to describe three primary functions of iSchools: education, research intelligence and professional practice, which form the foundations of a new Capability Ramp Model. The model is illustrated by mini-case studies from the School of Information Sciences, University of Pittsburgh: the immersive (laboratory-based) component of two new Research Data Management and Research Data Infrastructures graduate courses, a new practice partnership with the University Library System centred on RDM, and the mapping of disciplinary data practice using the Community Capability Model Profile Tool. The paper closes with a look to the future and, based on the assertion that data is mission-critical for iSchools, some steps are proposed for the next data decade: moving data education programs into the mainstream core curriculum, adopting a translational data science perspective and strengthening engagement with the Research Data Alliance.</jats:p>
publisher: Edinburgh University Library
date: 2015-03-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25576/2/349-1481-1-PB.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25576/5/licence.txt
identifier:   Lyon, Liz and Brenner, Aaron  (2015) Bridging the Data Talent Gap: Positioning the iSchool as an Agent for Change.  International Journal of Digital Curation, 10 (1).  111 - 122.      
relation: 10.2218/ijdc.v10i1.349

relation: http://d-scholarship-dev.library.pitt.edu/29391/
title: Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial
creator: Koren, G
creator: Clark, S
creator: Hankins, GDV
creator: Caritis, SN
creator: Umans, JG
creator: Miodovnik, M
creator: Mattison, DR
creator: Matok, I
description: Background: Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo. Methods: We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2-4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing. Results: Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. Conclusions: Doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy. Trial Registration: Clinical Trial Registration No: NCT00614445.
date: 2015-03-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29391/1/art%253A10.1186%252Fs12884-015-0488-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29391/7/licence.txt
identifier:   Koren, G and Clark, S and Hankins, GDV and Caritis, SN and Umans, JG and Miodovnik, M and Mattison, DR and Matok, I  (2015) Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial.  BMC Pregnancy and Childbirth, 15 (1).       
relation: 10.1186/s12884-015-0488-1

relation: http://d-scholarship-dev.library.pitt.edu/24157/
title: Phosphorescence monitoring of hypoxic microenvironment in solid-tumors to evaluate chemotherapeutic effects using the hypoxia-sensitive iridium (III) coordination compound
creator: Zeng, Y
creator: Liu, Y
creator: Shang, J
creator: Ma, J
creator: Wang, R
creator: Deng, L
creator: Guo, Y
creator: Zhong, F
creator: Bai, M
creator: Zhang, S
creator: Wu, D
description: Objectives: To utilize phosphorescence to monitor hypoxic microenvironment in solid-tumors and investigate cancer chemotherapeutic effects in vivo. Methods: A hypoxia-sensitive probe named BTP was used to monitor hypoxic microenvironment in solid-tumors. The low-dose metronomic treatment with cisplatin was used in anti-angiogenetic chemotherapeutic programs. The phosphorescence properties of BTP were detected by a spectrofluorometer. BTP cytotoxicity utilized cell necrosis and apoptosis, which were evaluated by trypan blue dye exclusion and Hoechst33342 plus propidium iodide assays. Tumor-bearing mouse models of colon adenocarcinoma were used for tumor imaging in vivo. Monitoring of the hypoxic microenvironment in tumors was performed with a Maestro 2 fluorescence imaging system. Tumor tissues in each group were harvested regularly and treated with pathological hematoxylin and eosin and immunohistochemical staining to confirm imaging results. Results: BTP did not feature obvious cytotoxicity for cells, and tumor growth in low-dose metronomic cisplatin treated mice was significantly inhibited by chemotherapy. Hypoxic levels significantly increased due to cisplatin, as proven by the expression level of related proteins. Phosphorescence intensity in the tumors of mice in the cisplatin group was stronger and showed higher contrast than that in tumors of saline treated mice. Conclusions: We develop a useful phosphorescence method to evaluate the chemotherapeutic effects of cisplatin. The proposed method shows potential as a phosphorescence imaging approach for evaluating chemotherapeutic effects in vivo , especially anti-angiogenesis.
date: 2015-03-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24157/1/journal.pone.0121293.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24157/4/licence.txt
identifier:   Zeng, Y and Liu, Y and Shang, J and Ma, J and Wang, R and Deng, L and Guo, Y and Zhong, F and Bai, M and Zhang, S and Wu, D  (2015) Phosphorescence monitoring of hypoxic microenvironment in solid-tumors to evaluate chemotherapeutic effects using the hypoxia-sensitive iridium (III) coordination compound.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0121293

relation: http://d-scholarship-dev.library.pitt.edu/24132/
title: Science Classroom Inquiry (SCI) simulations: A novel method to scaffold science learning
creator: Peffer, ME
creator: Beckler, ML
creator: Schunn, C
creator: Renken, M
creator: Revak, A
description: Science education is progressively more focused on employing inquiry-based learning methods in the classroom and increasing scientific literacy among students. However, due to time and resource constraints, many classroom science activities and laboratory experiments focus on simple inquiry, with a step-by-step approach to reach predetermined outcomes. The science classroom inquiry (SCI) simulations were designed to give students real life, authentic science experiences within the confines of a typical classroom. The SCI simulations allow students to engage with a science problem in a meaningful, inquiry-based manner. Three discrete SCI simulations were created as website applications for use with middle school and high school students. For each simulation, students were tasked with solving a scientific problem through investigation and hypothesis testing. After completion of the simulation, 67% of students reported a change in how they perceived authentic science practices, specifically related to the complex and dynamic nature of scientific research and how scientists approach problems. Moreover, 80% of the students who did not report a change in how they viewed the practice of science indicated that the simulation confirmed or strengthened their prior understanding. Additionally, we found a statistically significant positive correlation between students' self-reported changes in understanding of authentic science practices and the degree to which each simulation benefitted learning. Since SCI simulations were effective in promoting both student learning and student understanding of authentic science practices with both middle and high school students, we propose that SCI simulations are a valuable and versatile technology that can be used to educate and inspire a wide range of science students on the real-world complexities inherent in scientific study.
date: 2015-03-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24132/1/journal.pone.0120638.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24132/4/licence.txt
identifier:   Peffer, ME and Beckler, ML and Schunn, C and Renken, M and Revak, A  (2015) Science Classroom Inquiry (SCI) simulations: A novel method to scaffold science learning.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0120638

relation: http://d-scholarship-dev.library.pitt.edu/24156/
title: The receptor for advanced glycation end products (RAGE) contributes to the progression of emphysema in mice
creator: Sambamurthy, N
creator: Leme, AS
creator: Oury, TD
creator: Shapiro, SD
description: Several recent clinical studies have implied a role for the receptor for advanced glycation end products (RAGE) and its variants in chronic obstructive pulmonary disease (COPD). In this study we have defined a role for RAGE in the pathogenesis of emphysema in mice. RAGE deficient mice (RAGE-/-) exposed to chronic cigarette smoke were significantly protected from smoke induced emphysema as determined by airspace enlargement and had no significant reduction in lung tissue elastance when compared to their air exposed controls contrary to their wild type littermates. The progression of emphysema has been largely attributed to an increased inflammatory cell-mediated elastolysis. Acute cigarette smoke exposure in RAGE-/- mice revealed an impaired early recruitment of neutrophils, approximately a 6-fold decrease compared to wild type mice. Hence, impaired neutrophil recruitment with continued cigarette smoke exposure reduces elastolysis and consequent emphysema.
date: 2015-03-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24156/1/journal.pone.0118979.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24156/4/licence.txt
identifier:   Sambamurthy, N and Leme, AS and Oury, TD and Shapiro, SD  (2015) The receptor for advanced glycation end products (RAGE) contributes to the progression of emphysema in mice.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0118979

relation: http://d-scholarship-dev.library.pitt.edu/24103/
title: Glycated hemoglobin and incident type 2 diabetes in singaporean Chinese adults: The Singapore Chinese Health Study
creator: Bancks, MP
creator: Odegaard, AO
creator: Koh, WP
creator: Yuan, JM
creator: Gross, MD
creator: Pereira, MA
description: Background: The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes. Methods: Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and had no cancer and no reported history of diabetes or cardiovascular disease events. Diabetes was defined as self-report of physician diagnosis, identified at the follow-up II visit (2006-2010). Results: Hazard ratios (and 95%confidence intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox regression models and continuous HbA1c with cubic spline analysis. Compared to individuals with an HbA1c ≤ 5.7% (≤39 mmol/mol), individuals with HbA1c 5.8-5.9% (40-41 mmol/mol), 6.0-6.1% (42-43 mmol/mol), 6.2-6.4% (44-47 mmol/mol), and ≥ 6.5% (≥48 mmol/mol) had significantly increased risk for incident diabetes during followup. In cubic spline analysis, levels below 5.7% HbA1c were not significantly associated with incident diabetes. Conclusions: Our study found a strong and graded association with HbA1c 5.8% and above with incident diabetes in Chinese men and women.
date: 2015-03-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24103/1/journal.pone.0119884.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24103/4/licence.txt
identifier:   Bancks, MP and Odegaard, AO and Koh, WP and Yuan, JM and Gross, MD and Pereira, MA  (2015) Glycated hemoglobin and incident type 2 diabetes in singaporean Chinese adults: The Singapore Chinese Health Study.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0119884

relation: http://d-scholarship-dev.library.pitt.edu/24104/
title: Multiple proteases to localize oxidation sites
creator: Gu, L
creator: Robinson, RAS
description: Proteins present in cellular environments with high levels of reactive oxygen and nitrogen species and/or low levels of antioxidants are highly susceptible to oxidative post-translational modification (PTM). Irreversible oxidative PTMs can generate a complex distribution of modified protein molecules, recently termed as proteoforms. Using ubiquitin as a model system, we mapped oxidative modification sites using trypsin, Lys-C, and Glu-C peptides. Several M+16 Da proteoforms were detected as well as proteoforms that include other previously unidentified oxidative modifications. This work highlights the use of multiple protease digestions to give insights to the complexity of oxidative modifications possible in bottom-up analyses.
date: 2015-03-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24104/1/journal.pone.0116606.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24104/4/licence.txt
identifier:   Gu, L and Robinson, RAS  (2015) Multiple proteases to localize oxidation sites.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0116606

relation: http://d-scholarship-dev.library.pitt.edu/22265/
title: Telerehabilitation: Policy Issues and Research Tools
creator: Seelman, Katherine D
creator: Hartman, Linda M
description: <jats:p>A number of experts recognize the importance of public policy as a complementary framework for telehealth, telemedicine, and by association, telerehabilitation. The purpose of this paper is to report on the current state-of-the-science on telerehabilitation (TR) policy and research methodology and make recommendations about future research needs. We conducted an extensive search of the literature via search terms grouped into the main topics of telerehabilitation, policy, population of users, and policy specific issues such as cost and reimbursement.The availability of rigorous and valid evidence-based cost studies emerged as a major challenge to the field. Existing cost studies provide evidence that tele-homecare may be a promising application area for TR. Cost studies also indicate that tele-psychiatry is a promising telepractice area. Notably, the literature did not reference the International Classification on Functioning, Disability and Health (ICF).We concluded that outcome studies characterized by rigorous and comprehensive TR assessment and evaluation are required to generate confidence among providers, payers, clinicians, and end users. Study criteria must comprehensively assess consumer satisfaction and participation via medical, functional, and quality of life items such as assistive technology and environmental factors.</jats:p>
publisher: University Library System, University of Pittsburgh
date: 2015-03-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22265/1/704-2921-1-PB-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22265/8/licence.txt
identifier:   Seelman, Katherine D and Hartman, Linda M  (2015) Telerehabilitation: Policy Issues and Research Tools.  International Journal of Telerehabilitation.  37 - 48.      
relation: 10.5195/ijt.2008.704

relation: http://d-scholarship-dev.library.pitt.edu/32686/
title: New method for the orthogonal labeling and purification of Toxoplasma gondii proteins while inside the host cell
creator: Wier, GM
creator: McGreevy, EM
creator: Brown, MJ
creator: Boyle, JP
description: oxoplasma gondii is an obligate intracellular protozoan parasite that is capable of causing severe disease in immunocompromised humans. How T. gondii is able to modulate the host cell to support itself is still poorly understood. Knowledge pertaining to the host-parasite interaction could be bolstered by developing a system to specifically label parasite proteins while the parasite grows inside the host cell. For this purpose, we have created a strain of T. gondii that expresses a mutant Escherichia coli methionyl-tRNA synthetase (MetRS<sup>NLL</sup>) that allows methionine tRNA to be loaded with the azide-containing methionine analog azidonorleucine (Anl). Anl-containing proteins are susceptible to a copper-catalyzed “click” reaction to attach affinity tags for purification or fluorescent tags for visualization. The MetRS<sup>NLL</sup>-Anl system labels nascent T. gondii proteins in an orthogonal fashion, labeling proteins only in MetRS<sup>NLL</sup>-expressing parasites. This system should be useful for nonradioactive pulse-chase studies and purification of nascently translated proteins. Although this approach allows labeling of a diverse array of parasite proteins, secreted parasite proteins appear to be only minimally labeled in MetRS<sup>NLL</sup>-expressing T. gondii. The minimal labeling of secreted proteins is likely a consequence of the selective charging of the initiator tRNA (and not the elongator methionine tRNA) by the heterologously expressed bacterial MetRS. IMPORTANCE Studying how T. gondii modifies the host cell to permit its survival is complicated by the complex protein environment of the host cell. The approach presented in this article provides the first method for specific labeling of T. gondii proteins while the parasite grows inside the host cell. We show that this approach is useful for pulse-chase labeling of parasite proteins during in vitro growth. It should also be applicable during in vivo infections and in other apicomplexan parasites, including Plasmodium spp.
date: 2015-03-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32686/1/mBio-2015-Wier.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32686/7/licence.txt
identifier:   Wier, GM and McGreevy, EM and Brown, MJ and Boyle, JP  (2015) New method for the orthogonal labeling and purification of Toxoplasma gondii proteins while inside the host cell.  mBio, 6 (2).   ISSN 2161-2129     
relation: 10.1128/mBio.01628-14

relation: http://d-scholarship-dev.library.pitt.edu/24102/
title: Distinct human stem cell populations in small and large intestine
creator: Cramer, JM
creator: Thompson, T
creator: Geskin, A
creator: Laframboise, W
creator: Lagasse, E
description: The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2.We utilized flow cytometry, fluorescence-activated cell sorting, gene expression analysis and a three-dimensional in vitro differentiation assay to characterize their stemcell properties. We identified stem cell markers that separate subpopulations of colony-forming cells in the small and large intestine and revealed important differences in differentiation, proliferation and disease pathways using gene expression analysis. Single cells from small and large intestine cultures formed organoids that reflect the distinct cellular hierarchy found in vivo and respond differently to identical exogenous cues. Our characterization identified numerous differences between small and large intestine epithelial stem cells suggesting possible connections to intestinal disease.
date: 2015-03-09
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24102/1/journal.pone.0118792.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24102/4/licence.txt
identifier:   Cramer, JM and Thompson, T and Geskin, A and Laframboise, W and Lagasse, E  (2015) Distinct human stem cell populations in small and large intestine.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0118792

relation: http://d-scholarship-dev.library.pitt.edu/29395/
title: Effect of plasmid replication deregulation via inc mutations on E. coli proteome &amp; simple flux model analysis
creator: Meade, J
creator: Bartlow, P
creator: Trivedi, RN
creator: Akhtar, P
creator: Ataai, MM
creator: Khan, SA
creator: Domach, MM
description: When the replication of a plasmid based on sucrose selection is deregulated via the inc1 and inc2 mutations, high copy numbers (7,000 or greater) are attained while the growth rate on minimal medium is negligibly affected. Adaptions were assumed to be required in order to sustain the growth rate. Proteomics indicated that indeed a number of adaptations occurred that included increased expression of ribosomal proteins and 2-oxoglutarate dehydrogenase. The operating space prescribed by a basic flux model that maintained phenotypic traits (e.g. growth, byproducts, etc.) within typical bounds of resolution was consistent with the flux implications of the proteomic changes.
date: 2015-03-08
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29395/1/art%253A10.1186%252Fs12934-015-0212-x.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29395/7/licence.txt
identifier:   Meade, J and Bartlow, P and Trivedi, RN and Akhtar, P and Ataai, MM and Khan, SA and Domach, MM  (2015) Effect of plasmid replication deregulation via inc mutations on E. coli proteome &amp; simple flux model analysis.  Microbial Cell Factories, 14 (1).       
relation: 10.1186/s12934-015-0212-x

relation: http://d-scholarship-dev.library.pitt.edu/24101/
title: P21<sup>WAF1/CIP1</sup> RNA expression in highly HIV-1 exposed, uninfected individuals
creator: Herbeck, J
creator: Ghorai, S
creator: Chen, L
creator: Rinaldo, CR
creator: Margolick, JB
creator: Detels, R
creator: Jacobson, L
creator: Wolinsky, S
creator: Mullins, JI
description: Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21WAF1/CIP1 (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R2 = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1.
date: 2015-03-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24101/1/journal.pone.0119218.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24101/4/licence.txt
identifier:   Herbeck, J and Ghorai, S and Chen, L and Rinaldo, CR and Margolick, JB and Detels, R and Jacobson, L and Wolinsky, S and Mullins, JI  (2015) P21<sup>WAF1/CIP1</sup> RNA expression in highly HIV-1 exposed, uninfected individuals.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0119218

relation: http://d-scholarship-dev.library.pitt.edu/24100/
title: SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor Growth in Vivo by inducing G2/M cell cycle arrest
creator: Tandon, M
creator: Salamoun, JM
creator: Carder, EJ
creator: Farber, E
creator: Xu, S
creator: Deng, F
creator: Tang, H
creator: Wipf, P
creator: Wang, QJ
description: Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment.
date: 2015-03-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24100/1/journal.pone.0119346.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24100/4/licence.txt
identifier:   Tandon, M and Salamoun, JM and Carder, EJ and Farber, E and Xu, S and Deng, F and Tang, H and Wipf, P and Wang, QJ  (2015) SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor Growth in Vivo by inducing G2/M cell cycle arrest.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0119346

relation: http://d-scholarship-dev.library.pitt.edu/24099/
title: Comparative genomics of Cluster O mycobacteriophages
creator: Cresawn, SG
creator: Pope, WH
creator: Jacobs-Sera, D
creator: Bowman, CA
creator: Russell, DA
creator: Dedrick, RM
creator: Adair, T
creator: Anders, KR
creator: Ball, S
creator: Bollivar, D
creator: Breitenberger, C
creator: Burnett, SH
creator: Butela, K
creator: Byrnes, D
creator: Carzo, S
creator: Cornely, KA
creator: Cross, T
creator: Daniels, RL
creator: Dunbar, D
creator: Findley, AM
creator: Gissendanner, CR
creator: Golebiewska, UP
creator: Hartzog, GA
creator: Hatherill, JR
creator: Hughes, LE
creator: Jalloh, CS
creator: De Los Santos, C
creator: Ekanem, K
creator: Khambule, SL
creator: King, RA
creator: King-Smith, C
creator: Klyczek, K
creator: Krukonis, GP
creator: Laing, C
creator: Lapin, JS
creator: Lopez, AJ
creator: Mkhwanazi, SM
creator: Molloy, SD
creator: Moran, D
creator: Munsamy, V
creator: Pacey, E
creator: Plymale, R
creator: Poxleitner, M
creator: Reyna, N
creator: Schildbach, JF
creator: Stukey, J
creator: Taylor, SE
creator: Ware, VC
creator: Wellmann, AL
creator: Westholm, D
creator: Wodarski, D
creator: Zajko, M
creator: Zikalala, TS
creator: Hendrix, RW
creator: Hatfull, GF
description: Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.
date: 2015-03-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24099/1/journal.pone.0118725.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24099/4/licence.txt
identifier:   Cresawn, SG and Pope, WH and Jacobs-Sera, D and Bowman, CA and Russell, DA and Dedrick, RM and Adair, T and Anders, KR and Ball, S and Bollivar, D and Breitenberger, C and Burnett, SH and Butela, K and Byrnes, D and Carzo, S and Cornely, KA and Cross, T and Daniels, RL and Dunbar, D and Findley, AM and Gissendanner, CR and Golebiewska, UP and Hartzog, GA and Hatherill, JR and Hughes, LE and Jalloh, CS and De Los Santos, C and Ekanem, K and Khambule, SL and King, RA and King-Smith, C and Klyczek, K and Krukonis, GP and Laing, C and Lapin, JS and Lopez, AJ and Mkhwanazi, SM and Molloy, SD and Moran, D and Munsamy, V and Pacey, E and Plymale, R and Poxleitner, M and Reyna, N and Schildbach, JF and Stukey, J and Taylor, SE and Ware, VC and Wellmann, AL and Westholm, D and Wodarski, D and Zajko, M and Zikalala, TS and Hendrix, RW and Hatfull, GF  (2015) Comparative genomics of Cluster O mycobacteriophages.  PLoS ONE, 10 (3).       
relation: 10.1371/journal.pone.0118725

relation: http://d-scholarship-dev.library.pitt.edu/22051/
title: Attack-resilient mix-zones over road networks: Architecture and algorithms
creator: Palanisamy, B
creator: Liu, L
description: Continuous exposure of location information, even with spatially cloaked resolution, may lead to breaches of location privacy due to statistics-based inference attacks. An alternative and complementary approach to spatial cloaking based location anonymization is to break the continuity of location exposure by introducing techniques, such as mix-zones, where no application can trace user movements. Several factors impact on the effectiveness of mix-zone approach, such as user population, mix-zone geometry, location sensing rate and spatial resolution, as well as spatial and temporal constraints on user movement patterns. However, most of the existing mix-zone proposals fail to provide effective mix-zone construction and placement algorithms that are resilient to timing and transition attacks. This paper presents MobiMix, a road network based mix-zone framework to protect location privacy of mobile users traveling on road networks. It makes three original contributions. First, we provide the formal analysis on the vulnerabilities of directly applying theoretical rectangle mix-zones to road networks in terms of anonymization effectiveness and resilience to timing and transition attacks. Second, we develop a suite of road network mix-zone construction methods that effectively consider the above mentioned factors to provide higher level of resilience to timing and transition attacks, and yield a specified lower-bound on the level of anonymity. Third, we present a set of mix-zone placement algorithms that identify the best set of road intersections for mix-zone placement considering the road network topology, user mobility patterns and road characteristics. We evaluate the MobiMix approach through extensive experiments conducted on traces produced by GTMobiSim on different scales of geographic maps. Our experiments show that MobiMix offers high level of anonymity and high level of resilience to timing and transition attacks, compared to existing mix-zone approaches.
date: 2015-03-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22051/1/RoadNetMixzones-TMC-2014.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22051/8/licence.txt
identifier:   Palanisamy, B and Liu, L  (2015) Attack-resilient mix-zones over road networks: Architecture and algorithms.  IEEE Transactions on Mobile Computing, 14 (3).  495 - 508.  ISSN 1536-1233     
relation: 10.1109/TMC.2014.2321747

relation: http://d-scholarship-dev.library.pitt.edu/21847/
title: Critical Design Elements of E-Health Applications for Users with Severe Mental Illness: Singular Focus, Simple Architecture, Prominent Contents, Explicit Navigation, and Inclusive Hyperlinks
creator: Rotondi, AJ
creator: Eack, SM
creator: Hanusa, BH
creator: Spring, MB
creator: Haas, GL
description: Objective: E-health applications are becoming integral components of general medical care delivery models and emerging for mental health care. Few exist for treatment of those with severe mental illness (SMI). In part, this is due to a lack of models to design such technologies for persons with cognitive impairments and lower technology experience. This study evaluated the effectiveness of an e-health design model for persons with SMI termed the Flat Explicit Design Model (FEDM). Methods: Persons with schizophrenia (n = 38) performed tasks to evaluate the effectiveness of 5 Web site designs: 4 were prominent public Web sites, and 1 was designed according to the FEDM. Linear mixed-effects regression models were used to examine differences in usability between the Web sites. Omnibus tests of between-site differences were conducted, followed by post hoc pairwise comparisons of means to examine specific Web site differences when omnibus tests reached statistical significance. Results: The Web site designed using the FEDM required less time to find information, had a higher success rate, and was rated easier to use and less frustrating than the other Web sites. The home page design of one of the other Web sites provided the best indication to users about a Web site's contents. The results are consistent with and were used to expand the FEDM. Conclusions: The FEDM provides evidence-based guidelines to design e-health applications for person with SMI, including: minimize an application's layers or hierarchy, use explicit text, employ navigational memory aids, group hyperlinks in 1 area, and minimize the number of disparate subjects an application addresses.
date: 2015-03-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/21847/1/licence.txt
identifier:   Rotondi, AJ and Eack, SM and Hanusa, BH and Spring, MB and Haas, GL  (2015) Critical Design Elements of E-Health Applications for Users with Severe Mental Illness: Singular Focus, Simple Architecture, Prominent Contents, Explicit Navigation, and Inclusive Hyperlinks.  Schizophrenia Bulletin, 41 (2).  440 - 448.  ISSN 0586-7614     
relation: 10.1093/schbul/sbt194

