Digital Commons Network^™

Modulate Obesity And Related Metabolic Complications For Yielding Improvements In Ibd Outcomes (Modify-Ibd): Consensus On Obesity And Cardiometabolic Comorbidities In Inflammatory Bowel Disease Using Systematic Reviews And The Rand/Ucla Appropriateness Method, Jalpa Devi, Sami Samaan, Priya Sehgal, Mouhand Mohamed, Matthew Vincent, Shannon Coombs, Michelle Doering, Edward L. Barnes, Amanda M. Johnson, Andres J. Yarur, Parakkal Deepak

Division of Gastroenterology and Hepatology Faculty Papers

INTRODUCTION: Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabolic complIcations For Yielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research And Development/University of California, Los …

Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda

Department of Pediatrics Faculty Papers

BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF).

METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O

CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.

Holistic Management Of Epilepsy In Adults With Intellectual Development Disorders, Elena Fonseca, Antonella Riva, Samuel López‐Maza, Malin Zaddach, Marie‐Claire Porter, Ingo Borggraefe, Lance Watkins, Andreas Schulze‐Bonhage, Rohit Shankar, Pasquale Striano, Lina Nashef

Peninsula Medical School

This seminar addresses the complexity of the management of epilepsy in adults with intellectual development disorders (IDD), advocating holistic and multidisciplinary care aligned with the learning objectives of the International League Against Epilepsy. Epilepsy is significantly more prevalent in people with IDD, presenting unique diagnostic, therapeutic, and psychosocial challenges. Accurate diagnosis is hampered by limitations in communication, necessitating reliance on caregivers' observations. In adults with IDD and epilepsy, utilization of diagnostic tools, e.g., video electroencephalograph (EEG) monitoring, is helpful but can be challenging. Management requires careful consideration of cognitive and behavioral comorbidities and the effects of antiseizure medications (ASMs) on …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

Repurposing Semaglutide As An Adjunctive Treatment For Cocaine Use Disorder: Protocol For A Randomised Controlled Trial, Luba Yammine, Francesco Versace, Charles E Green, Heather E Webber, Jin Ho Yoon, Absalon D Gutierrez, Samuel J Leonard, Michael F Weaver, Joy Schmitz

Faculty, Staff and Student Publications

Introduction: Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

Methods and analysis: This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will …

A Review Of Robotic Vnotes Surgery: Current Applications, Advantages, And Future Directions, Daniel Y Lovell, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Over the past 500 years, the convergence of three distinct paths - vaginal surgery, laparoscopy, and robotic technologies - has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES). The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy, myomectomy, sacrocolpopexy, adnexal interventions, and oncologic operations, applicable to a wide range of diagnoses and pathologies. This approach offers patients significant benefits, including superior cosmetic outcomes, less pain, lower infection rates, and faster recovery of baseline quality of life. Surgeons benefit from improved ergonomics, better visualization, the ability to use multiple instruments, and enhanced …

Association Of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study Of Atherosclerosis, Seamus P Whelton, Jie Yao, Clary Clish, Alexis C Wood, Kent D Taylor, Michael J Blaha, Matthew Budoff, Natalie Marrero, George Thanassoulis, Wendy S Post, Xiuqing Guo, Jerome I Rotter

Faculty, Staff and Students Publications

Background: Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors.

Methods: We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at …

Human Papillomavirus Vaccine Discourse And Sentiment On Reddit Before And After Covid-19: Mixed Methods Retrospective Cross-Sectional Study, Marcin Marciniak, Sean A Setzen, Deeya Bhattacharya, Jamie Masliah, Robin Powszok, Erich M Sturgis, Vanessa C Stubbs, Mihir K Bhayani

Faculty, Staff and Students Publications

Background: Human papillomavirus (HPV) is a sexually transmitted virus that causes various oropharyngeal and anogenital cancers. The HPV vaccine provides protection against several strains of HPV and is a key preventative tool against HPV-related cancers; however, vaccination rates remain suboptimal in the United States due to variable state mandates and misperceptions of vaccine efficacy and risks. As social media becomes an increasingly popular avenue for health discussions, platforms such as Reddit offer opportunities to understand public vaccine discourse, particularly among underrepresented groups. Furthermore, vaccine hesitancy and mistrust generally increased during the COVID-19 pandemic, potentially impacting HPV vaccination rates.

