Digital Commons Network^™

Fitness For All: Education For Gym Staff Supporting People With Disabilites, Bianca Loor, Mary Jan Greer, Alison Skean

Spring 2026 OTD Capstone Symposium

This capstone project, “Fitness for All: Education for Gym Staff Supporting People with Disabilities,” focuses on improving accessibility and inclusion within community fitness settings through staff education. Individuals with disabilities often encounter barriers in gyms due to limited staff training, lack of confidence, and insufficient knowledge of adaptive fitness practices.

To address this gap, a comprehensive, evidence-based training program was developed and implemented for gym staff at Crunch Fitness Orange Park. The program incorporated occupational therapy frameworks, including the Person-Environment-Occupation (PEO) model and the Occupational Therapy Practice Framework (OTPF-4), to promote inclusive and client-centered fitness practices.

Using a mixed-methods approach, …

Perceived Inadequate Neighborhood Food Shopping And Cardiovascular Disease Risk: The Multi-Ethnic Study Of Atherosclerosis, Amier Haidar, Ghadi Ghanem, Rishi Rikhi, Karol E Watson, Shreela V Sharma, Michael D Shapiro

Faculty, Staff and Student Publications

Background: Individuals with access to healthy food have healthier diets, improved cardiometabolic risk profiles, and decreased cardiovascular disease (CVD). However, previous studies have focused on the neighborhood food environment as distance to and density of food retailers. Our study examines the association between an individual's perceived adequacy of neighborhood food shopping and incident CVD.

Methods: We analyzed data from 6814 participants in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals aged 45 to 84 who were enrolled in the study between 2000 and 2002 and followed longitudinally. Cox proportional hazards models estimated hazard ratios (HRs) for …

Out-Of-Pocket Costs And Antihypertensive Medication Use Among Veterans: A Natural Experiment, Alexander R. Zheutlin, Alexander Chaitoff, Daniel Addo, Joshua A. Jacobs, Catherine G. Derington, Eric L. Stulberg, Peter A. Glynn, Bernardo Modenesi, Jordana B. Cohen, Adam P. Bress

Department of Neurology Faculty Papers

BACKGROUND: Blood pressure (BP) control remains suboptimal in the United States despite available low-cost antihypertensive medications. Even small out-of-pocket medication costs may contribute to adherence. We determined whether $0 versus >$0 out-of-pocket costs for antihypertensive medications is associated with differences in adherence, discontinuation, BP control, and cardiovascular outcomes.

METHODS: We included veterans with newly diagnosed hypertension who initiated antihypertensive medication in the Veterans Health Administration from 2004 to 2022. A fuzzy regression discontinuity design with 2-stage residual inclusion leveraged differences in medication copay policy at a 50% service-connected disability threshold (≥50% service-connected disability: $0 out-of-pocket cost versus < 50%: $8 monthly cost). Outcomes included 1-year medication nonadherence (proportion of days covered < 80%), 1-year medication discontinuation (no medication in the final 90 days of the study year), 1-year BP control (systolic BP/diastolic BP < 140/90 mm Hg and < 130/80 mm Hg) and cardiovascular disease events (myocardial infarction, coronary revascularization, peripheral artery disease, or stroke).

RESULTS: Among 417 …

Designing Next-Generation Cardiometabolic Outcome Trials For Obesity Medicines, Elke Platz, Alexander Peikert, Biykem Bozkurt, Bart Van Der Schueren, Javed Butler, Ildiko Lingvay, Darren K Mcguire, Faiez Zannad, Naveed Sattar

Faculty, Staff and Students Publications

The prevalence of obesity has reached pandemic proportions and is having enormous public health effects. Obesity increases the risk of type 2 diabetes, hypertension, chronic kidney disease, and cardiovascular (CV) disease including coronary artery disease, heart failure, atrial fibrillation, and stroke. Although initial randomized clinical trials of weight-loss strategies through diet and exercise or early medical therapies did not lead to improved CV outcomes, more recent trials using glucagon-like peptide-1 (GLP-1) receptor agonists in individuals with obesity have demonstrated CV benefits. At present, there are multiple cardiovascular outcome trials (CVOTs) of novel GLP-1 receptor agonists and investigational products targeting multiple …

Natural History Of 15 Patients With Autosomal Dominant Wfs1 Pathogenic Variants Associated With Sensorineural Hearing Loss And Optic Atrophy, Jessica P Roberts, Abby F Tang, Daniela Hernandez, Brianna Carman, Liam Oiknine, Cris Brown, Stacy Hurst, Yunshuo Tang, Fumihiko Urano

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant pathogenic variants in WFS1 cause a spectrum of disorders with phenotypic manifestations including low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, non-syndromic diabetes mellitus, and early-onset cataracts. These conditions are generally milder than autosomal recessive Wolfram syndrome, except for Hattersley-Urano syndrome. Despite growing recognition of these disorders, data on clinical progression and long-term outcomes remain limited. This study aims to expand knowledge on disease severity and progression in autosomal dominant WFS1-related disorders. APPROACH: Clinical data were obtained from the Washington University International Registry and Clinical Study for Wolfram Syndrome and …