relation: http://d-scholarship-dev.library.pitt.edu/23699/
title: How cells became records: standardization and infrastructure in tissue culture
creator: Acker, A
description: This article follows the history of tissue culture through its standardization as a technology, instrument, and ubiquitous object of reference for scientists working with cells. It identifies how human cells are established as cell lines and become records. As information infrastructure, cell lines have consequences for key archival concepts that rely on narratives of origin, bodies, and recorded information. The article contributes to a theory of the record by looking at cells in functional contexts of tissue culture, from the establishment of reference lines to the identification of cross-culture contamination, to their storage and dissemination. It puts forth a theory of the biorecord by examining acts of formalization in the standardization of scientific recordkeeping in biotechnology. The paper speaks to archival studies of scientific recordkeeping and argues for an expansion of research that examines nonprototypical records in functional contexts of creation, use, and processes of standardization.
date: 2015-03-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/23699/1/licence.txt
identifier:   Acker, A  (2015) How cells became records: standardization and infrastructure in tissue culture.  Archival Science, 15 (1).  1 - 24.  ISSN 1389-0166     
relation: 10.1007/s10502-013-9213-x

relation: http://d-scholarship-dev.library.pitt.edu/23994/
title: Portrayal of alcohol intoxication on youtube
creator: Primack, BA
creator: Colditz, JB
creator: Pang, KC
creator: Jackson, KM
description: Background: We aimed to characterize the content of leading YouTube videos related to alcohol intoxication and to examine factors associated with alcohol intoxication in videos that were assessed positively by viewers. Methods: We systematically captured the 70 most relevant and popular videos on YouTube related to alcohol intoxication. We employed an iterative process to codebook development which resulted in 42 codes in 6 categories: video characteristics, character socio demographics, alcohol depiction, degree of alcohol use, characteristics associated with alcohol, and consequences of alcohol. Results: There were a total of 333,246,875 views for all videos combined. While 89% of videos involved males, only 49% involved females. The videos had a median of 1,646 (interquartile range [IQR] 300 to 22,969) "like" designations and 33 (IQR 14 to 1,261) "dislike" designations each. Liquor was most frequently represented, followed by beer and then wine/champagne. Nearly one-half (44%) of videos contained a brand reference. Humor was juxtaposed with alcohol use in 79% of videos, and motor vehicle use was present in 24%. There were significantly more likes per dislike, indicating more positive sentiment, when there was representation of liquor (29.1 vs. 11.4, p = 0.008), brand references (32.1 vs. 19.2, p = 0.04), and/or physical attractiveness (67.5 vs. 17.8, p < 0.001). Conclusions: Internet videos depicting alcohol intoxication are heavily viewed. Nearly, half of these videos involve a brand-name reference. While these videos commonly juxtapose alcohol intoxication with characteristics such as humor and attractiveness, they infrequently depict negative clinical outcomes. The popularity of this site may provide an opportunity for public health intervention.
date: 2015-03-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/23994/1/licence.txt
identifier:   Primack, BA and Colditz, JB and Pang, KC and Jackson, KM  (2015) Portrayal of alcohol intoxication on youtube.  Alcoholism: Clinical and Experimental Research, 39 (3).  496 - 503.  ISSN 0145-6008     
relation: 10.1111/acer.12640

relation: http://d-scholarship-dev.library.pitt.edu/24175/
title: Defending the global knowledge commons
creator: Smith, Jackie
description: Members are encouraged to use creative commons licensing and to join others in a pledge to be open by agreeing to review for and publish in mainly if not solely open access journals.
date: 2015-03
type: Article
type: NonPeerReviewed
format: other
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24175/1/
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24175/2/opendemocracy.net-Defending_the_global_knowledge_commons.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24175/5/licence.txt
identifier:   Smith, Jackie  (2015) Defending the global knowledge commons.         
relation: https://opendemocracy.net/jackie-smith/defending-global-knowledge-commons

relation: http://d-scholarship-dev.library.pitt.edu/29405/
title: Renal angina: Concept and development of pretest probability assessment in acute kidney injury
creator: Chawla, LS
creator: Goldstein, SL
creator: Kellum, JA
creator: Ronco, C
description: The context of a diagnostic test is a critical component for the interpretation of its result. This context defines the pretest probability of the diagnosis and forms the basis for the interpretation and value of adding the diagnostic test. In the field of acute kidney injury, a multitude of early diagnostic biomarkers have been developed, but utilization in the appropriate context is less well understood and has not been codified until recently. In order to better operationalize the context and pretest probability assessment for acute kidney injury diagnosis, the renal angina concept was proposed in 2010 for use in both children and adults. Renal angina has been assessed in approximately 1,000 subjects. However, renal angina as a concept is still unfamiliar to most clinicians and the rationale for introducing the term is not obvious. We therefore review the concept and development of renal angina, and the currently available data validating it. We discuss the various arguments for and against this construct. Future research testing the performance of renal angina with acute kidney injury biomarkers is warranted.
date: 2015-02-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29405/1/art%253A10.1186%252Fs13054-015-0779-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29405/7/licence.txt
identifier:   Chawla, LS and Goldstein, SL and Kellum, JA and Ronco, C  (2015) Renal angina: Concept and development of pretest probability assessment in acute kidney injury.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-015-0779-y

relation: http://d-scholarship-dev.library.pitt.edu/24098/
title: Study of integrated heterogeneous data reveals prognostic power of gene expression for breast cancer survival
creator: Neapolitan, RE
creator: Jiang, X
description: Background: Studies show that thousands of genes are associated with prognosis of breast cancer. Towards utilizing available genetic data, efforts have been made to predict outcomes using gene expression data, and a number of commercial products have been developed. These products have the following shortcomings: 1) They use the Cox model for prediction. However, the RSF model has been shown to significantly outperform the Cox model. 2) Testing was not done to see if a complete set of clinical predictors could predict as well as the gene expression signatures. Methodology/Findings: We address these shortcomings. The METABRIC data set concerns 1981 breast cancer tumors. Features include 21 clinical features, expression levels for 16,384 genes, and survival. We compare the survival prediction performance of the Cox model and the RSF model using the clinical data and the gene expression data to their performance using only the clinical data. We obtain significantly better results when we used both clinical data and gene expression data for 5 year, 10 year, and 15 year survival prediction. When we replace the gene expression data by PAM50 subtype, our results are significant only for 5 year and 15 year prediction. We obtain significantly better results using the RSF model over the Cox model. Finally, our results indicate that gene expression data alone may predict longterm survival. Conclusions/Significance: Our results indicate that we can obtain improved survival prediction using clinical data and gene expression data compared to prediction using only clinical data. We further conclude that we can obtain improved survival prediction using the RSF model instead of the Cox model. These results are significant because by incorporating more gene expression data with clinical features and using the RSF model, we could develop decision support systems that better utilize heterogeneous information to improve outcome prediction and decision making.
date: 2015-02-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24098/1/journal.pone.0117658.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24098/4/licence.txt
identifier:   Neapolitan, RE and Jiang, X  (2015) Study of integrated heterogeneous data reveals prognostic power of gene expression for breast cancer survival.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117658

relation: http://d-scholarship-dev.library.pitt.edu/29406/
title: Viral infections in outpatients with medically attended acute respiratory illness during the 2012-2013 influenza season
creator: Zimmerman, RK
creator: Rinaldo, CR
creator: Nowalk, MP
creator: Balasubramani, GK
creator: Moehling, KK
creator: Bullotta, A
creator: Eng, HF
creator: Raviotta, JM
creator: Sax, TM
creator: Wisniewski, S
description: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013. Methods: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses. Results: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18-49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary. Conclusions: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.
date: 2015-02-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29406/1/art%253A10.1186%252Fs12879-015-0806-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29406/7/licence.txt
identifier:   Zimmerman, RK and Rinaldo, CR and Nowalk, MP and Balasubramani, GK and Moehling, KK and Bullotta, A and Eng, HF and Raviotta, JM and Sax, TM and Wisniewski, S  (2015) Viral infections in outpatients with medically attended acute respiratory illness during the 2012-2013 influenza season.  BMC Infectious Diseases, 15 (1).       
relation: 10.1186/s12879-015-0806-2

relation: http://d-scholarship-dev.library.pitt.edu/24097/
title: Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR
creator: Taylor, DL
creator: Ante, VM
creator: Bina, XR
creator: Howard, MF
creator: Bina, JE
description: Vibrio cholerae encodes six resistance-nodulation-division (RND) efflux systems which function in antimicrobial resistance, virulence factor production, and intestinal colonization. Among the six RND efflux systems, VexAB exhibited broad substrate specificity and played a predominant role in intrinsic antimicrobial resistance. The VexAB system was encoded in an apparent three gene operon that included vexR; which encodes an uncharacterized TetR family regulator. In this work we examined the role of vexR in vexRAB expression. We found that VexR bound to the vexRAB promoter and vexR deletion resulted in decreased vexRAB expression and increased susceptibility to VexAB antimicrobial substrates. Sub-strate-dependent induction of vexRAB was dependent on vexR and episomal vexR expression provided a growth advantage in the presence of the VexAB substrate deoxycholate. The expression of vexRAB increased, in a vexR-dependent manner, in response to the loss of RND efflux activity. This suggested that VexAB may function to export intracellular metabolites. Support for this hypothesis was provided by data showing that vexRAB was upregulated in several metabolic mutants including tryptophan biosynthetic mutants that were predicted to accumulate indole. In addition, vexRAB was found to be upregulated in response to exogenous indole and to contribute to indole resistance. The collective results indicate that vexR is required for vexRAB expression in response to VexAB substrates and that the VexAB RND efflux system modulates the intracellular levels of metabolites that could otherwise accumulate to toxic levels.
date: 2015-02-19
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24097/1/journal.pone.0117890.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24097/4/licence.txt
identifier:   Taylor, DL and Ante, VM and Bina, XR and Howard, MF and Bina, JE  (2015) Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117890

relation: http://d-scholarship-dev.library.pitt.edu/29408/
title: Adjuvant chemotherapy for stage III colon cancer: Relative dose intensity and survival among veterans
creator: Aspinall, SL
creator: Good, CB
creator: Zhao, X
creator: Cunningham, FE
creator: Heron, BB
creator: Geraci, M
creator: Passero, V
creator: Stone, RA
creator: Smith, KJ
creator: Rogers, R
creator: Shields, J
creator: Sartore, M
creator: Boyle, DP
creator: Giberti, S
creator: Szymanski, J
creator: Smith, D
creator: Ha, A
creator: Sessions, J
creator: Depcinski, S
creator: Fishco, S
creator: Molina, I
creator: Lepir, T
creator: Jean, C
creator: Cruz-Diaz, L
creator: Motta, J
creator: Calderon-Vargas, R
creator: Maland, J
creator: Keefe, S
creator: Tague, M
creator: Leone, A
creator: Glovack, B
creator: Kaplan, B
creator: Cosgriff, S
creator: Kaster, L
creator: Tonnu-Mihara, I
creator: Nguyen, K
creator: Carmichael, J
creator: Clifford, L
creator: Lu, K
creator: Chatta, G
description: Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p<0.001) and 3-year DFS (P=0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin+5-FU/LV (versus 5-FU/LV) (HR=0.55; 95% CI=0.34-0.91), >70% RDI at the first year (HR=0.58; 95% CI=0.37-0.89) and married status (HR=0.66; 95% CI=0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR=2.06; 95% CI=1.25-3.40), Charlson Comorbidity Index (HR=1.17; 95% CI=1.06-1.30), T4 tumor status (versus T1/T2) (HR=5.88; 95% CI=2.69-12.9), N2 node status (HR=1.68; 95% CI=1.12-2.50) and bowel obstruction (HR=2.32, 95% CI=1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.
date: 2015-02-18
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29408/1/art%253A10.1186%252Fs12885-015-1038-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29408/7/licence.txt
identifier:   Aspinall, SL and Good, CB and Zhao, X and Cunningham, FE and Heron, BB and Geraci, M and Passero, V and Stone, RA and Smith, KJ and Rogers, R and Shields, J and Sartore, M and Boyle, DP and Giberti, S and Szymanski, J and Smith, D and Ha, A and Sessions, J and Depcinski, S and Fishco, S and Molina, I and Lepir, T and Jean, C and Cruz-Diaz, L and Motta, J and Calderon-Vargas, R and Maland, J and Keefe, S and Tague, M and Leone, A and Glovack, B and Kaplan, B and Cosgriff, S and Kaster, L and Tonnu-Mihara, I and Nguyen, K and Carmichael, J and Clifford, L and Lu, K and Chatta, G  (2015) Adjuvant chemotherapy for stage III colon cancer: Relative dose intensity and survival among veterans.  BMC Cancer, 15 (1).       
relation: 10.1186/s12885-015-1038-y

relation: http://d-scholarship-dev.library.pitt.edu/24096/
title: Beryllium increases the CD14<sup>dim</sup>CD16+ subset in the lung of chronic beryllium disease
creator: Li, L
creator: Hamzeh, N
creator: Gillespie, M
creator: Elliott, J
creator: Wang, J
creator: Gottschall, EB
creator: Mroz, PM
creator: Maier, LA
description: CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function.
date: 2015-02-17
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24096/1/journal.pone.0117276.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24096/4/licence.txt
identifier:   Li, L and Hamzeh, N and Gillespie, M and Elliott, J and Wang, J and Gottschall, EB and Mroz, PM and Maier, LA  (2015) Beryllium increases the CD14<sup>dim</sup>CD16+ subset in the lung of chronic beryllium disease.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117276

relation: http://d-scholarship-dev.library.pitt.edu/29410/
title: Urinary cortisol and depression in early pregnancy: Role of adiposity and race
creator: Luiza, JW
creator: Gallaher, MJ
creator: Powers, RW
description: Background: Depression before and during pregnancy is associated with adverse birth outcomes including low birth weight and preterm birth. Abnormal maternal cortisol has been hypothesized as one mediator between depression and adverse birth outcomes. The relationship between cortisol and depression in pregnancy is exhibited most strongly in the African American population, and most studies have focused either on circulating or placental levels of cortisol. The utility of urinary cortisol in early pregnancy related to depression and adiposity has not been investigated. Methods: Twenty-five pregnant African American women identified by the Edinburgh Depression Scale as having depression were investigated and matched by body mass index (BMI), age, race, and infant birth weight centile to non-depressed subjects. Maternal urine and plasma cortisol in early pregnancy were quantified and investigated in relation to depression and adiposity. Results: Morning urine cortisol levels tracked positively with plasma cortisol (r2=0.25, p<0.001). However, no differences were observed in either urinary or plasma cortisol between depressed and non-depressed pregnant women. Plasma cortisol was significantly negatively associated with several measures of maternal adiposity including percent body fat (r2=-0.10, p <0.05), however this relationship was present only in the non-depressed women. In a post-hoc analysis, non-depressed non-obese women were found to have significantly higher cortisol levels compared to women with depression, obesity or both (p < 0.05). Conclusions: Depressed pregnant women and non-depressed obese pregnant women evidence atypical cortisol levels compared to non-depressed non-obese pregnant women. Plasma cortisol in early pregnancy is negatively associated with measures of maternal adiposity. Atypical low circulating maternal cortisol among depressed (lean and obese) and non-depressed obese pregnant African American women may indicate hypothalamic-pituitary axis dysfunction in early pregnancy.
date: 2015-02-13
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29410/1/art%253A10.1186%252Fs12884-015-0466-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29410/7/licence.txt
identifier:   Luiza, JW and Gallaher, MJ and Powers, RW  (2015) Urinary cortisol and depression in early pregnancy: Role of adiposity and race.  BMC Pregnancy and Childbirth, 15 (1).       
relation: 10.1186/s12884-015-0466-7

relation: http://d-scholarship-dev.library.pitt.edu/24094/
title: Chronic traumatic encephalopathy in contact sports: A systematic review of all reported pathological cases
creator: Maroon, JC
creator: Winkelman, R
creator: Bost, J
creator: Amos, A
creator: Mathyssek, C
creator: Miele, V
description: © 2015 Maroon et al. Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with head trauma. Although initially believed to affect only boxers, the at-risk population has expanded to encompass a much wider demographic, including American football players, hockey players, wrestlers, and military veterans. This expansion has garnered considerable media attention and public concern for the potential neurodegenerative effects of head trauma. The main aim of this systematic review is to give a complete overview of the common findings and risk factors for CTE as well as the status quo regarding the incidence and prevalence of CTE. This systematic review was performed using PubMed and MEDLINE and includes all neuropathologically confirmed cases of CTE in the medical literature to date, from the first published case in 1954 to August 1, 2013 (n = 153). The demographics, including the primary source of mTBI (mild Traumatic Brain Injury), age and cause of death, ApoE genotype, and history of substance abuse, when listed, were obtained from each case report. The demographics of American football players found to have CTE are also presented separately in order to highlight the most prevalent group of CTE cases reported in recent years. These 153 case reports of CTE represent the largest collection to date. We found that a history of mTBI was the only risk factor consistently associated with CTE. In addition, we found no relationships between CTE and age of death or abnormal ApoE allele. Suicide and the presence of premorbid dementia was not strongly associated with CTE. We conclude that the incidence of CTE remains unknown due to the lack of large, longitudinal studies. Furthermore, the neuropathological and clinical findings related to CTE overlap with many common neurodegenerative diseases. Our review reveals significant limitations of the current CTE case reporting and questions the widespread existence of CTE in contact sports.
date: 2015-02-11
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24094/1/journal.pone.0117338.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24094/4/licence.txt
identifier:   Maroon, JC and Winkelman, R and Bost, J and Amos, A and Mathyssek, C and Miele, V  (2015) Chronic traumatic encephalopathy in contact sports: A systematic review of all reported pathological cases.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117338

relation: http://d-scholarship-dev.library.pitt.edu/24092/
title: Investigation of inter-slice magnetization transfer effects as a new method for MTR imaging of the human brain
creator: Barker, JW
creator: Han, PK
creator: Choi, SH
creator: Bae, KT
creator: Park, SH
description: We present a new method for magnetization transfer (MT) ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP) imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay) and reference images (5-8 s delay) for MT ratio (MTR) imaging of the brain. The effects of varying flip angle and phase encoding (PE) order were investigated experimentally in normal, healthy subjects. Values of up to ∼ 50% and ∼ 40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma.
date: 2015-02-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24092/1/journal.pone.0117101.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24092/4/licence.txt
identifier:   Barker, JW and Han, PK and Choi, SH and Bae, KT and Park, SH  (2015) Investigation of inter-slice magnetization transfer effects as a new method for MTR imaging of the human brain.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117101

relation: http://d-scholarship-dev.library.pitt.edu/24093/
title: Tuberculosis and Hepatic Steatosis Are Prevalent Liver Pathology Findings among HIV-Infected Patients in South Africa
creator: Hoffmann, Christopher J
creator: Hoffmann, Jennifer D
creator: Kensler, Caroline
creator: van der Watt, Martin
creator: Omar, Tanvier
creator: Chaisson, Richard E
creator: Martinson, Neil A
creator: Variava, Ebrahim
publisher: Public Library of Science (PLoS)
date: 2015-02-10
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24093/1/journal.pone.0117813.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24093/4/licence.txt
identifier:   Hoffmann, Christopher J and Hoffmann, Jennifer D and Kensler, Caroline and van der Watt, Martin and Omar, Tanvier and Chaisson, Richard E and Martinson, Neil A and Variava, Ebrahim  (2015) Tuberculosis and Hepatic Steatosis Are Prevalent Liver Pathology Findings among HIV-Infected Patients in South Africa.  PLOS ONE, 10 (2).  e0117813 - e0117813.      
relation: 10.1371/journal.pone.0117813
language: en

relation: http://d-scholarship-dev.library.pitt.edu/24086/
title: Challenges in EGFRvIII detection in head and neck squamous cell carcinoma
creator: Wheeler, SE
creator: Egloff, AM
creator: Wang, L
creator: James, CD
creator: Hammerman, PS
creator: Grandis, JR
description: Objective Head and neck squamous cell carcinoma (HNSCC) accounts for more than 5% of all cancers worldwide. The mortality rate of HNSCC has remained unchanged (approximately 50%) over the last few decades. Ubiquitous overexpression of wild type EGFR in many solid tumors has led to the development of EGFR targeted therapies. EGFR can be constitutively activated via several mechanisms including the truncated, EGFR variant III isoform (EGFRvIII). EGFRvIII lacks exons 2-7 and has been reported to be present in up to 20-40% of HNSCC. EGFRvIII has been shown to contribute to cetuximab resistance. The mechanisms leading to EGFRvIII expression in HNSCC are unknown. The present investigation was undertaken to determine the etiology of EGFRvIII in HNSCC. Materials and Methods Fixed HNSCC and glioma tissues were analyzed by fluorescence in situ hybridization for EGFR amplification. DNA and RNA from fresh frozen specimens were used to determine the presence of EGFRvIII transcripts and the mechanisms of expression via PCR, RT-PCR and RNA sequencing. Results Unlike glioma, EGFRvIII expression in HNSCC did not correlate with EGFR amplification. We found evidence of genomic deletion of the exon 2-7 in 6 of 7 HNSCC cases examined, however, the presence of genomic deletion did not always result in mRNA expression of EGFRvIII. RNA sequencing with automated alignment did not identify EGFRvIII due to microhomology between intron 1 and exon 8. RNA sequencing analyzed by manual alignment methods did not correlate well with RT-PCR and PCR findings. Conclusion These findings suggest that genomic deletion as well as additional regulatory mechanisms may contribute to EGFRvIII expression in HNSCC. Further, large scale automated alignment of sequencing are unlikely to identify EGFRvIII and an assay specifically designed to detect EGFRvIII may be necessary to detect this altered form of EGFR in HNSCC tumors.
date: 2015-02-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24086/1/journal.pone.0117781.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24086/4/licence.txt
identifier:   Wheeler, SE and Egloff, AM and Wang, L and James, CD and Hammerman, PS and Grandis, JR  (2015) Challenges in EGFRvIII detection in head and neck squamous cell carcinoma.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117781