Objective: This …

Investigating Racial Differences In The Receipt Of Antenatal Interventions Prior To Periviable Delivery, Niurka Monteserin, Whitney Bender

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The Society for Maternal Fetal Medicine (SMFM) provides guidance on the use of antenatal corticosteroids, antibiotics, and cesarean delivery in the periviable period. Although racial differences exist in postnatal active management of periviable neonates have been described, less is known about racial differences in antenatal interventions preceding delivery.

OBJECTIVE: To evaluate differences in the receipt of antenatal interventions before periviable delivery by birthing parent race.

METHODS:  We conducted a population-based cohort study using the National Center for Health Statistics database including periviable deliveries (20w0d-25w6d) from 2016-2021. Individuals delivering a non-anomalous live singleton gestation in a hospital were included. Births …

Use Of Tyrx Antibacterial Envelope In Inflatable Penile Prosthesis Surgery: A Prospective Pilot Study., Jack T. Rifkin, Julia A. Baran, Brian H. Im, Tej J. Desai, Jordan Dehoratius, Oleksandr Kolesnikov, Paul Chung

Department of Neurology Faculty Papers

BACKGROUND: Infection remains a major concern in inflatable penile prosthesis (IPP) surgery. Medtronic's TYRX Absorbable Antibacterial Envelope is a polypropylene mesh pocket delivering minocycline and rifampin for 7 days and fully absorbing in 9 weeks. It is currently FDA-approved for use with cardiac pacemakers and neuromodulation devices. There is no indication for use in IPP surgeries, particularly for enveloping the scrotal pump during implantation.

AIM: This pilot study evaluates the feasibility, safety, and early patient-reported outcomes with the use of the absorbable antibacterial envelope during IPP surgery.

METHODS: Fifteen men who underwent primary or revision IPP placement by a single …

Pneumomlpred: Innovating Pneumonia Management With Guideline Adherence Review And Explainable Machine Learning-Based Mortality Prediction - A Single-Centre Retrospective Study, Kamel A. Samara, Hiba Jawdat Barqawi, Saryia Adra, Batool Aldaher, Drishti D. Kampani, Enad Haddad, Hebah Soudan, Islam Ibrahim Anwar, Mohamad Besher Adi, Omar Hamadi, Yumna Almour, Mohamed Nassef, Zaher Al Aghbari, Eman Abu-Gharbieh

Abington Jefferson Health Papers

Introduction: Community-acquired pneumonia (CAP) is one of the leading causes of death globally. Changing antibiotic resistance profiles, paucity of reliable CAP mortality prediction models, and ageing populations will increase its burden. This study aims to evaluate adherence to CAP management guidelines as well as develop an ML-based mortality prediction model.

Methods: This retrospective, chart review included all CAP cases between 2016 and 2021. Variables collected included patients' demographics, comorbidities, vitals, laboratory, imaging, and culture findings, as well as initial and targeted antibiotic regimens. Data was pre-processed and analysed in python-3. Adherence to the American thoracic society/infectious diseases society of America …

Phase Ii Trial Of Sodium Phenylbutyrate And Taurursodiol In Wolfram Syndrome, Fumihiko Urano, Bess A. Marshall, Stacy Hurst, Amy Robichaux-Viehoever, Saumel Ahmadi, Tamara Hershey, Gregory Van Stavern, Paulina Cruz Bravo, Jennifer Powers Carson, John Pesko, Kelly Fox, Nathalie Erpelding, Camille L Bedrosian

2020-Current year OA Pubs

PB&TURSO was associated with improved or stabilized pancreatic function, vision, and overall symptom burden in individuals with Wolfram syndrome, a rare and progressive degenerative disease.