An Emerging Approach To Ibd Treatment: Personalized Nutrition Through Gut Microbiome Optimization., Kafayat Yusuf, Thomas M. Attard, Mazin Al-Kasspooles, Shahid Umar

Manuscripts, Articles, Book Chapters and Other Papers

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing and remitting disease activity. Despite decades of research, a definitive cure for IBD remains elusive, as cycles of remission and flare-ups mark the disease course and often relies on long-term pharmacologic and supportive strategies. Increasing evidence indicates that diet and nutrition play an important role in modulating the outcomes of IBD. Although a wide range of dietary interventions has been explored, no universally effective approach has been established. Investigations have also proven that different dietary interventions can significantly affect clinical outcomes by altering gut …

Inflammation- And Resolution-Programmed Myeloid Circuits Govern Therapeutic Resistance In Epithelial And Mesenchymal Triple-Negative Breast Cancer, Liqun Yu, Charlotte Rivas, Fengshuo Liu, Yichao Shen, Ling Wu, Zhan Xu, Yunfeng Ding, Xiaoxin Hao, Weijie Zhang, Hilda L Chan, Jun Liu, Bo Wei, Yang Gao, Luis Becerra-Dominguez, Yi-Hsuan Wu, Siyue Wang, Tobie D Lee, Xuan Li, Xiang Chen, David G Edwards, Xiang H-F Zhang

Faculty, Staff and Students Publications

Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes - proinflammatory and proresolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas proresolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemoimmunotherapy, mesenchymal-like tumors expanded proresolution macrophages through phagocytosis/efferocytosis, ω-3 fatty acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory …

Beyond The Evidence: The Cervical Collar As Cultural Artefact, Tim Nutbeam

Peninsula Medical School

Background: Cervical collar application remains prevalent in trauma care despite the absence of evidence of neurological benefit from spinal immobilisation. Clinical behaviour in this area has proven resistant to change, and the persistence of the collar requires explanation beyond the evidential debate alone. The fear of cervical injury has origins that predate clinical practice. Neurobiological preparedness theory suggests that threat associations linked to survival-relevant stimuli are more rapidly acquired and more durably maintained than other learned fears; the cervical region is a plausible candidate for this form of prepared response. This disposition has been reinforced by centuries of cultural practice: …

Enhanced Dietary Monitoring Using Fecal Genomics For Childhood Malnutrition Interventions, Ammara Aqeel, Najeeha T Iqbal, Sanam Iram Soomro, Sheraz Ahmed, Teresa K Mcdonald, Olivia Osborne, Sharon Jiang, Nolan Ives, Kazi Ahsan, Fayaz Umrani, Michael J Barratt, Jeffrey I Gordon, Syed Asad Ali, Lawrence A David

2020-Current year OA Pubs

Ready-to-use therapeutic and supplementary foods (RUTF/RUSF) are a primary treatment for childhood malnutrition in Community Management of Acute Malnutrition (CMAM) programs. However, measuring intervention compliance is labor intensive and unreliable. We applied FoodSeq, a fecal genomic dietary assessment biomarker, in malnourished infants (3-15 months) from Matiari, Pakistan. FoodSeq identified a significant increase in the abundance of DNA from chickpea, a primary RUSF ingredient, during RUSF administration and captured region-specific complementary feeding practices, including age-inappropriate feeding practices such as wide-spread tea consumption. Our findings highlight the potential of dietary genomics as an empirical and scalable tool for compliance monitoring and dietary …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

International Consensus On The Evaluation And Management Of Hypothalamic Hamartomas: Results From A Modified Delphi Survey, Nathan T Cohen, Xiaotong Li, Madison M Berl, Chima O Oluigbo, Hiroshi Shirozu, Samuel F Berkovic, Margaret Zacharin, Wirginia Maixner, Andreas Schulze-Bonhage, Kerstin Klotz, Nicola Specchio, Sarah Ferrand-Sorbets, Christine Bulteau, Alexis A Arzimanoglou, Jean Regis, J Helen Cross, Martin M Tisdall, Hanna Richardson, Arthur Cukiert, Cristine Cukiert, Julia Jacobs, Elizabeth J Donner, Phillip L Pearl, John F Kerrigan, Angus A Wilfong, Kevin C J Yuen, Dennis J Dlugos, Daniel Curry, Irfan Ali, John Ragheb, Lisa Soeby, Erica Webster, William D Gaillard

Faculty, Staff and Students Publications

Background and objectives: Hypothalamic hamartomas (HH) are rare brain lesions associated with epilepsy and numerous comorbidities. Worldwide treatment is varied. There is a paucity of high-quality evidence to guide treatment. This study aimed to establish expert consensus on the evaluation and management of HH.