relation: http://d-scholarship-dev.library.pitt.edu/24090/
title: Experience of primary care among homeless individuals with mental health conditions
creator: Chrystal, JG
creator: Glover, DL
creator: Young, AS
creator: Whelan, F
creator: Austin, EL
creator: Johnson, NK
creator: Pollio, DE
creator: Holt, CL
creator: Stringfellow, E
creator: Gordon, AJ
creator: Kim, TA
creator: Daigle, SG
creator: Steward, JL
creator: Kertesz, SG
description: The delivery of primary care to homeless individuals with mental health conditions presents unique challenges. To inform healthcare improvement, we studied predictors of favorable primary care experience among homeless persons with mental health conditions treated at sites that varied in degree of homeless-specific service tailoring. This was a multi-site, survey-based comparison of primary care experiences at three mainstream primary care clinics of the Veterans Administration (VA), one homeless-tailored VA clinic, and one tailored non-VA healthcare program. Persons who accessed primary care service two or more times from July 2008 through June 2010 (N = 366) were randomly sampled. Predictor variables included patient and organization characteristics suggested by the patient perception model developed by Sofaer and Firminger (2005), with an emphasis on mental health. The primary care experience was assessed with the Primary Care Quality-Homeless (PCQ-H) questionnaire, a validated survey instrument. Multiple regression identified predictors of positive experiences (i.e. higher PCQ-H total score). Significant predictors of a positive experience included a site offering tailored service design, perceived choice among providers, and currently domiciled status. There was an interaction effect between site and severe psychiatric symptoms. For persons with severe psychiatric symptoms, a homeless-tailored service design was significantly associated with a more favorable primary care experience. For persons without severe psychiatric symptoms, this difference was not significant. This study supports the importance of tailored healthcare delivery designed for homeless persons' needs, with such services potentially holding special relevance for persons with mental health conditions. To improve patient experience among the homeless, organizations may want to deliver services that are tailored to homelessness and offer a choice of providers.
date: 2015-02-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24090/1/journal.pone.0117395.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24090/4/licence.txt
identifier:   Chrystal, JG and Glover, DL and Young, AS and Whelan, F and Austin, EL and Johnson, NK and Pollio, DE and Holt, CL and Stringfellow, E and Gordon, AJ and Kim, TA and Daigle, SG and Steward, JL and Kertesz, SG  (2015) Experience of primary care among homeless individuals with mental health conditions.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117395

relation: http://d-scholarship-dev.library.pitt.edu/24091/
title: Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: Findings from the Shanghai cohort study
creator: Xu, L
creator: Qu, YH
creator: Chu, XD
creator: Wang, R
creator: Nelson, HH
creator: Gao, YT
creator: Yuan, JM
description: Background: N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods: A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results: Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion: The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection.
date: 2015-02-06
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24091/1/journal.pone.0117326.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24091/4/licence.txt
identifier:   Xu, L and Qu, YH and Chu, XD and Wang, R and Nelson, HH and Gao, YT and Yuan, JM  (2015) Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: Findings from the Shanghai cohort study.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0117326

relation: http://d-scholarship-dev.library.pitt.edu/29412/
title: The role of IL-27 in susceptibility to post-influenza Staphylococcus aureus pneumonia
creator: Robinson, KM
creator: Lee, B
creator: Scheller, EV
creator: Mandalapu, S
creator: Enelow, RI
creator: Kolls, JK
creator: Alcorn, JF
description: Background: Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection.Methods: A murine model of influenza and Staphylococcus aureus infection was used to mimic human viral, bacterial co-infection. C57BL/6 wild-type, IL-27 receptor α knock-out, and IL-10 knock-out mice were infected with Influenza H1N1 (A/PR/8/34) or vehicle for 6 days followed by challenge with Staphylococcus aureus or vehicle for 24 hours. Lung inflammation, bacterial burden, gene expression, and cytokine production were determined.Results: IL-27 receptor α knock-out mice challenged with influenza A had increased morbidity compared to controls, but no change in viral burden. IL-27 receptor α knock-out mice infected with influenza displayed significantly decreased IL-10 production compared to wild-type. IL-27 receptor α knock-out mice co-infected with influenza and S. aureus had improved bacterial clearance compared to wild-type controls. Importantly, there were significantly increased Type 17 responses and decreased IL-10 production in IL-27 receptor α knock-out mice. Dual infected IL-10-/- mice had significantly less bacterial burden compared to dual infected WT mice.Conclusions: These data reveal that IL-27 regulates enhanced susceptibility to S. aureus pneumonia following influenza infection, potentially through the induction of IL-10 and suppression of IL-17.
date: 2015-02-05
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29412/1/art%253A10.1186%252Fs12931-015-0168-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29412/7/licence.txt
identifier:   Robinson, KM and Lee, B and Scheller, EV and Mandalapu, S and Enelow, RI and Kolls, JK and Alcorn, JF  (2015) The role of IL-27 in susceptibility to post-influenza Staphylococcus aureus pneumonia.  Respiratory Research, 16 (1).   ISSN 1465-9921     
relation: 10.1186/s12931-015-0168-8

relation: http://d-scholarship-dev.library.pitt.edu/29416/
title: Interactive pre-surgical design of optimal extra-cardiac Fontan connections starting with cardiac MRI reconstructions of the Glenn anastomosis
creator: Menon, PG
creator: Hong, H
date: 2015-02-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29416/1/art%253A10.1186%252F1532-429X-17-S1-P197.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29416/7/licence.txt
identifier:   Menon, PG and Hong, H  (2015) Interactive pre-surgical design of optimal extra-cardiac Fontan connections starting with cardiac MRI reconstructions of the Glenn anastomosis.  Journal of Cardiovascular Magnetic Resonance.  1 - 2.  ISSN 1097-6647     
relation: 10.1186/1532-429X-17-S1-P197

relation: http://d-scholarship-dev.library.pitt.edu/24085/
title: Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: Cross-sectional findings from the lifestyle interventions and independence for elders (LIFE) study
creator: Bann, D
creator: Hire, D
creator: Manini, T
creator: Cooper, R
creator: Botoseneanu, A
creator: McDermott, MM
creator: Pahor, M
creator: Glynn, NW
creator: Fielding, R
creator: King, AC
creator: Church, T
creator: Ambrosius, WT
creator: Gill, T
description: Background: Identifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time-assessed both objectively and by self-report-with body mass index (BMI) and grip strength in a large sample of older adults. Methods: We used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3-7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression. Results: Greater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength. Conclusions: In this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences.
date: 2015-02-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24085/1/journal.pone.0116058.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24085/4/licence.txt
identifier:   Bann, D and Hire, D and Manini, T and Cooper, R and Botoseneanu, A and McDermott, MM and Pahor, M and Glynn, NW and Fielding, R and King, AC and Church, T and Ambrosius, WT and Gill, T  (2015) Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: Cross-sectional findings from the lifestyle interventions and independence for elders (LIFE) study.  PLoS ONE, 10 (2).       
relation: 10.1371/journal.pone.0116058

relation: http://d-scholarship-dev.library.pitt.edu/29413/
title: Myocardial fibrosis is associated with subsequent death and hospitalization for heart failure in obese adults
creator: Fridman, Y
creator: Wong, TC
creator: Piehler, KM
creator: Zareba, KM
creator: Moon, J
creator: Ugander, M
creator: Messroghli, D
creator: Jakicic, JM
creator: Valeti, U
creator: Chang, CC
creator: Shroff, SG
creator: Miller, CA
creator: Schmitt, M
creator: Kellman, P
creator: Butler, J
creator: Gheorghiade, M
creator: Schelbert, EB
date: 2015-02-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29413/1/art%253A10.1186%252F1532-429X-17-S1-M8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29413/7/licence.txt
identifier:   Fridman, Y and Wong, TC and Piehler, KM and Zareba, KM and Moon, J and Ugander, M and Messroghli, D and Jakicic, JM and Valeti, U and Chang, CC and Shroff, SG and Miller, CA and Schmitt, M and Kellman, P and Butler, J and Gheorghiade, M and Schelbert, EB  (2015) Myocardial fibrosis is associated with subsequent death and hospitalization for heart failure in obese adults.  Journal of Cardiovascular Magnetic Resonance.  1 - 2.  ISSN 1097-6647     
relation: 10.1186/1532-429X-17-S1-M8

relation: http://d-scholarship-dev.library.pitt.edu/29417/
title: The association of global longitudinal and global circumferential strain with ejection fraction in patients with aortic stenosis and increased left ventricular mass: A feature tracking CMR study
creator: Cavalcante, JL
creator: Delgado-Montero, A
creator: Rijal, S
creator: Schelbert, EB
creator: Gorcsan, J
date: 2015-02-03
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29417/1/art%253A10.1186%252F1532-429X-17-S1-P226.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29417/7/licence.txt
identifier:   Cavalcante, JL and Delgado-Montero, A and Rijal, S and Schelbert, EB and Gorcsan, J  (2015) The association of global longitudinal and global circumferential strain with ejection fraction in patients with aortic stenosis and increased left ventricular mass: A feature tracking CMR study.  Journal of Cardiovascular Magnetic Resonance.  1 - 2.  ISSN 1097-6647     
relation: 10.1186/1532-429X-17-S1-P226

relation: http://d-scholarship-dev.library.pitt.edu/24083/
title: Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells
creator: Furukawa, M
creator: Wheeler, S
creator: Clark, AM
creator: Wells, A
description: Purpose: The lung is one of the most common sites of breast cancer metastasis. While metastatic seeding is often accompanied by a dormancy-promoting mesenchymal to epithelial reverting transitions (MErT), we aimed to determine whether lung epithelial cells can impart this phenotype on aggressive breast cancer cells. Methods: Co-culture experiments of normal lung epithelial cell lines (SAEC, NHBE or BEAS-2B) and breast cancer cell lines (MCF-7 or MDA-MB-231) were conducted. Flow cytometry analysis, immunofluorescence staining for E-cadherin or Ki-67 and senescence associated beta-galactosidase assays assessed breast cancer cell outgrowth and phenotype. Results: Co-culture of the breast cancer cells with the normal lung cells had different effects on the epithelial and mesenchymal carcinoma cells. The epithelial MCF-7 cells were increased in number but still clustered even if in a slightly more mesenchymal-spindle morphology. On the other hand, the mesenchymal MDA-MB-231 cells survived but did not progressively grow out in co-culture. These aggressive carcinoma cells underwent an epithelial shift as indicated by cuboidal morphology and increased E-cadherin. Disruption of E-cadherin expressed in MDA-MB-231 using shRNA prevented this phenotypic reversion in co-culture. Lung cells limited cancer cell growth kinetics as noted by both (1) some of the cells becoming larger and positive for senescencemarkers/negative for proliferation marker Ki-67, and (2) Ki-67 positive cells significantly decreasing in MDA-MB-231 and MCF-7 cells after co-culture. Conclusions: Our data indicate that normal lung epithelial cells can drive an epithelial phenotype and suppress the growth kinetics of breast cancer cells coincident with changing their phenotypes.
date: 2015-01-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24083/1/journal.pone.0118060.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24083/4/licence.txt
identifier:   Furukawa, M and Wheeler, S and Clark, AM and Wells, A  (2015) Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells.  PLoS ONE, 10 (1).       
relation: 10.1371/journal.pone.0118060

relation: http://d-scholarship-dev.library.pitt.edu/24084/
title: Repression of CC16 by cigarette smoke (CS) exposure
creator: Zhu, L
creator: Di, PYP
creator: Wu, R
creator: Pinkerton, KE
creator: Chen, Y
description: Club (Clara) Cell Secretory Protein (CCSP, or CC16) is produced mainly by non-ciliated airway epithelial cells including bronchiolar club cells and the change of its expression has been shown to associate with the progress and severity of Chronic Obstructive Pulmonary Disease (COPD). In an animal model, the lack of CC16 renders the animal susceptible to the tumorigenic effect of a major CS carcinogen. A recent population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD) has indicated that the low serum CC16 concentration is closely linked with the smoke-related mortality, particularly that driven by the lung cancer. However, the study of CC16 expression in well-defined smoke exposure models has been lacking, and there is no experimental support for the potential causal link between CC16 and CS-induced pathophysiological changes in the lung. In the present study, we have found that airway CC16 expression was significantly repressed in COPD patients, in monkey CS exposure model, and in CS-induced mouse model of COPD. Additionally, the lack of CC16 exacerbated airway inflammation and alveolar loss in the mouse model. Therefore, CC16 may play an important protective role in CS-related diseases.
date: 2015-01-30
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24084/1/journal.pone.0116159.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24084/4/licence.txt
identifier:   Zhu, L and Di, PYP and Wu, R and Pinkerton, KE and Chen, Y  (2015) Repression of CC16 by cigarette smoke (CS) exposure.  PLoS ONE, 10 (1).       
relation: 10.1371/journal.pone.0116159

relation: http://d-scholarship-dev.library.pitt.edu/29419/
title: Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: A nationwide retrospective cohort study
creator: Alvarez, CA
creator: Mortensen, EM
creator: Makris, UE
creator: Berlowitz, DR
creator: Copeland, LA
creator: Good, CB
creator: Amuan, ME
creator: Pugh, MJV
description: Background: High-risk medication exposure in the elderly is common and associated with increased mortality, hospitalizations, and emergency department (ED) visits. Skeletal muscle relaxants and antihistamines are high-risk medications commonly prescribed in elderly patients. The objective of this study was to determine the association between skeletal muscle relaxants or antihistamines and mortality, hospitalizations, and emergency department visits. Methods: This study used a new-user, retrospective cohort design using national Veteran Affairs (VA) data from 128 hospitals. Veterans ≥65 years of age on October 1, 2005 who received VA inpatient/outpatient care at least once in each of fiscal year (FY) 2005 and FY 2006 were included. Exposure to skeletal muscle relaxants and antihistamines was defined by the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set measures for high-risk medications in the elderly. Primary outcomes identified within one year of exposure were death, ED visit, or hospitalization; ED visits or hospitalizations due to falls and fracture were also assessed. Propensity score matching (1 to 1 match) was used to balance covariates between exposed patients and non-exposed patients. Results: In this cohort of 1,807,404 patients 55,566 patients were included in the propensity-matched cohort for skeletal muscle relaxants and 60,058 patients were included in the propensity-matched cohort for anti-histamines. Mortality was lower in skeletal muscle relaxants-exposed patients (adjusted odds ratio [AOR] 0.87, 95% CI 0.81-0.94), but risk of emergency care (AOR 2.25, 95% CI 2.16-2.33) and hospitalization (AOR 1.56, 95% CI 1.48-1.65) was higher for patients prescribed skeletal muscle relaxants. Similar findings were observed for emergency and hospital care for falls or fractures. Mortality (AOR 1.93, 95% CI 1.82-2.04), ED visits (AOR 2.35, 95% CI 2.27-2.43), and hospitalizations (AOR 2.21, 95% CI 2.11-2.32) were higher in the antihistamine-exposed group, with similar findings for falls and fractures outcomes. Conclusion: Skeletal muscle relaxants and antihistamines are associated with an increased risk of ED visits and hospitalizations in elderly patients. Antihistamines were also associated with an increased risk of death, further validating the classification of these drug classes as "high risk".
date: 2015-01-27
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29419/1/art%253A10.1186%252F1471-2318-15-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29419/7/licence.txt
identifier:   Alvarez, CA and Mortensen, EM and Makris, UE and Berlowitz, DR and Copeland, LA and Good, CB and Amuan, ME and Pugh, MJV  (2015) Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: A nationwide retrospective cohort study.  BMC Geriatrics, 15 (1).       
relation: 10.1186/1471-2318-15-2

relation: http://d-scholarship-dev.library.pitt.edu/29420/
title: Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities
creator: Mitra, M
creator: Singer, D
creator: Mano, Y
creator: Hritz, J
creator: Nam, G
creator: Gorelick, RJ
creator: Byeon, IJL
creator: Gronenborn, AM
creator: Iwatani, Y
creator: Levin, JG
description: Background: Human APOBEC3H (A3H) belongs to the A3 family of host restriction factors, which are cytidine deaminases that catalyze conversion of deoxycytidine to deoxyuridine in single-stranded DNA. A3 proteins contain either one (A3A, A3C, A3H) or two (A3B, A3D, A3F, A3G) Zn-binding domains. A3H has seven haplotypes (I-VII) that exhibit diverse biological phenotypes and geographical distribution in the human population. Its single Zn-coordinating deaminase domain belongs to a phylogenetic cluster (Z3) that is different from the Z1- and Z2-type domains in other human A3 proteins. A3H HapII, unlike A3A or A3C, has potent activity against HIV-1. Here, we sought to identify the determinants of A3H HapII deaminase and antiviral activities, using site-directed sequence- and structure-guided mutagenesis together with cell-based, biochemical, and HIV-1 infectivity assays. Results: We have constructed a homology model of A3H HapII, which is similar to the known structures of other A3 proteins. The model revealed a large cluster of basic residues (not present in A3A or A3C) that are likely to be involved in nucleic acid binding. Indeed, RNase A pretreatment of 293T cell lysates expressing A3H was shown to be required for detection of deaminase activity, indicating that interaction with cellular RNAs inhibits A3H catalytic function. Similar observations have been made with A3G. Analysis of A3H deaminase substrate specificity demonstrated that a 5" T adjacent to the catalytic C is preferred. Changing the putative nucleic acid binding residues identified by the model resulted in reduction or abrogation of enzymatic activity, while substituting Z3-specific residues in A3H to the corresponding residues in other A3 proteins did not affect enzyme function. As shown for A3G and A3F, some A3H mutants were defective in catalysis, but retained antiviral activity against HIV-1vif (-) virions. Furthermore, endogenous reverse transcription assays demonstrated that the E56A catalytic mutant inhibits HIV-1 DNA synthesis, although not as efficiently as wild type. Conclusions: The molecular and biological activities of A3H are more similar to those of the double-domain A3 proteins than to those of A3A or A3C. Importantly, A3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication.
date: 2015-01-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29420/1/art%253A10.1186%252Fs12977-014-0130-8.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29420/7/licence.txt
identifier:   Mitra, M and Singer, D and Mano, Y and Hritz, J and Nam, G and Gorelick, RJ and Byeon, IJL and Gronenborn, AM and Iwatani, Y and Levin, JG  (2015) Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities.  Retrovirology, 12 (1).       
relation: 10.1186/s12977-014-0130-8

relation: http://d-scholarship-dev.library.pitt.edu/29421/
title: Computer-supported feedback message tailoring: Theory-informed adaptation of clinical audit and feedback for learning and behavior change
creator: Landis-Lewis, Z
creator: Brehaut, JC
creator: Hochheiser, H
creator: Douglas, GP
creator: Jacobson, RS
description: Background: Evidence shows that clinical audit and feedback can significantly improve compliance with desired practice, but it is unclear when and how it is effective. Audit and feedback is likely to be more effective when feedback messages can influence barriers to behavior change, but barriers to change differ across individual health-care providers, stemming from differences in providers' individual characteristics. Discussion: The purpose of this article is to invite debate and direct research attention towards a novel audit and feedback component that could enable interventions to adapt to barriers to behavior change for individual health-care providers: computer-supported tailoring of feedback messages. We argue that, by leveraging available clinical data, theory-informed knowledge about behavior change, and the knowledge of clinical supervisors or peers who deliver feedback messages, a software application that supports feedback message tailoring could improve feedback message relevance for barriers to behavior change, thereby increasing the effectiveness of audit and feedback interventions. We describe a prototype system that supports the provision of tailored feedback messages by generating a menu of graphical and textual messages with associated descriptions of targeted barriers to behavior change. Supervisors could use the menu to select messages based on their awareness of each feedback recipient's specific barriers to behavior change. We anticipate that such a system, if designed appropriately, could guide supervisors towards giving more effective feedback for health-care providers. Summary: A foundation of evidence and knowledge in related health research domains supports the development of feedback message tailoring systems for clinical audit and feedback. Creating and evaluating computer-supported feedback tailoring tools is a promising approach to improving the effectiveness of clinical audit and feedback.
date: 2015-01-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29421/1/art%253A10.1186%252Fs13012-014-0203-z.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29421/7/licence.txt
identifier:   Landis-Lewis, Z and Brehaut, JC and Hochheiser, H and Douglas, GP and Jacobson, RS  (2015) Computer-supported feedback message tailoring: Theory-informed adaptation of clinical audit and feedback for learning and behavior change.  Implementation Science, 10 (1).       
relation: 10.1186/s13012-014-0203-z

relation: http://d-scholarship-dev.library.pitt.edu/29423/
title: Discovering monotonic stemness marker genes from time-series stem cell microarray data
creator: Wang, HW
creator: Sun, HJ
creator: Chang, TY
creator: Lo, HH
creator: Cheng, WC
creator: Tseng, GC
creator: Lin, CT
creator: Chang, SJ
creator: Pal, NR
creator: Chung, IF
description: Background: Identification of genes with ascending or descending monotonic expression patterns over time or stages of stem cells is an important issue in time-series microarray data analysis. We propose a method named Monotonic Feature Selector (MFSelector) based on a concept of total discriminating error (DEtotal) to identify monotonic genes. MFSelector considers various time stages in stage order (i.e., Stage One vs. other stages, Stages One and Two vs. remaining stages and so on) and computes DEtotal of each gene. MFSelector can successfully identify genes with monotonic characteristics.Results: We have demonstrated the effectiveness of MFSelector on two synthetic data sets and two stem cell differentiation data sets: embryonic stem cell neurogenesis (ESCN) and embryonic stem cell vasculogenesis (ESCV) data sets. We have also performed extensive quantitative comparisons of the three monotonic gene selection approaches. Some of the monotonic marker genes such as OCT4, NANOG, BLBP, discovered from the ESCN dataset exhibit consistent behavior with that reported in other studies. The role of monotonic genes found by MFSelector in either stemness or differentiation is validated using information obtained from Gene Ontology analysis and other literature. We justify and demonstrate that descending genes are involved in the proliferation or self-renewal activity of stem cells, while ascending genes are involved in differentiation of stem cells into variant cell lineages.Conclusions: We have developed a novel system, easy to use even with no pre-existing knowledge, to identify gene sets with monotonic expression patterns in multi-stage as well as in time-series genomics matrices. The case studies on ESCN and ESCV have helped to get a better understanding of stemness and differentiation. The novel monotonic marker genes discovered from a data set are found to exhibit consistent behavior in another independent data set, demonstrating the utility of the proposed method. The MFSelector R function and data sets can be downloaded from: http://microarray.ym.edu.tw/tools/MFSelector/.
date: 2015-01-21
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29423/1/art%253A10.1186%252F1471-2164-16-S2-S2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29423/7/licence.txt
identifier:   Wang, HW and Sun, HJ and Chang, TY and Lo, HH and Cheng, WC and Tseng, GC and Lin, CT and Chang, SJ and Pal, NR and Chung, IF  (2015) Discovering monotonic stemness marker genes from time-series stem cell microarray data.  BMC Genomics, 16.       
relation: 10.1186/1471-2164-16-S2-S2

relation: http://d-scholarship-dev.library.pitt.edu/26695/
title: Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P
creator: Chen, FH
creator: Dong, GH
creator: Zhang, DJ
creator: Liu, XY
creator: Jia, X
creator: An, CB
creator: Ma, MM
creator: Xie, YW
creator: Barton, L
creator: Ren, XY
creator: Zhao, ZJ
creator: Wu, XHW
creator: Jones, MK
description: Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.
date: 2015-01-16
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26695/1/licence.txt
identifier:   Chen, FH and Dong, GH and Zhang, DJ and Liu, XY and Jia, X and An, CB and Ma, MM and Xie, YW and Barton, L and Ren, XY and Zhao, ZJ and Wu, XHW and Jones, MK  (2015) Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.  Science, 347 (6219).  248 - 250.  ISSN 0036-8075     
relation: 10.1126/science.1259172

relation: http://d-scholarship-dev.library.pitt.edu/29424/
title: Reintubation in critically ill patients: Procedural complications and implications for care
creator: Elmer, J
creator: Lee, S
creator: Rittenberger, JC
creator: Dargin, J
creator: Winger, D
creator: Emlet, L
description: Introduction: In critically ill patients, re-intubation is common and may be a high-risk procedure. Anticipating a difficult airway and identifying high-risk patients can allow time for life-saving preparation. Unfortunately, prospective studies have not compared the difficulty or complication rates associated with reintubation in this population. Methods: We performed a secondary analysis of a prospective registry of in-hospital emergency airway management, focusing on patients that underwent multiple out-of-operating room intubations during a single hospitalization. Our main outcomes of interest were technical difficulty of intubation (number of attempts, need for adjuncts to direct laryngoscopy, best Cormack-Lehane grade and training level of final intubator) and the frequency of procedural complications (aspiration, arrhythmia, airway trauma, new hypotension, new hypoxia, esophageal intubation and cardiac arrest). We compared the cohort of reintubated patients to a matched cohort of singly intubated patients and compared each repeatedly intubated patient's first and last intubation. Results: Our registry included 1053 patients, of which 151 patients (14%) were repeatedly intubated (median two per patient). Complications were significantly more common during last intubation compared to first (13% versus 5%, P = 0.02). The most common complications were hypotension (41%) and hypoxia (35%). These occurred despite no difference in any measure of technical difficultly across intubations. Conclusion: In this cohort of reintubated patients, clinically important procedural complications were significantly more common on last intubation compared to first.
date: 2015-01-16
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29424/1/art%253A10.1186%252Fs13054-014-0730-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29424/7/licence.txt
identifier:   Elmer, J and Lee, S and Rittenberger, JC and Dargin, J and Winger, D and Emlet, L  (2015) Reintubation in critically ill patients: Procedural complications and implications for care.  Critical Care, 19 (1).   ISSN 1364-8535     
relation: 10.1186/s13054-014-0730-7