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …

Quantification Of Sarm1 Nadase Activity In Human Peripheral Blood Mononuclear Cells, Lila F Dabill, Ivana R Shen, Jennifer M Brazill, Alicia Neiner, Yo Sasaki, Erica L Scheller

2020-Current year OA Pubs

SARM1 (sterile α and TIR motif-containing protein-1) is an NADase enzyme that serves as the central executioner of Wallerian axon degeneration. Given this, SARM1 is of high interest as a candidate therapeutic target, and SARM1 inhibitors are currently in clinical trials for treatment of neurodegeneration. Beyond neuroscience, emerging studies reveal that SARM1 may also drive aspects of bone fragility, liver pathology, adipose expansion, and insulin resistance in metabolic disease. However, we lack methods to quantify SARM1 activation in humans to better define patients at high risk of SARM1-mediated tissue damage. Unlike neurons, peripheral blood mononuclear cells (PBMCs) represent an easily …

Type-1 Ryanodine Receptor Plays An Important Role In Cardiac Hypertrophy And Heart Failure By Increasing Type-2 Ryanodine Receptor-Mediated Calcium Release, Yong-Xiao Wang, Ed Wilson Santos, Sarahann Mistretta, Yuexing Yuan, Harold A. Singer, Shey-Shing Sheu, Yun-Min Zheng

Center for Translational Medicine Faculty Papers

Type-1 ryanodine receptor (RyR1) is essential for skeletal muscle contraction. This Ca²⁺ release channel is expressed in cardiac myocytes; however, its function remains elusive. Cardiac-specific RyR1 overexpression (OE) mice were generated under the cardiac-specific Myh6 promoter. Cardiac hypertrophy (CH), cardiac functions, and mechanistic changes in RyR1 OE and control (wildtype, WT) mice were assessed using hematoxylin and eosin staining, echocardiography, electrocardiogram, quantitative RT-PCR, Western blotting, [³H]-ryanodine binding assay, confocal microscope, ROS dye Amplex Red and 2′,7′-dichlorofluorescein diacetate. RyR1 OE mice had increased whole heart, left ventricular weight, and left ventricular wall thickness, but decreased cardiac output and …

Incorporating The Use Of Puppets And Puppetry-Based Approaches In Nutrition: A Scoping Review Of Interventions, Basil H. Aboul-Enein, Nada Benajiba, Majd Jan, Sarah Ali Alasmari, Patricia J. Kelly, Stephen F. Gambescia, Elizabeth Dodge

College of Nursing Faculty Papers & Presentations

Puppetry-based activities could serve as a low cost and manageable intervention in improving health-related outcomes. This review aims to identify the research to date and gaps in practice of the role and application of puppetry interventions in nutrition education. A scoping review was conducted using the PICOS framework and PRISMA-ScR guidelines, identifying studies across eight databases between January, 1980 and July, 2025.Twenty-five studies were identified, with the majority (n = 19) aimed at pre-school and school-aged children. Fifteen studies used quasi-experimental, pre-post designs. The use of hand and finger puppets was common, as well as videos and puppet theatre. …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R. Rao, Barbara C. Jobst, Jerzy P. Szaflarski, John D. Rolston, Lesley C. Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C. Dugan, David E. Burdette, Angela Y. Peters, Atif Sheikh, Kevin F. Haas, Dileep R. Nair, Lilit Mnatsakanyan, Imran H. Quraishi, Meriem K. Bensalem-Owen, Michael J. Doherty, Babak Razavi, Tiffany L. Fisher, Christopher T. Skidmore, Pradeep N. Modur, Tawnya M. Constantino, Vicenta Salanova, Andrew J. Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W. Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E. Maciver, Sanjay E. Patra, Edward F. Chang, Jon T. Willie, Ryder Gwinn, Travis Stoub, John M. Stern, Tami Crabtree, Cairn G. Seale, Sharon C. Mcfadden, Jacob F. Norman, Lise Johnson, Martha J. Morrell

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R Rao, Barbara C Jobst, Jerzy P Szaflarski, John D Rolston, Lesley C Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C Dugan, David E Burdette, Angela Y Peters, Atif Sheikh, Kevin F Haas, Dileep R Nair, Lilit Mnatsakanyan, Imran H Quraishi, Meriem K Bensalem-Owen, Rns System Pas Study, Michael J Doherty, Babak Razavi, Tiffany L Fisher, Christopher Skidmore, Pradeep N Modur, Tawnya M Constantino, Vicenta Salanova, Andrew J Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E Maciver, Sanjay E Patra, Edward F Chang, Jon T Willie, Ryder Gwinn, Travis Stoub, John M Stern, Tami Crabtree, Cairn G Seale, Sharon C Mcfadden, Jacob F Norman, Lise Johnson, Martha J Morrell