relation: http://d-scholarship-dev.library.pitt.edu/29426/
title: Targeting multiple inhibitory receptors to reverse melanoma-induced T cell dysfunction
creator: Zarour, HM
date: 2015-01-15
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29426/1/art%253A10.1186%252F1479-5876-13-S1-K14.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29426/7/licence.txt
identifier:   Zarour, HM  (2015) Targeting multiple inhibitory receptors to reverse melanoma-induced T cell dysfunction.  Journal of Translational Medicine.  1 - 1.      
relation: 10.1186/1479-5876-13-S1-K14

relation: http://d-scholarship-dev.library.pitt.edu/25653/
title: Rearrangement reactions of 1,1-divinyl-2-phenylcyclopropanes
creator: Hay, EB
creator: Zhang, H
creator: Curran, DP
description: 1,1-Divinyl-2-phenylcyclopropanes are entry points to a rich area of rearrangement chemistry. With N,N-diallyl amide substrates, tandem radical cyclizations can be initiated at room temperature. Warming provides products of pure thermal rearrangements with acids, ester, and amides. These isomerizations give vinylcyclopentenes resulting from divinylcyclopropane rearrangements and more deeply rearranged tricyclic spirolactams resulting from aromatic Cope rearrangements followed by ene reactions. Conversion of the carbonyl group to an alcohol or ether opens retro-ene pathways followed by either tautomerization or Claisen rearrangement.
date: 2015-01-14
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25653/1/licence.txt
identifier:   Hay, EB and Zhang, H and Curran, DP  (2015) Rearrangement reactions of 1,1-divinyl-2-phenylcyclopropanes.  Journal of the American Chemical Society, 137 (1).  322 - 327.  ISSN 0002-7863     
relation: 10.1021/ja510608u

relation: http://d-scholarship-dev.library.pitt.edu/29427/
title: A comparative analysis of swallowing accelerometry and sounds during saliva swallows
creator: Dudik, JM
creator: Jestrović, I
creator: Luan, B
creator: Coyle, JL
creator: Sejdić, E
description: Background: Accelerometry (the measurement of vibrations) and auscultation (the measurement of sounds) are both non-invasive techniques that have been explored for their potential to detect abnormalities in swallowing. The differences between these techniques and the information they capture about swallowing have not previously been explored in a direct comparison. Methods: In this study, we investigated the differences between dual-axis swallowing accelerometry and swallowing sounds by recording data from adult participants and calculating a number of time and frequency domain features. During the experiment, 55 participants (ages 18-65) were asked to complete five saliva swallows in a neutral head position. The resulting data was processed using previously designed techniques including wavelet denoising, spline filtering, and fuzzy means segmentation. The pre-processed signals were then used to calculate 9 time, frequency, and time-frequency domain features for each independent signal. Wilcoxon signed-rank and Wilcoxon rank-sum tests were utilized to compare feature values across transducers and patient demographics, respectively. Results: In addition to finding a number of features that varied between male and female participants, our statistical analysis determined that the majority of our chosen features were statistically significantly different across the two sensor methods and that the dependence on within-subject factors varied with the transducer type. However, a regression analysis showed that age accounted for an insignificant amount of variation in our signals. Conclusions: We conclude that swallowing accelerometry and swallowing sounds provide different information about deglutition despite utilizing similar transduction methods. This contradicts past assumptions in the field and necessitates the development of separate analysis and processing techniques for swallowing sounds and vibrations.
date: 2015-01-12
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29427/1/art%253A10.1186%252F1475-925X-14-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29427/7/licence.txt
identifier:   Dudik, JM and Jestrović, I and Luan, B and Coyle, JL and Sejdić, E  (2015) A comparative analysis of swallowing accelerometry and sounds during saliva swallows.  BioMedical Engineering Online, 14 (1).       
relation: 10.1186/1475-925X-14-3

relation: http://d-scholarship-dev.library.pitt.edu/28200/
title: Simulating and visualizing sidewalk accessibility for wayfinding of people with disabilities
creator: Tajgardoon, M
creator: Karimi, HA
description: There are generally different and less wayfinding options for pedestrians than those for drivers. This makes developing models and tools that assist pedestrians in finding routes more challenging. The problem is even further exacerbated when specific routing requirements of people with disabilities are considered. While currently much research is focused on developing solutions for wayfinding of pedestrians, very few address the specific requirements of individuals with disabilities and none is focused on evaluation of the accessibility of built environments. In this paper, we propose a new approach in evaluating the accessibility of built environments for wayfinding of individuals with disabilities. The proposed approach involves simulation and visualization of the accessibility of sidewalk segments allowing urban planners, and other designers and engineers, to gain an understanding of how accessible built environments are and allowing individuals with disabilities to assess the accessibility of built environments with respect to their mobility needs. Simulations were conducted using a sidewalk network database which contains accessibility attributes based on the standards recommended by the Americans with Disabilities Act. To demonstrate the benefits of the proposed approach, a representative model was used to simulate scenarios for the wayfinding requirements at both community and individual levels. The results of the simulations are visualized in heat-maps.
date: 2015-01-02
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28200/1/Simulating_and_visualizing_sidewalk_accessibility_for_wayfinding_of_people_with_disabilities.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28200/4/licence.txt
identifier:   Tajgardoon, M and Karimi, HA  (2015) Simulating and visualizing sidewalk accessibility for wayfinding of people with disabilities.  International Journal of Cartography, 1 (1).  79 - 93.      
relation: 10.1080/23729333.2015.1055646

relation: http://d-scholarship-dev.library.pitt.edu/28572/
title: ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry
creator: Shu, Q
creator: Lennemann, NJ
creator: Sarkar, SN
creator: Sadovsky, Y
creator: Coyne, CB
description: Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and PI(3,4)P2. We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles. Utilizing two techniques—light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization—we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28572/1/journal.ppat.1005150.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28572/3/licence.txt
identifier:   Shu, Q and Lennemann, NJ and Sarkar, SN and Sadovsky, Y and Coyne, CB  (2015) ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry.  PLoS Pathogens, 11 (9).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1005150

relation: http://d-scholarship-dev.library.pitt.edu/21789/
title: Adaptive sub-carrier level power allocation in OFDMA networks
creator: Singh, S
creator: Shahbazi, M
creator: Pelechrinis, K
creator: Sundaresan, K
creator: Krishnamurthy, SV
creator: Addepalli, S
description: In today's OFDMA networks, the transmission power is typically fixed and the same for all the sub-carriers that compose a channel. The sub-carriers though, experience different degrees of fading and thus, the received power is different for different sub-carriers; while some frequencies experience deep fades, others are relatively unaffected. In this paper, we make a case for redistributing the power across the sub-carriers (subject to a fixed power budget constraint) to better cope with this frequency selectivity. Specifically, we design a joint power and rate adaptation scheme (called JPRA for short) wherein power redistribution is combined with sub-carrier level rate adaptation to yield significant throughput benefits. We further consider three variants of JPRA: (a) JPRA-Basic where, the power is redistributed across sub-carriers so as to support a maximum common rate across all the sub-carriers (b) JPRA-Intermediate where, the power is redistributed across sub-carriers so as to support a maximum common rate across a 'subset' of sub-carriers such that the aggregate rate is maximized. (c) JPRA-Adaptive where, the goal is to redistribute power such that the transmission time of a packet is minimized. While the first two variants decrease transceiver complexity and are simpler, the third is geared towards achieving the maximum throughput possible. We implement all three variants of JPRA on our WARP radio testbed. Our extensive experiments demonstrate that JPRA can provide a 35 percent improvement in total network throughput in testbed experiments compared to FARA, a scheme where only sub-carrier level rate adaptation is used. We also perform simulations to demonstrate the efficacy of JPRA in larger scale networks.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/21789/1/licence.txt
identifier:   Singh, S and Shahbazi, M and Pelechrinis, K and Sundaresan, K and Krishnamurthy, SV and Addepalli, S  (2015) Adaptive sub-carrier level power allocation in OFDMA networks.  IEEE Transactions on Mobile Computing, 14 (1).  28 - 41.  ISSN 1536-1233     
relation: 10.1109/TMC.2014.2312716

relation: http://d-scholarship-dev.library.pitt.edu/29286/
title: Addressing Individual Perspectives in the Development of Schoolwide Rules: A Data-Informed Process
creator: Valenti, MW
creator: Kerr, MM
description: Consensus among the majority of staff is essential for the development and consistent implementation of the Schoolwide Positive Behavior Interventions and Supports (SWPBIS) framework. At the universal level, a shared vision reflects consensus regarding operational definitions of behaviors (rules) and consequences. Yet, decades of research indicate that educators possess idiosyncratic standards for student behaviors. Lengthy and often unproductive discussions can arise when discussing school rules with a large group of adults. To address situations where consensus is difficult to achieve, this article outlines a process that assesses and summarizes the views of all school-based staff and then facilitates discussions based on the aggregated data. To illustrate this approach, we include two case studies involving faculty members struggling to find consensus about their schoolwide rules and describe how agreement was achieved. Recommendations for SWPBIS coaches conclude the article.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/msword
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29286/1/Addressing%20Individual%20Perspectives%20-%20JPBI-13-115%20R2.doc
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29286/3/licence.txt
identifier:   Valenti, MW and Kerr, MM  (2015) Addressing Individual Perspectives in the Development of Schoolwide Rules: A Data-Informed Process.  Journal of Positive Behavior Interventions, 17 (4).  245 - 253.  ISSN 1098-3007     
relation: 10.1177/1098300714544405

relation: http://d-scholarship-dev.library.pitt.edu/29392/
title: Ambient ozone exposure and children's acute asthma in New York City: A case-crossover analysis Children s Environmental Health
creator: Sheffield, PE
creator: Zhou, J
creator: Shmool, JLC
creator: Clougherty, JE
description: Background: Childhood asthma morbidity has been associated with ambient ozone in case-crossover studies. Varying effects of ozone by child age and sex, however, have been less explored. Methods: This study evaluates associations between ozone exposure and asthma emergency department visits and hospitalizations among boys and girls aged 5-17 years in New York City for the 2005-2011 warm season period. Time-stratified case-crossover analysis was conducted and, for comparison, time-series analysis controlling for season, day-of-week, same-day and delayed effects of temperature and relative humidity were also performed. Results: We found associations between ambient ozone levels and childhood asthma emergency department visits and hospitalizations in New York City, although the relationships varied among boys and girls and by age group. For an increase of interquartile range (0.013 ppm) in ozone, there was a 2.9-8.4% increased risk for boys and 5.4-6.5% for girls in asthma emergency department visits; and 8.2% increased risk for girls in hospitalizations. Among girls, we observed stronger associations among older children (10-13 and 14-17 year age groups). We did not observe significant modification by age for boys. Boys exhibited a more prompt response (lag day 1) to ozone than did girls (lag day 3), but significant associations for girls were retained longer, through lag day 6. Conclusions: Our study indicates significant variance in associations between short-term ozone concentrations and asthma events by child sex and age. Differences in ozone response for boys and girls, before and after puberty, may point towards both social (gendered) and biological (sex-linked) sources of effect modification.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29392/1/art%253A10.1186%252Fs12940-015-0010-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29392/7/licence.txt
identifier:   Sheffield, PE and Zhou, J and Shmool, JLC and Clougherty, JE  (2015) Ambient ozone exposure and children's acute asthma in New York City: A case-crossover analysis Children s Environmental Health.  Environmental Health: A Global Access Science Source, 14 (1).       
relation: 10.1186/s12940-015-0010-2

relation: http://d-scholarship-dev.library.pitt.edu/23943/
title: Associations between changes in normal personality traits and borderline personality disorder symptoms over 16 years
creator: Wright, AGC
creator: Hopwood, CJ
creator: Zanarini, MC
description: There has been significant movement toward conceptualizing borderline personality disorder (BPD) with normal personality traits. However, 1 critical assumption underlying this transition, that longitudinal trajectories of BPD symptoms and normal traits track together, has not been tested. We evaluated the prospective longitudinal associations of changes in Five-Factor Model traits and BPD symptoms over the course of 16 years using parallel process latent growth curve models in 362 patients with BPD (n = 290) or other PDs (n = 72). Moderate to strong cross-sectional and longitudinal associations were observed between BPD symptoms and Neuroticism, Extraversion, Agreeableness, and Conscientiousness. This study is the first to demonstrate a longitudinal link between changes in BPD symptoms and changes in traits over an extended interval in a clinical sample. These findings imply that changes in BPD symptoms occur in concert with changes in normal traits, and support the proposed transition to conceptualizing BPD, at least in part, with trait dimensions.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/23943/1/licence.txt
identifier:   Wright, AGC and Hopwood, CJ and Zanarini, MC  (2015) Associations between changes in normal personality traits and borderline personality disorder symptoms over 16 years.  Personality Disorders: Theory, Research, and Treatment, 6 (1).  1 - 11.  ISSN 1949-2715     
relation: 10.1037/per0000092

relation: http://d-scholarship-dev.library.pitt.edu/29266/
title: Asthma and obesity: Mechanisms and clinical implications
description: Obesity is the most common asthma co-morbidity; it has been associated with increased risk for asthma exacerbations, worse respiratory symptoms and poor control. The exact mechanisms remain elusive and are probably multifactorial, stemming from mechanical alterations of the airways and lung parenchyma, to systemic and airway inflammatory and metabolic dysregulation that adversely influences lung function and or response to therapy. However, the fact that not every obese asthmatic is equally affected by weight gain highlights the many challenges and complexities in understanding this association. The factors that determine susceptibility may not depend on being obese alone, but rather the interactions with other phenotypical characteristics, such as age of asthma onset, gender and race to name a few. Inability to account for asthma phenotypes that are differentially affected by increasing body mass index (BMI) may contribute to the lack of consistent results across studies. This review will provide a succinct summary of obesity-related mechanisms and the clinical impact on asthma including highlights on recent progress.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29266/1/art%253A10.1186%252Fs40733-015-0005-3.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29266/7/licence.txt
identifier:   UNSPECIFIED  (2015) Asthma and obesity: Mechanisms and clinical implications.  Asthma Research and Practice, 1 (1).       
relation: 10.1186/s40733-015-0001-7

relation: http://d-scholarship-dev.library.pitt.edu/25170/
title: Capturing the contribution of subject librarians applying strategy maps and balanced scorecards to liaison work
creator: Corrall, S
description: Purpose – The strategic contribution of subject librarians as information specialists in the digital world has been questioned by institutional administrators, but others have identified expanded roles and new opportunities in learning and research support. The purpose of this paper is to investigate the application of Kaplan and Norton’s strategic management system of balanced scorecards and strategy maps to subject librarianship in universities, with particular reference to the intellectual capital represented and created in the structures, relationships, and know-how of liaison work. Design/methodology/approach – A literature review was used to define established and emergent roles, responsibilities and skillsets of subject librarians, including their reach beyond the library. A web site survey investigated goals, actions, and values related to liaison work in UK library strategies. Data were analyzed thematically to develop an exemplar map and assess its potential for evaluating the contribution of subject librarians. Findings – Core functions continue, with expanded scope and competencies. Collaboration and integrated services are key trends for mapping. Liaison work is poorly documented in existing strategies. Preliminary results suggest that strategy maps can be used to illustrate the strategic contribution of subject librarians. Research limitations/implications – The paper reports the early stages of a multi-phase project. The results are limited to the conceptual phase. The next phase will explore the development of both maps and balanced scorecards via case studies in different countries. Originality/value – There are few examples of library applications of strategy maps and balanced scorecards at unit or program level, and none with a focus on the intangible assets of subject librarians.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25170/1/Corrall_%282015%29_Lib_Mgmt_e-print.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25170/4/licence.txt
identifier:   Corrall, S  (2015) Capturing the contribution of subject librarians applying strategy maps and balanced scorecards to liaison work.  Library Management, 36 (3).  223 - 234.  ISSN 0143-5124     
relation: 10.1108/LM-09-2014-0101

relation: http://d-scholarship-dev.library.pitt.edu/28577/
title: Catch Me If You Can: The Link between Autophagy and Viruses
creator: Lennemann, NJ
creator: Coyne, CB
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28577/1/journal.ppat.1004685.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28577/3/licence.txt
identifier:   Lennemann, NJ and Coyne, CB  (2015) Catch Me If You Can: The Link between Autophagy and Viruses.  PLoS Pathogens, 11 (3).  1 - 6.  ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004685

relation: http://d-scholarship-dev.library.pitt.edu/24133/
title: Changes in carbon electrode morphology affect microbial fuel cell performance with Shewanella oneidensis MR-1
creator: Sanchez, DVP
creator: Jacobs, D
creator: Gregory, K
creator: Huang, J
creator: Hu, Y
creator: Vidic, R
creator: Yun, M
description: The formation of biofilm-electrodes is crucial for microbial fuel cell current production because optimal performance is often associated with thick biofilms. However, the influence of the electrode structure and morphology on biofilm formation is only beginning to be investigated. This study provides insight on how changing the electrode morphology affects current production of a pure culture of anode-respiring bacteria. Specifically, an analysis of the effects of carbon fiber electrodes with drastically different morphologies on biofilm formation and anode respiration by a pure culture (Shewanella oneidensis MR-1) were examined. Results showed that carbon nanofiber mats had -10 fold higher current than plain carbon microfiber paper and that the increase was not due to an increase in electrode surface area, conductivity, or the size of the constituent material. Cyclic voltammograms reveal that electron transfer from the carbon nanofiber mats was biofilm-based suggesting that decreasing the diameter of the constituent carbon material from a few microns to a few hundred nanometers is beneficial for electricity production solely because the electrode surface creates a more relevant mesh for biofilm formation by Shewanella oneidensis MR-1.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24133/1/energies-08-01817_%281%29.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24133/4/licence.txt
identifier:   Sanchez, DVP and Jacobs, D and Gregory, K and Huang, J and Hu, Y and Vidic, R and Yun, M  (2015) Changes in carbon electrode morphology affect microbial fuel cell performance with Shewanella oneidensis MR-1.  Energies, 8 (3).  1817 - 1829.      
relation: 10.3390/en8031817

relation: http://d-scholarship-dev.library.pitt.edu/26172/
title: Classroom writing tasks and students' analytic text-based writing
creator: Matsumura, LC
creator: Correnti, R
creator: Wang, E
description: The Common Core State Standards emphasize students writing analytically in response to texts. Questions remain about the nature of instruction that develops students' text- based writing skills. In the present study, we examined the role that writing task quality plays in students' mastery of analytic text- based writing. Text- based writing tasks (N = 149) were collected from 27 fifth- grade teachers in an urban district, and teachers completed daily surveys (i.e., instructional logs) to assess the frequency of their reading and writing instruction (30-45 days total). Students (N = 793) completed a performance assessment of their text- based writing skills. Results showed that the large majority of writing tasks guided students to retrieve isolated facts or engage with surface- level features of texts in their writing (i.e., were of a low level of cognitive demand). The cognitive demand of text- based writing assignments predicted multiple features of students' writing performance, including students' ability to reason analytically about texts (effect size [ES] = .46), use evidence to support their claims (ES = .46), and organize their writing (ES = .35), even after controlling for other dimensions of literacy instruction. The quality (grist) of text to which students responded predicted one dimension of students' writing performance, use of evidence to support their claims (ES = .37). Designing cognitively demanding text- based tasks should be considered an essential part of writing instruction reform and professional development programs for teachers that aim to increase students writing skills aligned to the Common Core.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26172/1/licence.txt
identifier:   Matsumura, LC and Correnti, R and Wang, E  (2015) Classroom writing tasks and students' analytic text-based writing.  Reading Research Quarterly, 50 (4).  417 - 438.  ISSN 0034-0553     
relation: 10.1002/rrq.110

relation: http://d-scholarship-dev.library.pitt.edu/24082/
title: Compartment-Specific and Sequential Role of MyD88 and CARD9 in Chemokine Induction and Innate Defense during Respiratory Fungal Infection
creator: Jhingran, A
creator: Kasahara, S
creator: Shepardson, KM
creator: Junecko, BAF
creator: Heung, LJ
creator: Kumasaka, DK
creator: Knoblaugh, SE
creator: Lin, X
creator: Kazmierczak, BI
creator: Reinhart, TA
creator: Cramer, RA
creator: Hohl, TM
description: Aspergillus fumigatus forms ubiquitous airborne conidia that humans inhale on a daily basis. Although respiratory fungal infection activates the adaptor proteins CARD9 and MyD88 via C-type lectin, Toll-like, and interleukin-1 family receptor signals, defining the temporal and spatial pattern of MyD88- and CARD9-coupled signals in immune activation and fungal clearance has been difficult to achieve. Herein, we demonstrate that MyD88 and CARD9 act in two discrete phases and in two cellular compartments to direct chemokine- and neutrophil-dependent host defense. The first phase depends on MyD88 signaling because genetic deletion of MyD88 leads to delayed induction of the neutrophil chemokines CXCL1 and CXCL5, delayed neutrophil lung trafficking, and fatal pulmonary damage at the onset of respiratory fungal infection. MyD88 expression in lung epithelial cells restores rapid chemokine induction and neutrophil recruitment via interleukin-1 receptor signaling. Exogenous CXCL1 administration reverses murine mortality in MyD88-deficient mice. The second phase depends predominately on CARD9 signaling because genetic deletion of CARD9 in radiosensitive hematopoietic cells interrupts CXCL1 and CXCL2 production and lung neutrophil recruitment beyond the initial MyD88-dependent phase. Using a CXCL2 reporter mouse, we show that lung-infiltrating neutrophils represent the major cellular source of CXCL2 during CARD9-dependent recruitment. Although neutrophil-intrinsic MyD88 and CARD9 function are dispensable for neutrophil conidial uptake and killing in the lung, global deletion of both adaptor proteins triggers rapidly progressive invasive disease when mice are challenged with an inoculum that is sub-lethal for single adapter protein knockout mice. Our findings demonstrate that distinct signal transduction pathways in the respiratory epithelium and hematopoietic compartment partially overlap to ensure optimal chemokine induction, neutrophil recruitment, and fungal clearance within the respiratory tract.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24082/1/journal.ppat.1004589.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24082/4/licence.txt
identifier:   Jhingran, A and Kasahara, S and Shepardson, KM and Junecko, BAF and Heung, LJ and Kumasaka, DK and Knoblaugh, SE and Lin, X and Kazmierczak, BI and Reinhart, TA and Cramer, RA and Hohl, TM  (2015) Compartment-Specific and Sequential Role of MyD88 and CARD9 in Chemokine Induction and Innate Defense during Respiratory Fungal Infection.  PLoS Pathogens, 11 (1).  1 - 22.  ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004589

relation: http://d-scholarship-dev.library.pitt.edu/24689/
title: Cortical inputs to the middle temporal visual area in New World owl monkeys
creator: Cerkevich, CM
creator: Collins, CE
creator: Kaas, JH
description: We made eight retrograde tracer injections into the middle temporal visual area (MT) of three New World owl monkeys (Aotus nancymaae). These injections were placed across the representation of the retina in MT to allow us to compare the locations of labeled cells in other areas in order to provide evidence for any retinotopic organization in those areas. Four regions projected to MT: 1) early visual areas, including V1, V2, V3, the dorsolateral visual area, and the dorsomedial visual area, provided topographically organized inputs to MT; 2) all areas in the MT complex (the middle temporal crescent, the middle superior temporal area, and the fundal areas of the superior temporal sulcus) projected to MT. Somewhat variably across injections, neurons were labeled in other parts of the temporal lobe; 3) regions in the location of the medial visual area, the posterior parietal cortex, and the lateral sulcus provided other inputs to MT; 4) finally, projections from the frontal eye field, frontal visual field, and prefrontal cortex were also labeled by our injections. These results further establish the sources of input to MT, and provide direct evidence within and across cases for retinotopic patterns of projections from early visual areas to MT.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24689/1/EB-69713-cortical-inputs-to-area-mt-in-new-world-owl-monkeys_122314.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24689/4/licence.txt
identifier:   Cerkevich, CM and Collins, CE and Kaas, JH  (2015) Cortical inputs to the middle temporal visual area in New World owl monkeys.  Eye and Brain, 7.  1 - 15.  ISSN 1179-2744     
relation: 10.2147/EB.S69713

relation: http://d-scholarship-dev.library.pitt.edu/25451/
title: Deferred lightweight indexing for log-structured key-value stores
creator: Tang, Y
creator: Iyengar, A
creator: Tan, W
creator: Fong, L
creator: Liu, L
creator: Palanisamy, B
description: The recent shift towards write-intensive workload on bigdata (e.g., financial trading, social user-generated data streams)has pushed the proliferation of log-structured key-value stores, represented by Google's BigTable [1], Apache HBase [2] andCassandra [3]. While providing key-based data access with aPut/Get interface, these key-value stores do not support value-based access methods, which significantly limits their applicability in modern web and database applications. In this paper, we present DELI, a DEferred Lightweight Indexing scheme on the log-structured key-value stores. To index intensively updated bigdata in real time, DELI aims at making the index maintenance as lightweight as possible. The key idea is to apply an append-only design for online index maintenance and to collect index garbage at carefully chosen time. DELI optimizes the performance of index garbage collection through tightly coupling its execution with a native routine process called compaction. The DELI'ssystem design is fault-tolerant and generic (to most key-valuestores), we implemented a prototype of DELI based on HBasewithout internal code modification. Our experiments show that the DELI offers significant performance advantage for the write-intensive index maintenance.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25451/1/Deli-ccgrid15.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25451/4/licence.txt
identifier:   Tang, Y and Iyengar, A and Tan, W and Fong, L and Liu, L and Palanisamy, B  (2015) Deferred lightweight indexing for log-structured key-value stores.  Proceedings - 2015 IEEE/ACM 15th International Symposium on Cluster, Cloud, and Grid Computing, CCGrid 2015.  11 - 20.      
relation: 10.1109/CCGrid.2015.150

relation: http://d-scholarship-dev.library.pitt.edu/28524/
title: Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila
creator: Yuva-Aydemir, Y
creator: Xu, XL
creator: Aydemir, O
creator: Gascon, E
creator: Sayin, S
creator: Zhou, W
creator: Hong, Y
creator: Gao, FB
description: Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3’UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous role for these miRNAs in maintaining neuroblast self-renewal through inhibiting premature differentiation. We also show that miR-92a and miR-92b directly target jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are partially rescued by reducing the level of jigr1. These results reveal a novel function of the miR-92 family in Drosophila neuroblasts and provide another example that local negative feedback regulation of host genes by intragenic miRNAs is essential for animal development.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28524/1/journal.pgen.1005264.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28524/3/licence.txt
identifier:   Yuva-Aydemir, Y and Xu, XL and Aydemir, O and Gascon, E and Sayin, S and Zhou, W and Hong, Y and Gao, FB  (2015) Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila.  PLoS Genetics, 11 (5).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005264

relation: http://d-scholarship-dev.library.pitt.edu/28515/
title: Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity
creator: Egan, P
creator: Moore, J
creator: Schunn, C
creator: Cagan, J
creator: LeDuc, P
description: In complex systems with stochastic components, systems laws often emerge that describe higher level behavior regardless of lower level component configurations. In this paper, emergent laws for describing mechanochemical systems are investigated for processive myosin-actin motility systems. On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption. Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements. It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed. The finding of such laws provides insight for how patterns emerge in stochastic mechanochemical systems, while also informing understanding and engineering of complex biological systems.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28515/1/journal.pcbi.1004177.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28515/3/licence.txt
identifier:   Egan, P and Moore, J and Schunn, C and Cagan, J and LeDuc, P  (2015) Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity.  PLoS Computational Biology, 11 (4).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004177

relation: http://d-scholarship-dev.library.pitt.edu/29135/
title: Enhancement of COPD biological networks using a web-based collaboration interface
creator: Boué, S
creator: Fields, B
creator: Hoeng, J
creator: Park, J
creator: Peitsch, MC
creator: Schlage, WK
creator: Talikka, M
creator: Binenbaum, I
creator: Bondarenko, V
creator: Bulgakov, OV
creator: Cherkasova, V
creator: Diaz-Diaz, N
creator: Fedorova, L
creator: Guryanova, S
creator: Guzova, J
creator: Igorevna Koroleva, G
creator: Kozhemyakina, E
creator: Kumar, R
creator: Lavid, N
creator: Lu, Q
creator: Menon, S
creator: Ouliel, Y
creator: Peterson, SC
creator: Prokhorov, A
creator: Sanders, E
creator: Schrier, S
creator: Schwaitzer Neta, G
creator: Shvydchenko, I
creator: Tallam, A
creator: Villa-Fombuena, G
creator: Wu, J
creator: Yudkevich, I
creator: Zelikman, M
description: The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29135/1/67738375-6381-425c-b05e-c8ac96340a13_5984_-_stephanie_boue_v2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29135/7/licence.txt
identifier:   Boué, S and Fields, B and Hoeng, J and Park, J and Peitsch, MC and Schlage, WK and Talikka, M and Binenbaum, I and Bondarenko, V and Bulgakov, OV and Cherkasova, V and Diaz-Diaz, N and Fedorova, L and Guryanova, S and Guzova, J and Igorevna Koroleva, G and Kozhemyakina, E and Kumar, R and Lavid, N and Lu, Q and Menon, S and Ouliel, Y and Peterson, SC and Prokhorov, A and Sanders, E and Schrier, S and Schwaitzer Neta, G and Shvydchenko, I and Tallam, A and Villa-Fombuena, G and Wu, J and Yudkevich, I and Zelikman, M  (2015) Enhancement of COPD biological networks using a web-based collaboration interface.  F1000Research, 4.   ISSN 2046-1402     
relation: 10.12688/f1000research.5984.2

relation: http://d-scholarship-dev.library.pitt.edu/28510/
title: Establishing a Statistical Link between Network Oscillations and Neural Synchrony
creator: Zhou, P
creator: Burton, SD
creator: Snyder, AC
creator: Smith, MA
creator: Urban, NN
creator: Kass, RE
description: Pairs of active neurons frequently fire action potentials or “spikes” nearly synchronously (i.e., within 5 ms of each other). This spike synchrony may occur by chance, based solely on the neurons’ fluctuating firing patterns, or it may occur too frequently to be explicable by chance alone. When spike synchrony above chances levels is present, it may subserve computation for a specific cognitive process, or it could be an irrelevant byproduct of such computation. Either way, spike synchrony is a feature of neural data that should be explained. A point process regression framework has been developed previously for this purpose, using generalized linear models (GLMs). In this framework, the observed number of synchronous spikes is compared to the number predicted by chance under varying assumptions about the factors that affect each of the individual neuron’s firing-rate functions. An important possible source of spike synchrony is network-wide oscillations, which may provide an essential mechanism of network information flow. To establish the statistical link between spike synchrony and network-wide oscillations, we have integrated oscillatory field potentials into our point process regression framework. We first extended a previously-published model of spike-field association and showed that we could recover phase relationships between oscillatory field potentials and firing rates. We then used this new framework to demonstrate the statistical relationship between oscillatory field potentials and spike synchrony in: 1) simulated neurons, 2) in vitro recordings of hippocampal CA1 pyramidal cells, and 3) in vivo recordings of neocortical V4 neurons. Our results provide a rigorous method for establishing a statistical link between network oscillations and neural synchrony.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28510/1/journal.pcbi.1004549.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28510/3/licence.txt
identifier:   Zhou, P and Burton, SD and Snyder, AC and Smith, MA and Urban, NN and Kass, RE  (2015) Establishing a Statistical Link between Network Oscillations and Neural Synchrony.  PLoS Computational Biology, 11 (10).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004549

relation: http://d-scholarship-dev.library.pitt.edu/28526/
title: The Evolutionary Origination and Diversification of a Dimorphic Gene Regulatory Network through Parallel Innovations in cis and trans
creator: Camino, EM
creator: Butts, JC
creator: Ordway, A
creator: Vellky, JE
creator: Rebeiz, M
creator: Williams, TM
description: The origination and diversification of morphological characteristics represents a key problem in understanding the evolution of development. Morphological traits result from gene regulatory networks (GRNs) that form a web of transcription factors, which regulate multiple cis-regulatory element (CRE) sequences to control the coordinated expression of differentiation genes. The formation and modification of GRNs must ultimately be understood at the level of individual regulatory linkages (i.e., transcription factor binding sites within CREs) that constitute the network. Here, we investigate how elements within a network originated and diversified to generate a broad range of abdominal pigmentation phenotypes among Sophophora fruit flies. Our data indicates that the coordinated expression of two melanin synthesis enzymes, Yellow and Tan, recently evolved through novel CRE activities that respond to the spatial patterning inputs of Hox proteins and the sex-specific input of Bric-à-brac transcription factors. Once established, it seems that these newly evolved activities were repeatedly modified by evolutionary changes in the network’s trans-regulators to generate large-scale changes in pigment pattern. By elucidating how yellow and tan are connected to the web of abdominal trans-regulators, we discovered that the yellow and tan abdominal CREs are composed of distinct regulatory inputs that exhibit contrasting responses to the same Hox proteins and Hox cofactors. These results provide an example in which CRE origination underlies a recently evolved novel trait, and highlights how coordinated expression patterns can evolve in parallel through the generation of unique regulatory linkages.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28526/1/journal.pgen.1005136.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28526/3/licence.txt
identifier:   Camino, EM and Butts, JC and Ordway, A and Vellky, JE and Rebeiz, M and Williams, TM  (2015) The Evolutionary Origination and Diversification of a Dimorphic Gene Regulatory Network through Parallel Innovations in cis and trans.  PLoS Genetics, 11 (4).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005136

relation: http://d-scholarship-dev.library.pitt.edu/24095/
title: Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks
creator: Priedigkeit, N
creator: Wolfe, N
creator: Clark, NL
description: Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC), is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting “disease map” network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24095/1/journal.pgen.1004967.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24095/4/licence.txt
identifier:   Priedigkeit, N and Wolfe, N and Clark, NL  (2015) Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks.  PLoS Genetics, 11 (2).  1 - 17.  ISSN 1553-7390     
relation: 10.1371/journal.pgen.1004967

relation: http://d-scholarship-dev.library.pitt.edu/28522/
title: Genetic Changes to a Transcriptional Silencer Element Confers Phenotypic Diversity within and between Drosophila Species
creator: Johnson, WC
creator: Ordway, AJ
creator: Watada, M
creator: Pruitt, JN
creator: Williams, TM
creator: Rebeiz, M
description: The modification of transcriptional regulation has become increasingly appreciated as a major contributor to morphological evolution. However, the role of negative-acting control elements (e.g. silencers) in generating morphological diversity has been generally overlooked relative to positive-acting “enhancer” elements. The highly variable body coloration patterns among Drosophilid insects represents a powerful model system in which the molecular alterations that underlie phenotypic diversity can be defined. In a survey of pigment phenotypes among geographically disparate Japanese populations of Drosophila auraria, we discovered a remarkable degree of variation in male-specific abdominal coloration. In testing the expression patterns of the major pigment-producing enzymes, we found that phenotypes uniquely correlated with differences in the expression of ebony, a gene required for yellow-colored cuticle. Assays of ebony’s transcriptional control region indicated that a lightly pigmented strain harbored cis-regulatory mutations that caused correlated changes in its expression. Through a series of chimeric reporter constructs between light and dark strain alleles, we localized function-altering mutations to a conserved silencer that mediates a male-specific pattern of ebony repression. This suggests that the light allele was derived through the loss of this silencer’s activity. Furthermore, examination of the ebony gene of D. serrata, a close relative of D. auraria which secondarily lost male-specific pigmentation revealed the parallel loss of this silencer element. These results demonstrate how loss-of-function mutations in a silencer element resulted in increased gene expression. We propose that the mutational inactivation of silencer elements may represent a favored path to evolve gene expression, impacting morphological traits.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28522/1/journal.pgen.1005279.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28522/3/licence.txt
identifier:   Johnson, WC and Ordway, AJ and Watada, M and Pruitt, JN and Williams, TM and Rebeiz, M  (2015) Genetic Changes to a Transcriptional Silencer Element Confers Phenotypic Diversity within and between Drosophila Species.  PLoS Genetics, 11 (6).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005279

relation: http://d-scholarship-dev.library.pitt.edu/22857/
title: Going along versus getting it right: The role of self-integrity in political conformity
creator: Binning, KR
creator: Brick, C
creator: Cohen, GL
creator: Sherman, DK
description: People often conform to the opinions of ingroup members, even when available evidence suggests that the group is misinformed. Following insights from the social identity approach and self-affirmation theory, it was hypothesized that people conform to salient opinions in an effort to maintain global self-integrity. In a series of experiments examining Americans' approval of President Obama and his policies, approval was consistently swayed by normative information (national polling data) but not by evidentiary information (indicators of national economic health), except under theory-predicted conditions. When participants had satisfied their sense of self-integrity with a self-affirmation exercise (Democrats in Study 1, Republicans in Study 2), or when they had low levels of American identification and thus were less concerned with national norms (Democrats and Republicans in Study 3), they showed the opposite pattern and were swayed by evidence in spite of contradicting normative information. The extent to which people are influenced by norms versus evidence in political judgment is shaped by social identity, one aspect of self-integrity. The results highlight a social psychological means to attenuate and potentially reverse conformity in the face of contradicting evidence, a finding with both practical and theoretical implications.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22857/1/political_conformity_JESP_inpress.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22857/8/licence.txt
identifier:   Binning, KR and Brick, C and Cohen, GL and Sherman, DK  (2015) Going along versus getting it right: The role of self-integrity in political conformity.  Journal of Experimental Social Psychology, 56.  73 - 88.  ISSN 0022-1031     
relation: 10.1016/j.jesp.2014.08.008

relation: http://d-scholarship-dev.library.pitt.edu/29126/
title: Histamine-2 receptor antagonists versus proton pump inhibitors for stress ulcer prophylaxis in the ICU
creator: Kahn, J
creator: Kopterides, P
description: An evaluation of a recent study by MacLaren R, Reynolds PM, Allen RR et al: Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit.
date: 2015-01-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29126/1/10.12688_f1000research.6813.1_20151120.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29126/7/licence.txt
identifier:   Kahn, J and Kopterides, P  (2015) Histamine-2 receptor antagonists versus proton pump inhibitors for stress ulcer prophylaxis in the ICU.  F1000Research, 4.   ISSN 2046-1402     
relation: 10.12688/f1000research.6813.1

relation: http://d-scholarship-dev.library.pitt.edu/28569/
title: Human Metapneumovirus Is Capable of Entering Cells by Fusion with Endosomal Membranes
creator: Cox, RG
creator: Mainou, BA
creator: Johnson, M
creator: Hastings, AK
creator: Schuster, JE
creator: Dermody, TS
creator: Williams, JV
description: Human metapneumovirus (HMPV), a member of the Paramyxoviridae family, is a leading cause of lower respiratory illness. Although receptor binding is thought to initiate fusion at the plasma membrane for paramyxoviruses, the entry mechanism for HMPV is largely uncharacterized. Here we sought to determine whether HMPV initiates fusion at the plasma membrane or following internalization. To study the HMPV entry process in human bronchial epithelial (BEAS-2B) cells, we used fluorescence microscopy, an R18-dequenching fusion assay, and developed a quantitative, fluorescence microscopy assay to follow virus binding, internalization, membrane fusion, and visualize the cellular site of HMPV fusion. We found that HMPV particles are internalized into human bronchial epithelial cells before fusing with endosomes. Using chemical inhibitors and RNA interference, we determined that HMPV particles are internalized via clathrin-mediated endocytosis in a dynamin-dependent manner. HMPV fusion and productive infection are promoted by RGD-binding integrin engagement, internalization, actin polymerization, and dynamin. Further, HMPV fusion is pH-independent, although infection with rare strains is modestly inhibited by RNA interference or chemical inhibition of endosomal acidification. Thus, HMPV can enter via endocytosis, but the viral fusion machinery is not triggered by low pH. Together, our results indicate that HMPV is capable of entering host cells by multiple pathways, including membrane fusion from endosomal compartments.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28569/1/journal.ppat.1005303.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28569/3/licence.txt
identifier:   Cox, RG and Mainou, BA and Johnson, M and Hastings, AK and Schuster, JE and Dermody, TS and Williams, JV  (2015) Human Metapneumovirus Is Capable of Entering Cells by Fusion with Endosomal Membranes.  PLoS Pathogens, 11 (12).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1005303

relation: http://d-scholarship-dev.library.pitt.edu/25501/
title: The Hypnerotomachia Poliphili and Italian art circa 1500: Mantegna, Antico, and Correggio
creator: Nygren, CJ
description: This essay focuses on the interplay between the Hypnerotomachia Poliphili and Italian art of the early sixteenth century. While the Hypnerotomachia exerted some influence on artists of the subsequent generation, the nature of that influence will be reevaluated in light of the functions that poetic favole accrued around the turn of the sixteenth century. Opening with an examination of two paintings by Antonio Allegri da Correggio that are often seen as illustrative of the impact that the Hypnerotomachia had on Italian art, this essay will subsequently open up distance between the pictures and their purported source text. Focusing attention on Correggio's complex engagement with the Hypnerotomachia affords new insights into the intricacy of the text itself, its relationship with antiquity, and how the tension between these two elements helped shape the anomalous status the Hypnerotomachia occupies today. The peculiar antiquarian approach that the Hypnerotomachia takes toward the study of language, architecture, and artifacts was quite common throughout the fifteenth century, but it quickly fell out of favor in the sixteenth century. The article concludes by suggesting that art historians begin thinking of the Hypnerotomachia as the extended manifesto of a model of engaged beholdership that held currency in Northern Italy around 1500 rather than as a source for iconography and new subjects. Viewed in this light, Colonna's text yields important insights into the alluring qualities of artists like Mantegna and Antico, who shared with the Hypnerotomachia an abiding interest in interrogating antiquity as one of the animating forces underwriting their artistic project.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25501/1/licence.txt
identifier:   Nygren, CJ  (2015) The Hypnerotomachia Poliphili and Italian art circa 1500: Mantegna, Antico, and Correggio.  Word and Image, 31 (2).  140 - 154.  ISSN 0266-6286     
relation: 10.1080/02666286.2015.1023020

relation: http://d-scholarship-dev.library.pitt.edu/28575/
title: An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons
creator: Markus, A
creator: Lebenthal-Loinger, I
creator: Yang, IH
creator: Kinchington, PR
creator: Goldstein, RS
description: Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28575/1/journal.ppat.1004885.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28575/3/licence.txt
identifier:   Markus, A and Lebenthal-Loinger, I and Yang, IH and Kinchington, PR and Goldstein, RS  (2015) An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons.  PLoS Pathogens, 11 (6).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004885

relation: http://d-scholarship-dev.library.pitt.edu/32687/
title: Individual differences in toddlers' social understanding and prosocial behavior: Disposition or socialization?
creator: Gross, RL
creator: Drummond, J
creator: Satlof-Bedrick, E
creator: Waugh, WE
creator: Svetlova, M
creator: Brownell, CA
description: We examined how individual differences in social understanding contribute to variability in early-appearing prosocial behavior. Moreover, potential sources of variability in social understanding were explored and examined as additional possible predictors of prosocial behavior. Using a multi-method approach with both observed and parent-report measures, 325 children aged 18-30 months were administered measures of social understanding (e.g., use of emotion words; self-understanding), prosocial behavior (in separate tasks measuring instrumental helping, empathic helping, and sharing, as well as parent-reported prosociality at home), temperament (fearfulness, shyness, and social fear), and parental socialization of prosocial behavior in the family. Individual differences in social understanding predicted variability in empathic helping and parent-reported prosociality, but not instrumental helping or sharing. Parental socialization of prosocial behavior was positively associated with toddlers' social understanding, prosocial behavior at home, and instrumental helping in the lab, and negatively associated with sharing (possibly reflecting parents' increased efforts to encourage children who were less likely to share). Further, socialization moderated the association between social understanding and prosocial behavior, such that social understanding was less predictive of prosocial behavior among children whose parents took a more active role in socializing their prosociality. None of the dimensions of temperament was associated with either social understanding or prosocial behavior. Parental socialization of prosocial behavior is thus an important source of variability in children's early prosociality, acting in concert with early differences in social understanding, with different patterns of influence for different subtypes of prosocial behavior.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32687/1/fpsyg-06-00600.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/32687/7/licence.txt
identifier:   Gross, RL and Drummond, J and Satlof-Bedrick, E and Waugh, WE and Svetlova, M and Brownell, CA  (2015) Individual differences in toddlers' social understanding and prosocial behavior: Disposition or socialization?  Frontiers in Psychology, 6 (MAY).       
relation: 10.3389/fpsyg.2015.00600

relation: http://d-scholarship-dev.library.pitt.edu/4018/
title: Introduction
creator: Infanti, AC
date: 2015-01-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/4018/1/31735062115930.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/4018/8/licence.txt
identifier:   Infanti, AC  (2015) Introduction.         