Faculty, Staff and Student Publications

Background and objectives: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

Methods: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Social Prescribing For Refugee Populations: A Rapid Realist Review Of International Evidence, Victoria Touzel, Doreen Reifegerste, Luisa Bartz, Anna-Lena Esser, Kerryn Husk

Peninsula Medical School

BackgroundSocial prescribing offers potential for addressing social determinants of health and supporting health equity among disadvantaged groups. However, evidence for refugee populations remains limited, despite this group facing profound social and systemic barriers. This rapid realist review synthesizes social prescribing and comparable social-capital based intervention evidence to address this gap.MethodsWe conducted a RAMESES-compliant rapid realist review supported by an expert advisory board. Searches across six databases (2014–2024) were supplemented by grey literature and citation chasing strategies. Eligible studies included refugee, asylum-seekers and forcibly displaced populations engaged in either formal social prescribing or comparably operationalized social-capital interventions. Synthesis developed Context-Mechanism-Outcome configurations …

Gaboxadol Increases Resting Theta And Alpha Power Without Affecting Evoked Responses In Fragile X Syndrome In A Home-Based Setting., Lisa A. De Stefano, Hyeonseok Kim, Craig A. Erickson, Lauren M. Schmitt, Kelli C. Dominick, Ernest V. Pedapati, Richard Huckle, Robert Wilson, Walker S. Mckinney Ph.D., Debra L. Reisinger, Meredith N. Nelson, Ashley E. Dapore, Paul S. Horn, Makoto Miyakoshi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fragile X syndrome (FXS) lacks FDA-approved treatments despite various small molecules contributing to phenotypic rescue in the FMR1 knockout (KO) mouse model. Translation from the mouse model has been hampered by phenotypic heterogeneity that contributes to participation barriers among participants who are most affected and may be unable to regularly visit the research laboratory. The current study utilized a crossover design to test the acute neural and behavioral effects of a single 10 mg dose of gaboxadol and the reliability of electroencephalography (EEG) and behavioral data collected in participant homes compared to the clinic.

METHODS: Ten adult males with …

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

Nudging Implementation Of Low Tidal Volume Ventilation: A Stepped Wedge, Cluster Randomized Trial, Meeta Prasad Kerlin, Michael O. Harhay, Fan Li, Dylan S. Small, Yingying Lu, Wei Wang, Barry D. Fuchs, Mark E. Mikkelsen, Teresa Tran, Aerielle Belk, Jasmine A. Silvestri, Tamar Klaiman, Stefania Scott, Elizabeth Levy, Michael W. Sjoding, Rachel Kohn, Karsten J. Roberts, Rinad S. Beidas, Scott D. Halpern

College of Health Professions Faculty Papers

BACKGROUND: "Nudges" embedded in the electronic health record (EHR) facilitate desired decisions while preserving autonomy and may provide a scalable strategy to overcome the common implementation barrier of lack of knowledge about a best practice. We sought to test whether EHR-based nudges targeting two intensive care unit (ICU) clinician groups would safely increase evidence-based use of low tidal volume ventilation.

METHODS: We performed a stepped-wedge, cluster randomized, hybrid type 3 effectiveness-implementation trial in 12 ICUs from February 2021 to May 2023 to test three nudges targeting clinicians responsible for order entry and respiratory therapists responsible for operationalizing orders and documentation. …

Systemic Α₂-Agonist Use And Lower Hazard Of Glaucoma Compared With Β-Blockers: A Cohort Study, Ibrahim Abboud, Amin Z. Khudari, Abdelaziz Abdelaal, Amr Almobayed, Subhi J. Al'aref, Jonathan S. Myers, Richard K. Lee, Abdelrahman M. Elhusseiny

Wills Eye Hospital Papers

OBJECTIVE: Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

METHODS AND ANALYSIS: We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) …

Short-Term Bayesian Influenza Forecasting In A Hospital Environment Using A Linear Kalman Filter., Shankar Kaleeswaran Mani, Grzegorz A Rempala, Eben Kenah, Fernanda L Schumacher

Ambulatory and Primary Care Articles

Accurately forecasting the weekly number of influenza (flu) lab tests and positive cases is important for hospitals as they work to plan staffing, manage supplies, and provide timely patient care. In this paper, we describe a practical use of a Bayesian Kalman filter to forecast weekly flu tests and positives in a hospital setting. Using data from a large hospital system in Ohio, we show that this approach, which blends real-time hospital information with historical patterns, offers a dependable way to anticipate flu-related patient volume as far as four weeks ahead.

Cd8+ T Cell Differentiation Into Nk-Like Effector Cells Drives Transplant Rejection, Dawei Zou, Stephanie G Yi, Yulin Dai, Luan Truong, Lillian W Gaber, Richard J Knight, Xiang Xiao, Rafik M Ghobrial, Xian C Li, Zhongming Zhao, Wenhao Chen, A Osama Gaber

Faculty, Staff and Student Publications

T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8+ T cell subset exhibiting killer cell lectin-like receptor (KLR)+ NK-like features. Mechanistic studies in mice showed that the KLR+ subset emerged de novo post-transplantation and dominated the CD8+ T cell infiltrate in rejecting allografts. These NK-like CD8+ T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the …

Genealogy-Based Trait Association With Locater Boosts Power At Loci With Allelic Heterogeneity, Xinxin Wang, Ryan Christ, Erica Young, Chul Joo Kang, Indraniel Das, Edward A Belter, Markku Laakso, Louis J M Aslett, David Steinsaltz, Nathan O Stitziel, Ira M Hall

2020-Current year OA Pubs

A key methodological challenge for genome-wide association studies is how to leverage haplotype diversity and allelic heterogeneity to improve trait association power, especially in noncoding regions where it is difficult to predict variant impacts and define functional units for variant aggregation. Genealogy-based association methods have the potential to bridge this gap by testing combinations of common and rare haplotypes based purely on their ancestral relationships. In parallel work, we have developed an efficient local ancestry inference engine and a novel statistical method (LOCATER) for combining signals present on different branches of a locus-specific haplotype tree. Here, we develop a genome-wide …

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

Faculty, Staff and Student Publications

Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Metabolic Dysfunction And Metabolic Management In Episodic Migraine, Delora E. Denney, Michael J. Marmura

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: Evidence suggests a significant link between migraine and metabolic syndrome,, especially in those with chronic or refractory migraine. Weight loss and exercise may effectively prevent migraine. Here, we review the evidence behind exercise and weight loss as migraine treatments.

RECENT FINDINGS: While metabolic syndrome and pain have long had a known association, only recently have strong studies demonstrated a higher risk of developing metabolic syndrome in people with migraine. Additionally, other sequelae of metabolic syndrome, obesity, hypertension, hypercoagulability, and diabetes also interplay with migraine. New medications like GLP-1 agonists may be a potential treatment for migraine as …

Experiences Of Discrimination, Paternal Support, And Hypertensive Disorders Of Pregnancy (Hdp) In The Miehr Study, Houston, Texas, Tahereh Alinia, Elaine Symanski, Juan Manuel Alvarez, Kristina Walker Whitworth

Faculty, Staff and Students Publications

Background: Discrimination is a psychosocial stressor that, through activation of stress-response pathways, may influence risk of adverse perinatal health outcomes. However, few studies have evaluated the association between discrimination and hypertensive disorders of pregnancy (HDP), and none have explored effect modification by race or paternal support, which may buffer the adverse effects of discrimination.

Methods: We included 1,847 non-Hispanic Black and White participants from the Maternal and Infant Environmental Health Riskscape (MIEHR) study. Krieger's validated Experiences of Discrimination (EOD) scale was used to assess occurrence (yes/no) and frequency (once, 2-3, ≥ 4 times) of discrimination in nine situations. We created …

Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock, Kelly E Sanders, Marissa D Pokharel, Baron K Osborn, Yao-Wei Wang, Charles E Wade, Lucy Z Kornblith, Mitchell J Cohen, Jessica C Cardenas

Faculty, Staff and Student Publications

Background: Hemorrhagic shock (HS) following traumatic injury is hallmarked by innate immune activation, hypercoagulability, and thromboinflammatory complications. To date, the direct link between HS, injury severity, and endothelial cell (EC) contributions to thromboinflammation remains poorly understood. The goals of this study were to determine the impact of injury severity and HS on endothelial-mediated thromboinflammation and examine whether these changes increase the propensity for thrombosis.

Methods: Plasma from 89 male trauma patients, stratified by HS and injury severity, and 10 healthy subjects were assessed for inflammatory mediators by BioPlex. Human lung microvascular endothelial cells were exposed to patient plasma for 4 …