relation: http://d-scholarship-dev.library.pitt.edu/28571/
title: A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling
creator: Hu, M
creator: Wang, C
creator: Li, W
creator: Lu, W
creator: Bai, Z
creator: Qin, D
creator: Yan, Q
creator: Zhu, J
creator: Krueger, BJ
creator: Renne, R
creator: Gao, SJ
creator: Lu, C
description: Kaposi's sarcoma (KS) is a highly disseminated angiogenic tumor of endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV encodes more than two dozens of miRNAs but their roles in KSHV-induced tumor dissemination and metastasis remain unknown. Here, we found that ectopic expression of miR-K12-3 (miR-K3) promoted endothelial cell migration and invasion. Bioinformatics and luciferase reporter analyses showed that miR-K3 directly targeted G protein-coupled receptor (GPCR) kinase 2 (GRK2, official gene symbol ADRBK1). Importantly, overexpression of GRK2 reversed miR-K3 induction of cell migration and invasion. Furthermore, the chemokine receptor CXCR2, which was negatively regulated by GRK2, was upregulated in miR-K3-transduced endothelial cells. Knock down of CXCR2 abolished miR-K3-induced cell migration and invasion. Moreover, miR-K3 downregulation of GRK2 relieved its direct inhibitory effect on AKT. Both CXCR2 induction and the release of AKT from GRK2 were required for miR-K3 maximum activation of AKT and induction of cell migration and invasion. Finally, deletion of miR-K3 from the KSHV genome abrogated its effect on the GRK2/CXCR2/AKT pathway and KSHV-induced migration and invasion. Our data provide the first-line evidence that, by repressing GRK2, miR-K3 facilitates cell migration and invasion via activation of CXCR2/AKT signaling, which likely contribute to the dissemination of KSHV-induced tumors.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28571/1/journal.ppat.1005171.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28571/3/licence.txt
identifier:   Hu, M and Wang, C and Li, W and Lu, W and Bai, Z and Qin, D and Yan, Q and Zhu, J and Krueger, BJ and Renne, R and Gao, SJ and Lu, C  (2015) A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling.  PLoS Pathogens, 11 (9).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1005171

relation: http://d-scholarship-dev.library.pitt.edu/29430/
title: Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer
creator: Sun, Y
creator: Guo, F
creator: Bagnoli, M
creator: Xue, FX
creator: Sun, BC
creator: Shmulevich, I
creator: Mezzanzanica, D
creator: Chen, KX
creator: Sood, AK
creator: Yang, D
creator: Zhang, W
description: Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29430/1/art%253A10.5732%252Fcjc.014.10284.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29430/7/licence.txt
identifier:   Sun, Y and Guo, F and Bagnoli, M and Xue, FX and Sun, BC and Shmulevich, I and Mezzanzanica, D and Chen, KX and Sood, AK and Yang, D and Zhang, W  (2015) Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer.  Chinese Journal of Cancer, 34 (1).  28 - 40.      
relation: 10.5732/cjc.014.10284

relation: http://d-scholarship-dev.library.pitt.edu/29396/
title: Knowledge, attitudes, and preferences of healthy young adults regarding advance care planning: A focus group study of university students in Pittsburgh, USA Health behavior, health promotion and society
creator: Kavalieratos, D
creator: Ernecoff, NC
creator: Keim-Malpass, J
creator: Degenholtz, HB
description: Background: To date, research and promotion regarding advance care planning (ACP) has targeted those with serious illness or the elderly, thereby ignoring healthy young adults. The purpose of this study was to explore young adults' knowledge, attitudes, and preferences regarding advance care planning (ACP) and medical decision-making. Further, we aimed to understand the potential role of public health to encourage population-based promotion of ACP. Methods: Between February 2007 and April 2007, we conducted six focus groups comprising 56 young adults ages 18-30. Topics explored included (1) baseline knowledge regarding ACP, (2) preferences for ACP, (3) characteristics of preferred surrogates, and (4) barriers and facilitators to completing ACP specific to age and individuation. We used a qualitative thematic approach to analyze transcripts. Results: All participants desired more information regarding ACP. In addition, participants expressed (1) heterogeneous attitudes regarding triggers to perform ACP, (2) the opinion that ACP is a marker of individuation, (3) the belief that prior exposure to illness plays a role in prompting ACP, and (4) an appreciation that ACP is flexible to changes in preferences and circumstances throughout the life-course. Conclusion: Young adults perceive ACP as a worthwhile health behavior and view a lack of information as a major barrier to discussion and adoption. Our data emphasize the need for strategies to increase ACP knowledge, while encouraging population-level, patient-centered, healthcare decision-making.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29396/1/art%253A10.1186%252Fs12889-015-1575-y.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29396/7/licence.txt
identifier:   Kavalieratos, D and Ernecoff, NC and Keim-Malpass, J and Degenholtz, HB  (2015) Knowledge, attitudes, and preferences of healthy young adults regarding advance care planning: A focus group study of university students in Pittsburgh, USA Health behavior, health promotion and society.  BMC Public Health, 15 (1).       
relation: 10.1186/s12889-015-1575-y

relation: http://d-scholarship-dev.library.pitt.edu/25531/
title: Learning discrete Bayesian network parameters from continuous data streams: What is the best strategy?
creator: Ratnapinda, P
creator: Druzdzel, MJ
description: We compare three approaches to learning numerical parameters of discrete Bayesian networks from continuous data streams: (1) the EM algorithm applied to all data, (2) the EM algorithm applied to data increments, and (3) the online EM algorithm. Our results show that learning from all data at each step, whenever feasible, leads to the highest parameter accuracy and model classification accuracy. When facing computational limitations, incremental learning approaches are a reasonable alternative. While the differences in speed between incremental algorithms are not large (online EM is slightly slower), for all but small data sets online EM tends to be more accurate than incremental EM.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25531/1/licence.txt
identifier:   Ratnapinda, P and Druzdzel, MJ  (2015) Learning discrete Bayesian network parameters from continuous data streams: What is the best strategy?  Journal of Applied Logic, 13 (4).  628 - 642.  ISSN 1570-8683     
relation: 10.1016/j.jal.2015.03.007

relation: http://d-scholarship-dev.library.pitt.edu/25279/
title: Lester J. Cappon and the publishing of modern documentary editions
creator: Cox, RJ
description: Documentary editing is a well-developed field connected to the historical and archival professions. It was not always so well established, as a study of Lester J. Cappon's career suggests. Between his work at the Institute of Early American History and Culture starting in the 1950s and his final years as a fellow at the Newberry Library, Cappon played an important role in nurturing documentary editing as a profession.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/msword
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25279/1/Cox_Cappon_as_Documentary_Editor.docx
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25279/3/licence.txt
identifier:   Cox, RJ  (2015) Lester J. Cappon and the publishing of modern documentary editions.  Journal of Scholarly Publishing, 46 (3).  224 - 250.  ISSN 1198-9742     
relation: 10.3138/jsp.46.3.02

relation: http://d-scholarship-dev.library.pitt.edu/28523/
title: Leveraging Identity-by-Descent for Accurate Genotype Inference in Family Sequencing Data
creator: Li, B
creator: Wei, Q
creator: Zhan, X
creator: Zhong, X
creator: Chen, W
creator: Li, C
creator: Haines, J
description: Sequencing family DNA samples provides an attractive alternative to population based designs to identify rare variants associated with human disease due to the enrichment of causal variants in pedigrees. Previous studies showed that genotype calling accuracy can be improved by modeling family relatedness compared to standard calling algorithms. Current family-based variant calling methods use sequencing data on single variants and ignore the identity-by-descent (IBD) sharing along the genome. In this study we describe a new computational framework to accurately estimate the IBD sharing from the sequencing data, and to utilize the inferred IBD among family members to jointly call genotypes in pedigrees. Through simulations and application to real data, we showed that IBD can be reliably estimated across the genome, even at very low coverage (e.g. 2X), and genotype accuracy can be dramatically improved. Moreover, the improvement is more pronounced for variants with low frequencies, especially at low to intermediate coverage (e.g. 10X to 20X), making our approach effective in studying rare variants in cost-effective whole genome sequencing in pedigrees. We hope that our tool is useful to the research community for identifying rare variants for human disease through family-based sequencing.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28523/1/journal.pgen.1005271.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28523/3/licence.txt
identifier:   Li, B and Wei, Q and Zhan, X and Zhong, X and Chen, W and Li, C and Haines, J  (2015) Leveraging Identity-by-Descent for Accurate Genotype Inference in Family Sequencing Data.  PLoS Genetics, 11 (6).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005271

relation: http://d-scholarship-dev.library.pitt.edu/26326/
title: Managing participation through modal affordances on Twitter
creator: Draucker, F
creator: Collister, L
description: On Twitter, retweets function as a method of reporting speech and spreading the talk of other users. We propose that changes to the interface and mechanisms of Twitter have led to the coexistence of two complementary forms of retweeting. The Preserving Retweet, enabled by the Twitter interface, directly reports speech and retains attribution to the original author, but it does not allow for any modification or indication of stance. The Adapting Retweet, a user-created norm studied by boyd et al. (2010), allows users the option to add comments to pre-existing tweets but resulting in confusion in attribution. Using an updated form of Goffman's participation framework, we analyze the use of these two types of retweets and their impact on attribution.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26326/1/draucker-collister-managingparticipation.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26326/4/licence.txt
identifier:   Draucker, F and Collister, L  (2015) Managing participation through modal affordances on Twitter.  Open Library of Humanities, 1 (1).       
relation: 10.16995/olh.21

relation: http://d-scholarship-dev.library.pitt.edu/29264/
title: MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxelbased therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603
creator: Villaruz, LC
creator: Huang, G
creator: Romkes, M
creator: Kirkwood, JM
creator: Buch, SC
creator: Nukui, T
creator: Flaherty, KT
creator: Lee, SJ
creator: Wilson, MA
creator: Nathanson, KL
creator: Benos, PV
creator: Tawbi, HA
description: Background: Carboplatin/paclitaxel (CP), with or without sorafenib, result in objective response rates of 18-20 % in unselected chemotherapy-naïve patients. Molecular predictors of survival and response to CP-based chemotherapy in metastatic melanoma (MM) are critical to improving the therapeutic index. Intergroup trial E2603 randomized MM patients to CP with or without sorafenib. Expression data were collected from pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor tissues from 115 of 823 patients enrolled on E2603. The selected patients were balanced across treatment arms, BRAF status, and clinical outcome. We generated data using Nanostring array (microRNA (miRNA) expression) and DNA-mediated annealing, selection, extension and ligation (DASL)/Illumina microarrays (HT12 v4) (mRNA expression) with protocols optimized for FFPE samples. Integrative computational analysis was performed using a novel Tree-guided Recursive Cluster Selection (T-ReCS) [1] algorithm to select the most informative features/genes, followed by TargetScan miRNA target prediction (Human v6.2) and mirConnX [2] for network inference. Results: T-ReCS identified PLXNB1 as negatively associated with progression-free survival (PFS) and miR-659-3p as the primary miRNA associated positively with PFS. miR-659-3p was differentially expressed based on PFS but not based on treatment arm, BRAF or NRAS status. Dichotomized by median PFS (less vs greater than 4 months), miR-659-3p expression was significantly different. High miR-659-3p expression distinguished patients with responsive disease (complete or partial response) from patients with stable disease. miR-659-3p predicted gene targets include NFIX, which is a transcription factor known to interact with c-Jun and AP-1 in the context of developmental processes and disease. Conclusions: This novel integrative analysis implicates miR-659-3p as a candidate predictive biomarker for MM patients treated with platinum-based chemotherapy and may serve to improve patient selection.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29264/1/art%253A10.1186%252Fs13148-015-0092-2.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29264/7/licence.txt
identifier:   Villaruz, LC and Huang, G and Romkes, M and Kirkwood, JM and Buch, SC and Nukui, T and Flaherty, KT and Lee, SJ and Wilson, MA and Nathanson, KL and Benos, PV and Tawbi, HA  (2015) MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxelbased therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603.  Clinical Epigenetics, 7 (1).   ISSN 1868-7075     
relation: 10.1186/s13148-015-0092-2

relation: http://d-scholarship-dev.library.pitt.edu/28509/
title: A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis
creator: Malkin, AD
creator: Sheehan, RP
creator: Mathew, S
creator: Federspiel, WJ
creator: Redl, H
creator: Clermont, G
description: Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8), a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3–6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40–80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5–24 hours, which may reduce survival to 13%. In severe sepsis, an extracorporeal treatment which modulates CXCR-1/2 levels has therapeutic potential, but also potential for harm. Further development of the computational model will help guide optimal device development and determine which patient populations should be targeted by treatment.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28509/1/journal.pcbi.1004314.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28509/3/licence.txt
identifier:   Malkin, AD and Sheehan, RP and Mathew, S and Federspiel, WJ and Redl, H and Clermont, G  (2015) A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.  PLoS Computational Biology, 11 (10).   ISSN 1553-734X     
relation: 10.1371/journal.pcbi.1004314

relation: http://d-scholarship-dev.library.pitt.edu/28521/
title: The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae
creator: Cucinotta, CE
creator: Young, AN
creator: Klucevsek, KM
creator: Arndt, KM
description: Eukaryotes regulate gene expression and other nuclear processes through the posttranslational modification of histones. In S. cerevisiae, the mono-ubiquitylation of histone H2B on lysine 123 (H2B K123ub) affects nucleosome stability, broadly influences gene expression and other DNA-templated processes, and is a prerequisite for additional conserved histone modifications that are associated with active transcription, namely the methylation of lysine residues in H3. While the enzymes that promote these chromatin marks are known, regions of the nucleosome required for the recruitment of these enzymes are undefined. To identify histone residues required for H2B K123ub, we exploited a functional interaction between the ubiquitin-protein ligase, Rkr1/Ltn1, and H2B K123ub in S. cerevisiae. Specifically, we performed a synthetic lethal screen with cells lacking RKR1 and a comprehensive library of H2A and H2B residue substitutions, and identified H2A residues that are required for H2B K123ub. Many of these residues map to the nucleosome acidic patch. The substitutions in the acidic patch confer varying histone modification defects downstream of H2B K123ub, indicating that this region contributes differentially to multiple histone modifications. Interestingly, substitutions in the acidic patch result in decreased recruitment of H2B K123ub machinery to active genes and defects in transcription elongation and termination. Together, our findings reveal a role for the nucleosome acidic patch in recruitment of histone modification machinery and maintenance of transcriptional integrity.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28521/1/journal.pgen.1005420.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28521/3/licence.txt
identifier:   Cucinotta, CE and Young, AN and Klucevsek, KM and Arndt, KM  (2015) The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae.  PLoS Genetics, 11 (8).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005420

relation: http://d-scholarship-dev.library.pitt.edu/25938/
title: Off the beaten path: The impact of adaptive content sequencing on student navigation in an open social student modeling interface
creator: Hosseini, R
creator: Hsiao, IH
creator: Guerra, J
creator: Brusilovsky, P
description: One of the original goals of intelligent educational systems is to guide every student to the most appropriate educational content. Exploring both knowledge-based and social guidance approaches in past work, we learned that each of these approaches has weak sides. In this paper we follow the idea of combining social guidance with more traditional knowledge-based guidance to support more optimal content navigation. We proposed a greedy sequencing approach that maximizes student’s level of knowledge and tested it in a classroom. Results indicated that this approach positively impacts students’ navigation.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25938/1/paper_183.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25938/4/licence.txt
identifier:   Hosseini, R and Hsiao, IH and Guerra, J and Brusilovsky, P  (2015) Off the beaten path: The impact of adaptive content sequencing on student navigation in an open social student modeling interface.  Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 9112.  624 - 628.  ISSN 0302-9743     
relation: 10.1007/978-3-319-19773-9_77

relation: http://d-scholarship-dev.library.pitt.edu/24683/
title: On conditions for unrectifiability of a metric space
creator: Hajłasz, P
creator: Malekzadeh, S
description: We find necessary and sufficient conditions for a Lipschitz map f : E Rk ! X into a metric space to satisfyHk(f (E)) = 0. An interesting feature of our approach is that despite the fact that we are dealing with arbitrary metric spaces, we employ a variant of the classical implicit function theorem. Applications include pure unrectifiability of the Heisenberg groups.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24683/1/agms-2015-0001.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24683/4/licence.txt
identifier:   Hajłasz, P and Malekzadeh, S  (2015) On conditions for unrectifiability of a metric space.  Analysis and Geometry in Metric Spaces, 3 (1).  1 - 14.      
relation: 10.1515/agms-2015-0001

relation: http://d-scholarship-dev.library.pitt.edu/28525/
title: Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape
creator: Hancks, DC
creator: Hartley, MK
creator: Hagan, C
creator: Clark, NL
creator: Elde, NC
description: A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular ‘arms races.’ Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2’-5’-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted to circumvent viral-encoded inhibitors.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28525/1/journal.pgen.1005203.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28525/3/licence.txt
identifier:   Hancks, DC and Hartley, MK and Hagan, C and Clark, NL and Elde, NC  (2015) Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.  PLoS Genetics, 11 (5).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1005203

relation: http://d-scholarship-dev.library.pitt.edu/28579/
title: P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy
creator: Sinadinos, A
creator: Young, CNJ
creator: Al-Khalidi, R
creator: Teti, A
creator: Kalinski, P
creator: Mohamad, S
creator: Floriot, L
creator: Henry, T
creator: Tozzi, G
creator: Jiang, T
creator: Wurtz, O
creator: Lefebvre, A
creator: Shugay, M
creator: Tong, J
creator: Vaudry, D
creator: Arkle, S
creator: doRego, JC
creator: Górecki, DC
description: Background: Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target. Methods and Findings: Using a combination of molecular, histological, and biochemical methods and behavioral analyses in vivo we demonstrate, to our knowledge for the first time, that genetic ablation of P2RX7 in the DMD model mouse produces a widespread functional attenuation of both muscle and non-muscle symptoms. In dystrophic muscles at 4 wk there was an evident recovery in key functional and molecular parameters such as improved muscle structure (minimum Feret diameter, p < 0.001), increased muscle strength in vitro (p < 0.001) and in vivo (p = 0.012), and pro-fibrotic molecular signatures. Serum creatine kinase (CK) levels were lower (p = 0.025), and reduced cognitive impairment (p = 0.006) and bone structure alterations (p < 0.001) were also apparent. Reduction of inflammation and fibrosis persisted at 20 mo in leg (p = 0.038), diaphragm (p = 0.042), and heart muscles (p < 0.001). We show that the amelioration of symptoms was proportional to the extent of receptor depletion and that improvements were observed following administration of two P2RX7 antagonists (CK, p = 0.030 and p = 0.050) without any detectable side effects. However, approaches successful in animal models still need to be proved effective in clinical practice. Conclusions: These results are, to our knowledge, the first to establish that a single treatment can improve muscle function both short and long term and also correct cognitive impairment and bone loss in DMD model mice. The wide-ranging improvements reflect the convergence of P2RX7 ablation on multiple disease mechanisms affecting skeletal and cardiac muscles, inflammatory cells, brain, and bone. Given the impact of P2RX7 blockade in the DMD mouse model, this receptor is an attractive target for translational research: existing drugs with established safety records could potentially be repurposed for treatment of this lethal disease.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28579/1/journal.pmed.1001888.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28579/3/licence.txt
identifier:   Sinadinos, A and Young, CNJ and Al-Khalidi, R and Teti, A and Kalinski, P and Mohamad, S and Floriot, L and Henry, T and Tozzi, G and Jiang, T and Wurtz, O and Lefebvre, A and Shugay, M and Tong, J and Vaudry, D and Arkle, S and doRego, JC and Górecki, DC  (2015) P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy.  PLoS Medicine, 12 (10).   ISSN 1549-1277     
relation: 10.1371/journal.pmed.1001888

relation: http://d-scholarship-dev.library.pitt.edu/29388/
title: Pass quantity, focus on quality
creator: Liu, D
creator: Sun, W
creator: Hou, J
creator: Yuan, R
creator: Li, Z
description: Journal of Hematology & Oncology is pleased to see the exponential growth in the number of publications from China, especially in hematology and oncology. This editorial calls for putting more weight on the quality of the future scientific output and invites rigorous dialogs among policy makers, granting agencies, academic leaders, physicians, and scientists, followed by concrete actions, to achieve such a goal.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29388/1/art%253A10.1186%252Fs13045-015-0123-7.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29388/7/licence.txt
identifier:   Liu, D and Sun, W and Hou, J and Yuan, R and Li, Z  (2015) Pass quantity, focus on quality.  Journal of Hematology and Oncology, 8 (1).       
relation: 10.1186/s13045-015-0123-7

relation: http://d-scholarship-dev.library.pitt.edu/29407/
title: Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies
creator: Samwald, M
creator: Giménez, JAM
creator: Boyce, RD
creator: Freimuth, RR
creator: Adlassnig, KP
creator: Dumontier, M
description: Background: Every year, hundreds of thousands of patients experience treatment failure or adverse drug reactions (ADRs), many of which could be prevented by pharmacogenomic testing. However, the primary knowledge needed for clinical pharmacogenomics is currently dispersed over disparate data structures and captured in unstructured or semi-structured formalizations. This is a source of potential ambiguity and complexity, making it difficult to create reliable information technology systems for enabling clinical pharmacogenomics. Methods: We developed Web Ontology Language (OWL) ontologies and automated reasoning methodologies to meet the following goals: 1) provide a simple and concise formalism for representing pharmacogenomic knowledge, 2) finde errors and insufficient definitions in pharmacogenomic knowledge bases, 3) automatically assign alleles and phenotypes to patients, 4) match patients to clinically appropriate pharmacogenomic guidelines and clinical decision support messages and 5) facilitate the detection of inconsistencies and overlaps between pharmacogenomic treatment guidelines from different sources. We evaluated different reasoning systems and test our approach with a large collection of publicly available genetic profiles. Results: Our methodology proved to be a novel and useful choice for representing, analyzing and using pharmacogenomic data. The Genomic Clinical Decision Support (Genomic CDS) ontology represents 336 SNPs with 707 variants; 665 haplotypes related to 43 genes; 22 rules related to drug-response phenotypes; and 308 clinical decision support rules. OWL reasoning identified CDS rules with overlapping target populations but differing treatment recommendations. Only a modest number of clinical decision support rules were triggered for a collection of 943 public genetic profiles. We found significant performance differences across available OWL reasoners. Conclusions: The ontology-based framework we developed can be used to represent, organize and reason over the growing wealth of pharmacogenomic knowledge, as well as to identify errors, inconsistencies and insufficient definitions in source data sets or individual patient data. Our study highlights both advantages and potential practical issues with such an ontology-based approach.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29407/1/art%253A10.1186%252Fs12911-015-0130-1.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29407/7/licence.txt
identifier:   Samwald, M and Giménez, JAM and Boyce, RD and Freimuth, RR and Adlassnig, KP and Dumontier, M  (2015) Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.  BMC Medical Informatics and Decision Making, 15 (1).       
relation: 10.1186/s12911-015-0130-1

relation: http://d-scholarship-dev.library.pitt.edu/24080/
title: Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine
creator: Craigo, JK
creator: Ezzelarab, C
creator: Cook, SJ
creator: Liu, C
creator: Horohov, D
creator: Issel, CJ
creator: Montelaro, RC
description: Lentiviral Envelope (Env) antigenic variation and related immune evasion present major hurdles to effective vaccine development. Centralized Env immunogens that minimize the genetic distance between vaccine proteins and circulating viral isolates are an area of increasing study in HIV vaccinology. To date, the efficacy of centralized immunogens has not been evaluated in the context of an animal model that could provide both immunogenicity and protective efficacy data. We previously reported on a live-attenuated (attenuated) equine infectious anemia (EIAV) virus vaccine, which provides 100% protection from disease after virulent, homologous, virus challenge. Further, protective efficacy demonstrated a significant, inverse, linear relationship between EIAV Env divergence and protection from disease when vaccinates were challenged with viral strains of increasing Env divergence from the vaccine strain Env. Here, we sought to comprehensively examine the protective efficacy of centralized immunogens in our attenuated vaccine platform. We developed, constructed, and extensively tested a consensus Env, which in a virulent proviral backbone generated a fully replication-competent pathogenic virus, and compared this consensus Env to an ancestral Env in our attenuated proviral backbone. A polyvalent attenuated vaccine was established for comparison to the centralized vaccines. Additionally, an engineered quasispecies challenge model was created for rigorous assessment of protective efficacy. Twenty-four EIAV-naïve animals were vaccinated and challenged along with six-control animals six months post-second inoculation. Pre-challenge data indicated the consensus Env was more broadly immunogenic than the Env of the other attenuated vaccines. However, challenge data demonstrated a significant increase in protective efficacy of the polyvalent vaccine. These findings reveal, for the first time, a consensus Env immunogen that generated a fully-functional, replication-competent lentivirus, which when experimentally evaluated, demonstrated broader immunogenicity that does not equate to higher protective efficacy.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24080/1/journal.ppat.1004610.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24080/4/licence.txt
identifier:   Craigo, JK and Ezzelarab, C and Cook, SJ and Liu, C and Horohov, D and Issel, CJ and Montelaro, RC  (2015) Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine.  PLoS Pathogens, 11 (1).  1 - 14.  ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004610

relation: http://d-scholarship-dev.library.pitt.edu/28576/
title: Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus Genomes
creator: Dembowski, JA
creator: DeLuca, NA
description: Much of the HSV-1 life cycle is carried out in the cell nucleus, including the expression, replication, repair, and packaging of viral genomes. Viral proteins, as well as cellular factors, play essential roles in these processes. Isolation of proteins on nascent DNA (iPOND) was developed to label and purify cellular replication forks. We adapted aspects of this method to label viral genomes to both image, and purify replicating HSV-1 genomes for the identification of associated proteins. Many viral and cellular factors were enriched on viral genomes, including factors that mediate DNA replication, repair, chromatin remodeling, transcription, and RNA processing. As infection proceeded, packaging and structural components were enriched to a greater extent. Among the more abundant proteins that copurified with genomes were the viral transcription factor ICP4 and the replication protein ICP8. Furthermore, all seven viral replication proteins were enriched on viral genomes, along with cellular PCNA and topoisomerases, while other cellular replication proteins were not detected. The chromatin-remodeling complexes present on viral genomes included the INO80, SWI/SNF, NURD, and FACT complexes, which may prevent chromatinization of the genome. Consistent with this conclusion, histones were not readily recovered with purified viral genomes, and imaging studies revealed an underrepresentation of histones on viral genomes. RNA polymerase II, the mediator complex, TFIID, TFIIH, and several other transcriptional activators and repressors were also affinity purified with viral DNA. The presence of INO80, NURD, SWI/SNF, mediator, TFIID, and TFIIH components is consistent with previous studies in which these complexes copurified with ICP4. Therefore, ICP4 is likely involved in the recruitment of these key cellular chromatin remodeling and transcription factors to viral genomes. Taken together, iPOND is a valuable method for the study of viral genome dynamics during infection and provides a comprehensive view of how HSV-1 selectively utilizes cellular resources.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28576/1/journal.ppat.1004939.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28576/3/licence.txt
identifier:   Dembowski, JA and DeLuca, NA  (2015) Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus Genomes.  PLoS Pathogens, 11 (5).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004939

relation: http://d-scholarship-dev.library.pitt.edu/29123/
title: Severe Sepsis: A Science of Uncertainty
creator: Dezfulian, C
creator: Auerbach, J
description: An evaluation of a recent study by Kaukonen KM, Bailey M, Suzuki S et al: Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
date: 2015-01-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29123/1/10.12688_f1000research.6814.1_20151120.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29123/7/licence.txt
identifier:   Dezfulian, C and Auerbach, J  (2015) Severe Sepsis: A Science of Uncertainty.  F1000Research, 4.   ISSN 2046-1402     
relation: 10.12688/f1000research.6814.1

relation: http://d-scholarship-dev.library.pitt.edu/29122/
title: Should we use lung protective ventilation for non-ARDS patients?
creator: Kaynar, AM
creator: Singh, M
description: An evaluation of a recent study by Serpa Neto A, Cardoso SO and Manetta JA et al: Association between Uses of Lung-Protective Ventilation with Lower Tidal Volume and Clinical Outcomes among Patients without Acute Respiratory Distress Syndrome a Meta-analysis.
date: 2015-01-01
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29122/1/10.12688_f1000research.6815.1_20151120.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29122/7/licence.txt
identifier:   Kaynar, AM and Singh, M  (2015) Should we use lung protective ventilation for non-ARDS patients?  F1000Research, 4.   ISSN 2046-1402     
relation: 10.12688/f1000research.6815.1

relation: http://d-scholarship-dev.library.pitt.edu/29269/
title: Sleep and REM sleep disturbance in the pathophysiology of PTSD: The role of extinction memory
creator: Pace-Schott, EF
creator: Germain, A
creator: Milad, MR
description: Post-traumatic stress disorder (PTSD) is accompanied by disturbed sleep and an impaired ability to learn and remember extinction of conditioned fear. Following a traumatic event, the full spectrum of PTSD symptoms typically requires several months to develop. During this time, sleep disturbances such as insomnia, nightmares, and fragmented rapid eye movement sleep predict later development of PTSD symptoms. Only a minority of individuals exposed to trauma go on to develop PTSD. We hypothesize that sleep disturbance resulting from an acute trauma, or predating the traumatic experience, may contribute to the etiology of PTSD. Because symptoms can worsen over time, we suggest that continued sleep disturbances can also maintain and exacerbate PTSD. Sleep disturbance may result in failure of extinction memory to persist and generalize, and we suggest that this constitutes one, non-exclusive mechanism by which poor sleep contributes to the development and perpetuation of PTSD. Also reviewed are neuroendocrine systems that show abnormalities in PTSD, and in which stress responses and sleep disturbance potentially produce synergistic effects that interfere with extinction learning and memory. Preliminary evidence that insomnia alone can disrupt sleep-dependent emotional processes including consolidation of extinction memory is also discussed. We suggest that optimizing sleep quality following trauma, and even strategically timing sleep to strengthen extinction memories therapeutically instantiated during exposure therapy, may allow sleep itself to be recruited in the treatment of PTSD and other trauma and stress-related disorders.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29269/1/art%253A10.1186%252Fs13587-015-0018-9.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29269/7/licence.txt
identifier:   Pace-Schott, EF and Germain, A and Milad, MR  (2015) Sleep and REM sleep disturbance in the pathophysiology of PTSD: The role of extinction memory.  Biology of Mood and Anxiety Disorders, 5 (1).       
relation: 10.1186/s13587-015-0018-9

relation: http://d-scholarship-dev.library.pitt.edu/25536/
title: Standing strong in the winds of change: An analysis of a document delivery service in South Korea
creator: Oh, JS
creator: Lee, JW
description: Purpose – This paper aims to review the evolution of a nation-wide Document Delivery Service in Korea over the past decade, focusing on how the service has been reconfigured to sustain and fortify its position as a central channel for accessing information in the era of abundant digital resources. Design/methodology/approach – The impacts of policy changes and technical improvements introduced incrementally over the years on the advance of the service are analyzed. The overall statistics over the period of 14 years are first presented to show the changing trends of the service, and the transaction log of the period of nine years is analyzed in detail to examine the impact of policy implementation and technical advancement on the quantity and quality of the service. Findings – The transaction log analysis has uncovered the two main themes or directions of changes that have contributed to its robustness. First, changes introduced to streamline the service process both on the request end (unmediated requests) and on the delivery end (electronic delivery) have brought a sizable improvement on the speed of the service. Second, efforts to incorporate various resource-sharing activities into a unified service framework have led to an enhanced efficiency of the service as well as an increase in volume. Originality/value – The empirical data demonstrating how managerial and technological changes have contributed to sustain the value of the service can be valuable benchmarking data for other services facing the same challenges.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25536/1/licence.txt
identifier:   Oh, JS and Lee, JW  (2015) Standing strong in the winds of change: An analysis of a document delivery service in South Korea.  Interlending and Document Supply, 43 (1).  47 - 52.  ISSN 0264-1615     
relation: 10.1108/ILDS-04-2014-0022

relation: http://d-scholarship-dev.library.pitt.edu/22056/
title: Understanding route choices for wheelchair navigation
creator: Kasemsuppakorn, P
creator: Karimi, HA
creator: Ding, D
creator: Ojeda, MA
description: Purpose: To validate a personalized routing technique with wheelchair users, understand their route choices and acquire their feedback on the necessity of wheelchair navigation and the importance of personalized routes. Method: A routing technique using a weighting method, called Absolute Restriction Method (ARM), was employed to compute personalized routes based on users' routing preferences. The evaluation involves five manual wheelchair users. The study protocol consists of three sessions: pre-activity, activity and post-activity sessions. The evaluation included a comparison between personalized routes and shortest feasible routes, in terms of route characteristics and users' ratings of important parameters. Results: Subjects travelled a 14.64% longer distance along the personalized routes than the shortest feasible routes. However, all personalized routes had better path quality (slope and surface condition) than the shortest feasible routes. Four out of five subjects rated the parameters they deemed most important higher for the personalized route than for the shortest feasible route. Conclusions: The study confirmed that the shortest route criterion is not always suitable for individuals with mobility impairments. Personalized routes that take into account individual characteristics, route preferences and environmental characteristics are a promising solution to lessen the difficulties that manual wheelchair users face when navigating unfamiliar environments.Implications for RehabilitationWheelchair users indicate the importance of personalized routes for individuals with mobility impairments.In regard to evaluation results, although subjects travelled 14.64% more distances in average along the personalized routes than the shortest feasible routes, they rated the personalized routes better path quality and less effort to travel.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22056/1/licence.txt
identifier:   Kasemsuppakorn, P and Karimi, HA and Ding, D and Ojeda, MA  (2015) Understanding route choices for wheelchair navigation.  Disability and Rehabilitation: Assistive Technology, 10 (3).  198 - 210.  ISSN 1748-3107     
relation: 10.3109/17483107.2014.898160

relation: http://d-scholarship-dev.library.pitt.edu/25928/
title: User-controllable personalization: A case study with SetFusion
creator: Parra, D
creator: Brusilovsky, P
description: In this research we investigated the role of user controllability on personalized systems by implementing and studying a novel interactive recommender interface, SetFusion. We examined whether allowing the user to control the process of fusing or integrating different algorithms (i.e., different sources of relevance) resulted in increased engagement and a better user experience. The essential contribution of this research stems from the results of a user study (N=40) of controllability in a scenario where users could fuse different recommendation approaches, with the possibility of inspecting and filtering the items recommended. First, we introduce an interactive Venn diagram visualization, which combined with sliders, can provide an efficient visual paradigm for information filtering. Second, we provide a three-fold evaluation of the user experience: objective metrics, subjective user perception, and behavioral measures. Through the analysis of these metrics, we confirmed results from recent studies, such as the effect of trusting propensity on accepting the recommendations and also unveiled the importance of features such as being a native speaker. Our results present several implications for the design and implementation of user-controllable personalized systems.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25928/1/IJHCS-SetFusion-after-rev-AcceptedCHanges.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25928/4/licence.txt
identifier:   Parra, D and Brusilovsky, P  (2015) User-controllable personalization: A case study with SetFusion.  International Journal of Human Computer Studies, 78.  43 - 67.  ISSN 1071-5819     
relation: 10.1016/j.ijhcs.2015.01.007

relation: http://d-scholarship-dev.library.pitt.edu/26143/
title: Using participatory design and visual narrative inquiry to investigate researchers’ data challenges and recommendations for library research data services
creator: Mattern, E
creator: Jeng, W
creator: He, D
creator: Lyon, L
creator: Brenner, A
description: Purpose – The purpose of this paper is to report on an information gathering study on users’ research data-related challenges and proposals for library research data services (RDS). This study probes how early career researchers visually conceptualize the research process in their disciplines, their self-reported research data challenges, and their recommendations for library RDS. Design/methodology/approach – Two focus group sessions were undertaken with a total of eight early career researchers. Adopting the visual narrative inquiry method, the participants were asked to sketch the general research process in their domain. The individuals’ illustrations of the research process were then used as the basis for reflecting on their data-related needs and potential RDS that would assist them during the research process. Findings – Participants presented a research process that was more personal and, in most cases, more imperfect than the research lifecycle models that academic libraries are increasingly using for RDS development and communication. The authors present their data-related challenges, which included data access barriers, low knowledge of best practices for research data management, the need for a deeper understanding of post-publication impact, and inconsistent awareness of existing library and institution RDS. The authors outline RDS recommendations that participants proposed, which included a web-based tools, customized training sessions, and “distilled” guides to research data best practices. Practical implications – The study flagged users’ gaps in understandings of existing library and institutional RDS, suggesting that there may be an opportunity to engage users in the design of communications plans for services. The findings from this user study will inform the development of RDS at the institution. Originality/value – This paper puts forth a methodological approach that academic libraries can adapt for understanding users’ needs and user-generated design solutions.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26143/1/MatternEtAl_FinalPrePrint.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26143/4/licence.txt
identifier:   Mattern, E and Jeng, W and He, D and Lyon, L and Brenner, A  (2015) Using participatory design and visual narrative inquiry to investigate researchers’ data challenges and recommendations for library research data services.  Program, 49 (4).  408 - 423.  ISSN 0033-0337     
relation: 10.1108/PROG-01-2015-0012

relation: http://d-scholarship-dev.library.pitt.edu/24081/
title: Variability in Tuberculosis Granuloma T Cell Responses Exists, but a Balance of Pro- and Anti-inflammatory Cytokines Is Associated with Sterilization
creator: Gideon, HP
creator: Phuah, JY
creator: Myers, AJ
creator: Bryson, BD
creator: Rodgers, MA
creator: Coleman, MT
creator: Maiello, P
creator: Rutledge, T
creator: Marino, S
creator: Fortune, SM
creator: Kirschner, DE
creator: Lin, PL
creator: Flynn, JAL
description: Lung granulomas are the pathologic hallmark of tuberculosis (TB). T cells are a major cellular component of TB lung granulomas and are known to play an important role in containment of Mycobacterium tuberculosis (Mtb) infection. We used cynomolgus macaques, a non-human primate model that recapitulates human TB with clinically active disease, latent infection or early infection, to understand functional characteristics and dynamics of T cells in individual granulomas. We sought to correlate T cell cytokine response and bacterial burden of each granuloma, as well as granuloma and systemic responses in individual animals. Our results support that each granuloma within an individual host is independent with respect to total cell numbers, proportion of T cells, pattern of cytokine response, and bacterial burden. The spectrum of these components overlaps greatly amongst animals with different clinical status, indicating that a diversity of granulomas exists within an individual host. On average only about 8% of T cells from granulomas respond with cytokine production after stimulation with Mtb specific antigens, and few “multi-functional” T cells were observed. However, granulomas were found to be “multi-functional” with respect to the combinations of functional T cells that were identified among lesions from individual animals. Although the responses generally overlapped, sterile granulomas had modestly higher frequencies of T cells making IL-17, TNF and any of T-1 (IFN-γ, IL-2, or TNF) and/or T-17 (IL-17) cytokines than non-sterile granulomas. An inverse correlation was observed between bacterial burden with TNF and T-1/T-17 responses in individual granulomas, and a combinatorial analysis of pair-wise cytokine responses indicated that granulomas with T cells producing both pro- and anti-inflammatory cytokines (e.g. IL-10 and IL-17) were associated with clearance of Mtb. Preliminary evaluation suggests that systemic responses in the blood do not accurately reflect local T cell responses within granulomas.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24081/1/journal.ppat.1004603.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24081/4/licence.txt
identifier:   Gideon, HP and Phuah, JY and Myers, AJ and Bryson, BD and Rodgers, MA and Coleman, MT and Maiello, P and Rutledge, T and Marino, S and Fortune, SM and Kirschner, DE and Lin, PL and Flynn, JAL  (2015) Variability in Tuberculosis Granuloma T Cell Responses Exists, but a Balance of Pro- and Anti-inflammatory Cytokines Is Associated with Sterilization.  PLoS Pathogens, 11 (1).  1 - 28.  ISSN 1553-7366     
relation: 10.1371/journal.ppat.1004603

relation: http://d-scholarship-dev.library.pitt.edu/29261/
title: Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study
creator: Nguyen, NLH
creator: Pilewski, JM
creator: Celedón, JC
creator: Mandalapu, S
creator: Blanchard, ML
creator: DeRicco, A
creator: Hartigan, E
creator: Alcorn, JF
creator: Kolls, JK
description: Background: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH) vitamin D of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. Methods: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus- specific IgE, vitamin D levels, FEV , urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. Results: Six months of vitamin D supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). Conclusions: 4000 IU vitamin D daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. 2 3 3 3 1 3 3
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29261/1/art%253A10.1186%252Fs40733-015-0003-5.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29261/7/licence.txt
identifier:   Nguyen, NLH and Pilewski, JM and Celedón, JC and Mandalapu, S and Blanchard, ML and DeRicco, A and Hartigan, E and Alcorn, JF and Kolls, JK  (2015) Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study.  Asthma Research and Practice, 1 (1).       
relation: 10.1186/s40733-015-0003-5

relation: http://d-scholarship-dev.library.pitt.edu/22097/
title: A comparative analysis of routes generated by Web Mapping APIs
creator: Socharoentum, M
creator: Karimi, HA
description: Web Mapping APIs (WMAs), such as Google Maps API, are widely used by researchers across different fields to develop geospatial Web applications. Among maps and map functionalities provided through WMAs, route and direction are prominent and commonly available. Given that each WMA uses a different map database and a different set of assumptions, the routes they generate, for the same pairs of origin and destination addresses, are different. Considering the current void in literature on WMAs and the routes they generate, in this paper, select common WMAs are compared and analyzed based on their routing techniques. The results of these comparisons will benefit researchers by helping them better understand the behavior of WMAs in producing routes, which in turn can be used for selecting suitable WMAs for research projects or developing applications (such as navigation and location-based services). The process in which routes are evaluated can also be used as a guideline to help researchers explore behavior of WMAs in generating routes.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22097/1/licence.txt
identifier:   Socharoentum, M and Karimi, HA  (2015) A comparative analysis of routes generated by Web Mapping APIs.  Cartography and Geographic Information Science, 42 (1).  33 - 43.  ISSN 1523-0406     
relation: 10.1080/15230406.2014.976656

relation: http://d-scholarship-dev.library.pitt.edu/22982/
title: The impact of analogies on creative concept generation: Lessons from an in vivo study in engineering design
creator: Chan, J
creator: Schunn, C
description: Research on innovation often highlights analogies from sources outside the current problem domain as a major source of novel concepts; however, the mechanisms underlying this relationship are not well understood. We analyzed the temporal interplay between far analogy use and creative concept generation in a professional design team's brainstorming conversations, investigating the hypothesis that far analogies lead directly to very novel concepts via large steps in conceptual spaces (jumps). Surprisingly, we found that concepts were more similar to their preceding concepts after far analogy use compared to baseline situations (i.e., without far analogy use). Yet far analogies increased the team's concept generation rate compared to baseline conditions. Overall, these results challenge the view that far analogies primarily lead to novel concepts via jumps in conceptual spaces and suggest alternative pathways from far analogies to novel concepts (e.g., iterative, deep exploration within a functional space).
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22982/1/licence.txt
identifier:   Chan, J and Schunn, C  (2015) The impact of analogies on creative concept generation: Lessons from an in vivo study in engineering design.  Cognitive Science, 39 (1).  126 - 155.  ISSN 0364-0213     
relation: 10.1111/cogs.12127

relation: http://d-scholarship-dev.library.pitt.edu/25529/
title: A new Bayesian network-based risk stratification model for prediction of short-term and long-term LVAD mortality
creator: Loghmanpour, NA
creator: Kanwar, MK
creator: Druzdzel, MJ
creator: Benza, RL
creator: Murali, S
creator: Antaki, JF
description: Existing risk assessment tools for patient selection for left ventricular assist devices (LVADs) such as the Destination Therapy Risk Score and HeartMate II Risk Score (HMRS) have limited predictive ability. This study aims to overcome the limitations of traditional statistical methods by performing the first application of Bayesian analysis to the comprehensive Interagency Registry for Mechanically Assisted Circulatory Support dataset and comparing it to HMRS. We retrospectively analyzed 8,050 continuous flow LVAD patients and 226 preimplant variables. We then derived Bayesian models for mortality at each of five time end-points postimplant (30 days, 90 days, 6 month, 1 year, and 2 years), achieving accuracies of 95%, 90%, 90%, 83%, and 78%, Kappa values of 0.43, 0.37, 0.37, 0.45, and 0.43, and area under the receiver operator characteristic (ROC) of 91%, 82%, 82%, 80%, and 81%, respectively. This was in comparison to the HMRS with an ROC of 57% and 60% at 90 days and 1 year, respectively. Preimplant interventions, such as dialysis, ECMO, and ventilators were major contributing risk markers. Bayesian models have the ability to reliably represent the complex causal relations of multiple variables on clinical outcomes. Their potential to develop a reliable risk stratification tool for use in clinical decision making on LVAD patients encourages further investigation.
date: 2015-01-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25529/1/licence.txt
identifier:   Loghmanpour, NA and Kanwar, MK and Druzdzel, MJ and Benza, RL and Murali, S and Antaki, JF  (2015) A new Bayesian network-based risk stratification model for prediction of short-term and long-term LVAD mortality.  ASAIO Journal, 61 (3).  313 - 323.  ISSN 1058-2916     
relation: 10.1097/MAT.0000000000000209

relation: http://d-scholarship-dev.library.pitt.edu/28573/
title: An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses
creator: Schreiber, CA
creator: Sakuma, T
creator: Izumiya, Y
creator: Holditch, SJ
creator: Hickey, RD
creator: Bressin, RK
creator: Basu, U
creator: Koide, K
creator: Asokan, A
creator: Ikeda, Y
description: Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors.
date: 2015-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28573/1/journal.ppat.1005082.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28573/3/licence.txt
identifier:   Schreiber, CA and Sakuma, T and Izumiya, Y and Holditch, SJ and Hickey, RD and Bressin, RK and Basu, U and Koide, K and Asokan, A and Ikeda, Y  (2015) An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses.  PLoS Pathogens, 11 (8).   ISSN 1553-7366     
relation: 10.1371/journal.ppat.1005082

relation: http://d-scholarship-dev.library.pitt.edu/28201/
title: Accessible Wayfinding Testbed: Infrastructure and Components
creator: Karimi, Hassan A
creator: Hashemi, Mahdi
description: Despite considerable recent interest in research related to wayfinding and navigation of pedestrians, the needs and preferences of people with disabilities (PWDs) are not yet fully addressed. Some of still unaddressed issues are related to understanding the different mobility challenges of PWDs, while others are related to the accessibility of routes and navigation systems/services. Emergence of advanced systems and services that can assist PWDs in wayfinding and navigation calls for the development of an accessible wayfinding platform facilitating the evaluation of accessibility of indoor and outdoor routes. In this paper, we propose and present an accessible wayfinding testbed which has three components: database, accessibility index, and visualization. The database component includes networks of sidewalks outdoors and building elements indoors with accessibility elements for PWDs. The accessibility index determines the level of accessibility of each element in a network as is perceived by PWDs. The visualization component visualizes the routes, accessible and others, in a simple form allowing PWDs, urban planners, and software developers, among others, to evaluate the accessibility of the travelling environment. The paper discusses the details of the testbed and a prototype accessible wayfinding testbed.
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28201/1/icst.tridentcom.2015.259709.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28201/4/licence.txt
identifier:   Karimi, Hassan A and Hashemi, Mahdi  (2015) Accessible Wayfinding Testbed: Infrastructure and Components.  EAI Endorsed Transactions on Cloud Systems, 1 (2).       
relation: http://eudl.eu/doi/10.4108/icst.tridentcom.2015.259709
relation: 10.4108/icst.tridentcom.2015.259709

relation: http://d-scholarship-dev.library.pitt.edu/25880/
title: Automatic Evaluation of Information Provider Reliablity and Expertise
creator: Pelechrinis, Konstantinos
creator: Zadorozhny, Vladimir
creator: Kounev, Velin
creator: Oleshchuk, Vladimir
creator: Anwar, Mohd
creator: Lin, Yi-Ling
description: Q&A social media have gained a lot of attention during the recent years. People rely on these sites to obtain information due to a number of advantages they offer as compared to conventional sources of knowledge (e.g., asynchronous and convenient access). However, for the same question one may find highly contradicting answers, causing an ambiguity with respect to the correct information. This can be attributed to the presence of unreliable and/or non-expert users. These two attributes (reliability and expertise) significantly affect the quality of the answer/information provided. We present a novel approach for estimating these user's characteristics relying on human cognitive traits. In brief, we propose each user to monitor the activity of his peers (on the basis of responses to questions asked by him) and observe their compliance with predefined cognitive models. These observations lead to local assessments that can be further fused to obtain a reliability and expertise consensus for every other user in the social network (SN). For the aggregation part we use subjective logic. To the best of our knowledge this is the first study of this kind in the context of Q&A SNs. Our proposed approach is highly distributed; each user can individually estimate the expertise and the reliability of his peers using his direct interactions with them and our framework. The online SN (OSN), which can be considered as a distributed database, performs continuous data aggregation for users expertise and reliability assesment in order to reach a consensus. In our evaluations, we first emulate a Q&A SN to examine various performance aspects of our algorithm (e.g., convergence time, responsiveness etc.). Our evaluations indicate that it can accurately assess the reliability and the expertise of a user with a small number of samples and can successfully react to the latter's behavior change, provided that the cognitive traits hold in practice. Furthermore, the use of the consensus operator for the aggregation of multiple opinions on a specific user, reduces the uncertainty with regards to the final assessment. However, as real data obtained from Yahoo! Answers imply, the pairwise interactions between specific users are limited. Hence, we consider the aggregate set of questions as posted from the system itself and we assess the expertise and realibility of users based on their response behavior. We observe, that users have different behaviors depending on the level at which we are observing them. In particular, while their activity is focused on a few general categories, yielding them reliable, their microscopic (within general category) activity is highly scattered.
publisher: Springer
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25880/1/main.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25880/4/licence.txt
identifier:   Pelechrinis, Konstantinos and Zadorozhny, Vladimir and Kounev, Velin and Oleshchuk, Vladimir and Anwar, Mohd and Lin, Yi-Ling  (2015) Automatic Evaluation of Information Provider Reliablity and Expertise.  World Wide Web Journal, 18 (1).       

relation: http://d-scholarship-dev.library.pitt.edu/29031/
title: Biologically-active exosomes in plasma of AML patients inhibit innate immunity and promote leukemia progression
creator: Boyiadzis, Michael
creator: Hong, Chang-Sook
creator: Whiteside, Theresa L
publisher: BMJ
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29031/1/art%253A10.1186%252F2051-1426-3-S2-P278.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29031/7/licence.txt
identifier:   Boyiadzis, Michael and Hong, Chang-Sook and Whiteside, Theresa L  (2015) Biologically-active exosomes in plasma of AML patients inhibit innate immunity and promote leukemia progression.  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P278 - P278.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-s2-p278
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29036/
title: Circulating exosomes carrying an immunosuppressive cargo may interfere with adoptive cell therapies in leukemia
creator: Boyiadzis, Michael
creator: Hong, Chang-Sook
creator: Whiteside, Theresa L
publisher: BMJ
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29036/1/art%253A10.1186%252F2051-1426-3-S2-P60.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29036/7/licence.txt
identifier:   Boyiadzis, Michael and Hong, Chang-Sook and Whiteside, Theresa L  (2015) Circulating exosomes carrying an immunosuppressive cargo may interfere with adoptive cell therapies in leukemia.  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P60 - P60.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-s2-p60
language: en

relation: http://d-scholarship-dev.library.pitt.edu/26177/
title: Clear goal, clear results: Content-Focused Coaching supports learning for everyone – including coaches.
creator: Matsumura, Lindsay Clare
creator: Bickel, DB
creator: Berstein-Danis, T
date: 2015
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26177/1/licence.txt
identifier:   Matsumura, Lindsay Clare and Bickel, DB and Berstein-Danis, T  (2015) Clear goal, clear results: Content-Focused Coaching supports learning for everyone – including coaches.  Journal of Staff Development, 36 (1).  34 - 39.  ISSN 0276-928X     
relation: http://learningforward.org/publications/jsd/jsd-blog/jsd/2015/02/03/jsd-february-2015-coaching#.VhabF_lViko

relation: http://d-scholarship-dev.library.pitt.edu/28982/
title: The Evolution of Scientific Productivity of Junior Scholars
creator: Tsai, Chun-Hua
creator: Lin, Yu-Ru
description: Publishing academic work has been recognized as a key indicator for measuring scholars' scientific productivity and having crucial impact on their future career. However, little has been known about how the majority of researchers progress in publishing papers across disciplines. In this work, using a collection consisting of over five millions academic publications across 15 disciplines, we study how the scientific productivity patterns of junior scholars change across different generations and different domains. Our study results help understand the evolution of the competitive ``publish or perish'' academic culture.
publisher: iSchools
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28982/1/402_ready.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28982/7/licence.txt
identifier:   Tsai, Chun-Hua and Lin, Yu-Ru  (2015) The Evolution of Scientific Productivity of Junior Scholars.  iConference 2015 Proceedings.       

relation: http://d-scholarship-dev.library.pitt.edu/29020/
title: Ex-Th17 Foxp3+ T cells - a novel subset of Foxp3+ T cells induced in cancer
creator: Downs-Canner, Stephanie
creator: Ravindranathan, Roshni
creator: Edwards, Robert P
creator: Kalinski, Pawel
creator: Odunsi, Kunle
creator: Bartlett, David L
creator: Obermajer, Natasa
publisher: BMJ
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29020/1/art%253A10.1186%252F2051-1426-3-S2-P273.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29020/7/licence.txt
identifier:   Downs-Canner, Stephanie and Ravindranathan, Roshni and Edwards, Robert P and Kalinski, Pawel and Odunsi, Kunle and Bartlett, David L and Obermajer, Natasa  (2015) Ex-Th17 Foxp3+ T cells - a novel subset of Foxp3+ T cells induced in cancer.  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P273 - P273.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-s2-p273
language: en

relation: http://d-scholarship-dev.library.pitt.edu/28944/
title: Fast and accurate representations of stochastic ion channel fluctuations
creator: Anderson, David F
creator: Ermentrout, Bard
creator: Friel, David D
creator: Galán, Roberto F
creator: Lindner, Benjamin
creator: Pu, Shusen
creator: Schmidt, Deena R
creator: Thomas, Peter J
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28944/1/art%253A10.1186%252F1471-2202-16-S1-P258.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28944/7/licence.txt
identifier:   Anderson, David F and Ermentrout, Bard and Friel, David D and Galán, Roberto F and Lindner, Benjamin and Pu, Shusen and Schmidt, Deena R and Thomas, Peter J  (2015) Fast and accurate representations of stochastic ion channel fluctuations.  BMC Neuroscience, 16 (Suppl ).  P258 - P258.  ISSN 1471-2202     
relation: 10.1186/1471-2202-16-S1-P258

relation: http://d-scholarship-dev.library.pitt.edu/25267/
title: Graduate Archival Education in the United States; A Personal Reflection About Its Past and Future
creator: Cox, Richard J
description: From one vantage, those who started their careers decades ago, graduate archival education has made tremendous leaps forward; from another perspective, those in the early years of their careers, education in this field may look spotty, disjointed, and confusing. As I near the end of my career (although old archivists don’t fade away, they get preserved), I have increasingly felt like an archival source in ongoing professional dialogue. In this essay, I briefly consider the evolution of graduate education since the 1970s, the emergence of a new archival professorial corps, the maturing of our field’s professional and scholarly research, and the present characteristics of the archival academy. In this, I reflect as a transitional member of the academy, one who moved from practice to professing, and speculate about what the new generation of archival faculty – younger, less experienced, better educated, and research-driven, face in the next four decades. Examining current trends leads me to speculate about what graduate archival education will look like in 2050, and what I have to say is not what I am wishing for but what will likely occur. By 2050 I will be part of archival memory. What passes for archival education will be digital stewardship, delivered mostly via distance education with on-campus programs fewer in number and those that exist focused on doctoral studies and research, and masters programs mostly technical in nature and spread more broadly across the academy with a much more diverse group of students in terms of academic backgrounds and demographic characteristics.
publisher: Yale University Library and New England Archivists
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25267/1/Graduate_Archival_Education_in_the_United_States.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25267/4/licence.txt
identifier:   Cox, Richard J  (2015) Graduate Archival Education in the United States; A Personal Reflection About Its Past and Future.  Journal of Contemporary Archival Studies, 2 (Articl).  1 - 9.      

relation: http://d-scholarship-dev.library.pitt.edu/28608/
title: MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques ( Macaca sylvanus)
creator: Julle-Danière, Églantine
creator: Micheletta, Jérôme
creator: Whitehouse, Jamie
creator: Joly, Marine
creator: Gass, Carolin
creator: Burrows, Anne M.
creator: Waller, Bridget M.
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28608/1/peerj-1248.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/28608/4/licence.txt
identifier:   Julle-Danière, Églantine and Micheletta, Jérôme and Whitehouse, Jamie and Joly, Marine and Gass, Carolin and Burrows, Anne M. and Waller, Bridget M.  (2015) MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques ( Macaca sylvanus).  PeerJ, 3.  e1248 - e1248.      
relation: 10.7717/peerj.1248

relation: http://d-scholarship-dev.library.pitt.edu/26176/
title: Media literacies as pivots for “opening up” the figured world of English Language Arts
creator: Matsumura, Lindsay Clare
creator: Gomez, Zywica
publisher: Massachusetts Institute of Technology Press
date: 2015
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26176/1/licence.txt
identifier:   Matsumura, Lindsay Clare and Gomez, Zywica  (2015) Media literacies as pivots for “opening up” the figured world of English Language Arts.  International Journal of Learning and Media.   ISSN 1943-6068    (In Press)  

relation: http://d-scholarship-dev.library.pitt.edu/29037/
title: Metabolic insufficiency underlies intratumoral cytotoxic T cell dysfunction
creator: Gupta, Tushar
creator: Scharping, Nicole E
creator: Moreci, Rebecca S
creator: Delgoffe, Greg M
publisher: BMJ
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29037/1/art%253A10.1186%252F2051-1426-3-S2-P399.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29037/7/licence.txt
identifier:   Gupta, Tushar and Scharping, Nicole E and Moreci, Rebecca S and Delgoffe, Greg M  (2015) Metabolic insufficiency underlies intratumoral cytotoxic T cell dysfunction.  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P399 - P399.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-s2-p399
language: en

relation: http://d-scholarship-dev.library.pitt.edu/29015/
title: PD-1 blockade upregulate TIM-3 expression as a compensatory regulation of immune check point receptors in HNSCC TIL
creator: Shayan, Gulidanna
creator: Ferris, Robert L
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29015/1/art%253A10.1186%252F2051-1426-3-S2-P196.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29015/7/licence.txt
identifier:   Shayan, Gulidanna and Ferris, Robert L  (2015) PD-1 blockade upregulate TIM-3 expression as a compensatory regulation of immune check point receptors in HNSCC TIL.  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P196 - P196.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-S2-P196

relation: http://d-scholarship-dev.library.pitt.edu/29013/
title: A Phase Ib study of neoadjuvant immune biomarker modulation with cetuximab and motolimod in head and neck cancer (HNC)
creator: Ferris, Robert L
creator: Kansy, Benjamin A
creator: Gibson, Sandra
creator: Srivastava, Raghvendra M
creator: Bryan, James
creator: Hershberg, Robert M
publisher: BMJ
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29013/1/art%253A10.1186%252F2051-1426-3-S2-P144.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/29013/7/licence.txt
identifier:   Ferris, Robert L and Kansy, Benjamin A and Gibson, Sandra and Srivastava, Raghvendra M and Bryan, James and Hershberg, Robert M  (2015) A Phase Ib study of neoadjuvant immune biomarker modulation with cetuximab and motolimod in head and neck cancer (HNC).  Journal for ImmunoTherapy of Cancer, 3 (Suppl ).  P144 - P144.  ISSN 2051-1426     
relation: 10.1186/2051-1426-3-s2-p144
language: en

relation: http://d-scholarship-dev.library.pitt.edu/27180/
title: Phox2b is not specifically expressed by hindbrain glucagon-like peptide-1 (GLP-1) neurons.
creator: Hayes, MR
creator: Rinaman, Linda
creator: Skibicka, KP
creator: Trapp, S
creator: Williams, DL
date: 2015
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/27180/1/licence.txt
identifier:   Hayes, MR and Rinaman, Linda and Skibicka, KP and Trapp, S and Williams, DL  (2015) Phox2b is not specifically expressed by hindbrain glucagon-like peptide-1 (GLP-1) neurons.        (Submitted)  

relation: http://d-scholarship-dev.library.pitt.edu/26758/
title: Piglia y el Unabomber: literatura y política en El camino de Ida
creator: Balderston, Daniel
description: This article is a discussion of Ricardo Piglia's use of the Unabomber case in his novel El camino de Ida (2013), with attention to both Ted Kaczynski's and Piglia's interest in Joseph Conrad's novel The Secret Agent. It appears in a special issue of La Biblioteca entitled "El arte de narrar: Variaciones sobre Ricardo Piglia."
publisher: Biblioteca Nacional de la Republica Argentina
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: es
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26758/1/Piglia.PDF
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26758/3/licence.txt
identifier:   Balderston, Daniel  (2015) Piglia y el Unabomber: literatura y política en El camino de Ida.  La Biblioteca, 15.  308 - 317.  ISSN 0329-1588     

relation: http://d-scholarship-dev.library.pitt.edu/25259/
title: The Political Codification of Islamic Law: A Closer Look at the Draft Shi’i Personal Status Code of Iraq
creator: Hamoudi, Haider Ala
description: There is a regrettable tendency to equate social conservatism with religious adherence. Nowhere does this occur more than in the Muslim world, where conservatives are closely associated with adherence to shari’a. The more unyielding the conservative, the “stricter” the supposed adherence to shari’a, or, alternatively, the more “literal” the version of shari’a adhered to. While almost any social conservative movement in the Muslim world or otherwise professes adherence to religious doctrine as being the core of its ideological commitment, and while there are important ways in which Muslim social conservatives insist on adherence to religious rules in their most traditional forms, it is a mistake of category to equate the two. Religious doctrine does not always motivate Muslim social conservatives, and the commitments of those social conservatives often derogate from the demands of doctrine. The divergence between the two becomes particularly obvious in the context of the drafting of Islamic legislation that is intended to reflect historic and traditional Islamic rules. A particularly important example of this lies in the subject of examination of this Article — the recently promulgated draft “Ja’fari Personal Status Code” in Iraq, designed to rewrite the rules of personal status (encompassing primarily family law, wills and inheritance) for Iraq’s Shi’i population. The goal was ostensibly to bring those rules into conformity with long established Shi’i juristic interpretations of Islam’s sacred texts, in a Sunni dominated state that had spent decades repressing Shi’i jurists and marginalizing the rules they promulgated. Given the motivations of the project (to comply with a longstanding Shi’i demand to change the law to conform more closely to juristic rules), and given that within Shi’ism, the juristic rules are pronounced by modern authorities who continue to retain extremely high levels of legitimacy, one would expect that faithful and close adherence to religious rules would follow in this context if no other. Yet no such faithful adherence is found, and in fact the divergence from doctrine is so stark that the jurists themselves ultimately denounced the draft. Using examples such as prostitution, child marriage, slavery and female genital mutilation, the Article demonstrates the manner in which the draft Code diverges in significant ways from historic Shi’i doctrine in order to defer to preferences and commitments of socially conservative traditionalists who would otherwise claim adherence to the doctrine. It also shows that this sort of deference is exercised not only by lawmakers who seek to curry favor with conservative constituents, but that even the jurists themselves often downplay or obfuscate their own rules when they are aware that such rules are unlikely to be received with very much enthusiasm by the devout who profess, but do not practice, absolute devotion to them. The Article concludes with the observation that the perduring notion that conservatives seek “strict”, “pure” or “literalist” shari’a, while liberals wish to “reform” it is not only false, but also dangerous. This broad presumptive equivalence between close adherence to shari’a and Muslim social conservatism privileges the ideological preferences of the social conservative over those of the liberal in a manner that renders it all the more difficult to engage in meaningful religious reform within the Islamic tradition.
publisher: University of Arizona James E. Rogers College of Law
date: 2015
type: Article
type: NonPeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25259/1/licence.txt
identifier:   Hamoudi, Haider Ala  (2015) The Political Codification of Islamic Law: A Closer Look at the Draft Shi’i Personal Status Code of Iraq.  Arizona Journal of International and Comparative Law, 32 (2).  *** - ***.  ISSN 0743-6963     

relation: http://d-scholarship-dev.library.pitt.edu/25627/
title: The Political Codification of Islamic Law: A Closer Look at the Ja'fari Personal Status Code of Iraq
creator: Hamoudi, Haider Ala
description: There is a regrettable tendency to equate social conservatism with religious adherence. Nowhere does this occur more than in the Muslim world, where conservatives are closely associated with adherence to shari’a. The more unyielding the conservative, the “stricter” the supposed adherence to shari’a, or, alternatively, the more “literal” the version of shari’a adhered to. While almost any social conservative movement in the Muslim world or otherwise professes adherence to religious doctrine as being the core of its ideological commitment, and while there are important ways in which Muslim social conservatives insist on adherence to religious rules in their most traditional forms, it is a mistake of category to equate the two. Religious doctrine does not always motivate Muslim social conservatives, and the commitments of those social conservatives often derogate from the demands of doctrine. The divergence between the two becomes particularly obvious in the context of the drafting of Islamic legislation that is intended to reflect historic and traditional Islamic rules. A particularly important example of this lies in the subject of examination of this Article — the recently promulgated draft “Ja’fari Personal Status Code” in Iraq, designed to rewrite the rules of personal status (encompassing primarily family law, wills and inheritance) for Iraq’s Shi’i population. The goal was ostensibly to bring those rules into conformity with long established Shi’i juristic interpretations of Islam’s sacred texts, in a Sunni dominated state that had spent decades repressing Shi’i jurists and marginalizing the rules they promulgated. Given the motivations of the project (to comply with a longstanding Shi’i demand to change the law to conform more closely to juristic rules), and given that within Shi’ism, the juristic rules are pronounced by modern authorities who continue to retain extremely high levels of legitimacy, one would expect that faithful and close adherence to religious rules would follow in this context if no other. Yet no such faithful adherence is found, and in fact the divergence from doctrine is so stark that the jurists themselves ultimately denounced the draft. Using examples such as prostitution, child marriage, slavery and female genital mutilation, the Article demonstrates the manner in which the draft Code diverges in significant ways from historic Shi’i doctrine in order to defer to preferences and commitments of socially conservative traditionalists who would otherwise claim adherence to the doctrine. It also shows that this sort of deference is exercised not only by lawmakers who seek to curry favor with conservative constituents, but that even the jurists themselves often downplay or obfuscate their own rules when they are aware that such rules are unlikely to be received with very much enthusiasm by the devout who profess, but do not practice, absolute devotion to them. The Article concludes with the observation that the perduring notion that conservatives seek “strict”, “pure” or “literalist” shari’a, while liberals wish to “reform” it is not only false, but also dangerous. This broad presumptive equivalence between close adherence to shari’a and Muslim social conservatism privileges the ideological preferences of the social conservative over those of the liberal in a manner that renders it all the more difficult to engage in meaningful religious reform within the Islamic tradition.
date: 2015
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25627/1/SSRN_Version.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25627/4/licence.txt
identifier:   Hamoudi, Haider Ala  (2015) The Political Codification of Islamic Law: A Closer Look at the Ja'fari Personal Status Code of Iraq.  Arizona Journal of International and Comparative Law, 32 (2).      (In Press)  
relation: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2603811

relation: http://d-scholarship-dev.library.pitt.edu/26294/
title: Por un comunismo literario
creator: Duchesne Winter, Juan R
description: Draws on Jean-Luc Nancy's essay on "literary Communism" in order to relate contemporary literary criticism to the critique of the communist failure in the twentieth century and the posing a of a non-immanent and non-transcendental, non-Utopian literary politics.
publisher: Universidad Iberoamericana
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: es
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26294/1/Por_un_comunismo_literario.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26294/4/licence.txt
identifier:   Duchesne Winter, Juan R  (2015) Por un comunismo literario.  Libro Mercado: Literatura y neoliberalismo.       

relation: http://d-scholarship-dev.library.pitt.edu/26605/
title: Professional and Scholarly Writing: Advice for Information Professionals and Academics
creator: Cox, Richard J
description: There has been an explosion of new research and writing about all aspects of the information disciplines. Nevertheless, both academics and practitioners often find it difficult to engage in successful writing strategies. Indeed, writing is hard work, and doing it in a way that leads to publication is an even harder task. Since reading is essential to good writing, the challenges of learning to write are obvious. In this essay, I am drawing on many years of experience in writing and publishing, as well as considerable reading of writers’ memoirs, advice books on writing, literary studies, and other perspectives on the experience of writing in order to offer a set of approaches that can be pursued over a lifetime of scholarship and practice. Writing is a craft or art to be learned, and learning demands paying attention to the audience, having clear objectives, being an avid reader, and possessing the ability to accept and learn from criticism. While information professionals and scholars incessantly write for each other, there are large segments of the public and other disciplines who they ignore. Fortunately, the tools and resources for improving one’s writing are both broad and deep; discipline and realistic strategies are all that are required to improve one’s writing and, ultimately, to achieve success in publishing.
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26605/1/1202-1_Richard_J._Cox.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/26605/4/licence.txt
identifier:   Cox, Richard J  (2015) Professional and Scholarly Writing: Advice for Information Professionals and Academics.  Journal of Information Theory and Practice, 3 (4).  6 - 16.      

relation: http://d-scholarship-dev.library.pitt.edu/23984/
title: Senderos que se bifurcan: dos manuscritos de un cuento de Borges
creator: Balderston, Daniel
description: This article concerns two manuscripts of the Borges story "El jardín de senderos que se bifurcan" (The Garden of Forking Paths), showing the ways in which the features of the manuscripts are related to the theme of the story of the pullulation of multiple possibilities.
publisher: Paris VIII University, Vincennes-Saint Denis
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: es
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/23984/5/lirico-1992-12-senderos-que-se-bifurcan-dos-manuscritos-de-un-cuento-de-borges.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/23984/11/licence.txt
identifier:   Balderston, Daniel  (2015) Senderos que se bifurcan: dos manuscritos de un cuento de Borges.  Cuadernos LIRICO, 12.   ISSN 1779-7519     
relation: http://lirico.revues.org/1992

relation: http://d-scholarship-dev.library.pitt.edu/30286/
title: Strike Out: A Pirates Pitcher at the Battle of Homestead
creator: Brodt, Zachary L
description: The 1892 Homestead Steel Strike is one of the most notorious events of the American Labor Movement. While the conflict mainly pitted striking steelworkers against Pinkerton Detective Agents hired by Henry Clay Frick, many townspeople also participated in the event. One surprising participant was Homestead native and Pittsburg Pirates pitcher Mark Baldwin. This article examines Baldwin's life and career to identify the influences and experiences that led him tothe grounds of Carnegie Steel's Homestead Works on that fateful day.
publisher: Senator John Heinz History Center
date: 2015
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/30286/7/Strike%20Out%20published.pdf
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/30286/2/Strike_Out_submitted_final.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/30286/13/licence.txt
identifier:   Brodt, Zachary L  (2015) Strike Out: A Pirates Pitcher at the Battle of Homestead.  Western Pennsylvania History, 98 (2).  50 - 61.  ISSN 1525-4755     

relation: http://d-scholarship-dev.library.pitt.edu/25410/
title: Understanding Route Choices for Wheelchair Navigation
creator: Kasemsuppakorn, Piyawan
creator: Karimi, Hassan A
creator: Ding, Dan
creator: OJEDA AGUILAR, ALEJANDRA MANOELA
date: 2015
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/25410/1/licence.txt
identifier:   Kasemsuppakorn, Piyawan and Karimi, Hassan A and Ding, Dan and OJEDA AGUILAR, ALEJANDRA MANOELA  (2015) Understanding Route Choices for Wheelchair Navigation.  Disability and Rehabilitation: Assistive Technology, 10 (3).  198 - 210.      

relation: http://d-scholarship-dev.library.pitt.edu/36220/
title: The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.
creator: Türedi, Sibel
creator: Hancı, Hatice
creator: Topal, Zehra
creator: Ünal, Deniz
creator: Mercantepe, Tolga
creator: Bozkurt, İlyas
creator: Kaya, Haydar
creator: Odacı, Ersan
description: The growing spread of mobile phone use is raising concerns about the effect on human health of the electromagnetic field (EMF) these devices emit. The purpose of this study was to investigate the effects on rat pup heart tissue of prenatal exposure to a 900 megahertz (MHz) EMF. For this purpose, pregnant rats were divided into experimental and control groups. Experimental group rats were exposed to a 900 MHz EMF (1 h/d) on days 13-21 of pregnancy. Measurements were performed with rats inside the exposure box in order to determine the distribution of EMF intensity. Our measurements showed that pregnant experimental group rats were exposed to a mean electrical field intensity of 13.77 V/m inside the box (0.50 W/m(2)). This study continued with male rat pups obtained from both groups. Pups were sacrificed on postnatal day 21, and the heart tissues were extracted. Malondialdehyde, superoxide dismutase and catalase values were significantly higher in the experimental group rats, while glutathione values were lower. Light microscopy revealed irregularities in heart muscle fibers and apoptotic changes in the experimental group. Electron microscopy revealed crista loss and swelling in the mitochondria, degeneration in myofibrils and structural impairments in Z bands. Our study results suggest that exposure to EMF in the prenatal period causes oxidative stress and histopathological changes in male rat pup heart tissue.
date: 2015
type: Article
type: NonPeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/36220/1/RSM_Meta_Revisions_12312018_FinalVersion.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/36220/10/licenseagreement_dscholarship.txt
identifier:   Türedi, Sibel and Hancı, Hatice and Topal, Zehra and Ünal, Deniz and Mercantepe, Tolga and Bozkurt, İlyas and Kaya, Haydar and Odacı, Ersan  (2015) The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.  Electromagn Biol Med, 34 (4).  390 - 397.      
relation: 10.3109/15368378.2014.952742
language: eng