Methods: A modified Delphi survey was designed by the Medical Advisory Board of Hope for Hypothalamic Hamartomas and was conducted among 17 International League Against Epilepsy level II epilepsy surgery centers. The survey included 257 questions in round 1 and 81 refined questions in round 2, covering domains of diagnosis, imaging, medical and surgical treatment, neuropsychological …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

A Machine-Learning-Based Tool For Stroke Risk Prediction In Blunt Cerebrovascular Injury: Development And Preliminary Evaluation, Victoria Wagner, Joshua D Preston, Alejandro De Leon Castro, William F Mueller, Jonathan Nguyen, Manuel Garcia-Toca, Elizabeth R Benjamin, S Rob Todd, Jason D Sciarretta

Faculty, Staff and Student Publications

Purpose: Stroke risk correlates with the Biffl grading system in blunt cerebrovascular injury (BCVI). Although anti-thrombotic therapy is the mainstay of stroke prevention, no point-of-care clinical decision-support tool exists to guide timing for therapy. We sought to develop an interactive online calculator that incorporates patient-specific demographic and injury characteristics to estimate stroke risk and risk reduction with anti-thrombotic (AT) administration.

Methods: Data from BCVI patients (n = 1,197) at a Level I Trauma Center were retrospectively collected. Six machine learning methods were employed to predict stroke risk with and without AT therapy. Class imbalance was addressed using downsampling and/or class …

Constitutive Ampk Activation Prevents Hepatocellular Carcinoma Development Through Inhibition Of Hnf4Α Activity, Zhen Sun, Bernard Linares, Cassidy Urdiales, Fiyad Alsarmi, Boyuan Sang, Nagireddy Putluri, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality and is largely driven by metabolic disorders such as obesity and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a master regulator of metabolism, and its activation has been proposed as a therapeutic strategy for treating metabolic disorders. However, although AMPK activity is down-regulated in HCC, the precise role of AMPK in HCC development has not been clearly delineated. Here, we investigated the ability of constitutive AMPK activation to prevent HCC development using a constitutively active AMPK transgenic mouse model and a pharmacological AMPK activator. We observed that AMPK …

Reirradiation Treatment Effects In The Clinic (Retec) Proposal - Proof Of Concept Based On Spinal Cord Dose Tolerance For Reirradiation With Stereotactic Body Radiotherapy, Jimm Grimm, Anand Mahadevan, Olusola Obayomi-Davies, Scott G. Soltys, Arjun Sahgal, Kristin J. Redmond, Michael T. Milano, Wolfgang A. Tomé, Kenneth Brooks, Scott Dodd, John Austin Vargo, Gopal Subedi, Jinyu Xue, Bisher Ebid, Felix Ehret, Byung-Han Andrew Rhieu, Christoph Fürweger, Rachel Grimm, Alexander Muacevic, Vitali Moiseenko, Shalom Kalnicki, Mark Mclaughlin, Lawrence R. Kleinberg, John R. Adler, Iris C. Gibbs

College of Health Professions Faculty Papers

BACKGROUND: Since the inception of spinal radiosurgery decades ago, the factors influencing spinal cord recovery have remained unclear. Elucidating these factors would aid in reirradiation planning and delivery. We describe modeling reirradiation normal tissue complication probabilities (NTCP) from compiled published data, akin to the collaborative Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) projects.

PURPOSE: Simple dose-time recovery factors for the spinal cord serve as a basis to propose the Reirradiation Treatment Effects in the Clinic (ReTEC) project. ReTEC aims to define human organ recovery factors …

Utility Of Right Ventricular Mass Ratios In Recipients With Pulmonary Hypertension: A United Network For Organ-Sharing Database Analysis, Matthew P. Weber, Danial Ahmad, Howard J. Eisen, Eugene Storozynsky, René J. Alvarez, J. Eduardo Rame, Keshava Rajagopal, John W. Entwistle, Charles Hoopes, Vakhtang Tchantchaleishvili

Division of Cardiology Faculty Papers

PURPOSE: There is a lack of data reviewing the role of predicted cardiac mass ratio (PCMR) in transplant recipients with pulmonary hypertension (PH). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of PCMR not yet studied separately for this purpose. We aimed to review the relationship of PCMR and RVMR with PH in terms of post-transplant overall survival.

METHODS: The United Network for Organ-Sharing (UNOS) database was queried for primary heart transplant (HTx) patients from 2004 to 2023. Predicted RVMR was calculated for donors and recipients. A parsimonious multivariable model Cox model was formed for risk …

An Innovative Curriculum To Empower Trainees And Faculty To Address Patient-Initiated Identity-Based Misconduct In The Clinical Learning Environment, Nkanyezi Ferguson, Lauren E. Hock, Patrick Barlow, Aisha S. Jamison, Marcy E. Rosenbaum, Nicole Del Castillo

Department of Medicine Faculty Papers

Introduction: Training residents and attending physicians on effective communication strategies to manage biased patient and visitor comments is lacking. The I-RESPOND toolkit curriculum provides strategies for addressing identity-based misconduct in the clinical setting. Methods: Resident physicians and faculty in 12 departments at a single academic center participated in the workshop between June 2021 and February 2022. The workshop consisted of interactive didactics, an introduction to the I-RESPOND toolkit, and opportunities to practice communication strategies with formative feedback. Retrospective pre/postworkshop survey instruments and a follow-up survey were used to evaluate the workshop and subsequent experiences. Results: Sixty-six (32%) of 204 participants …

Evapecognition: An 18-Year Dataset Of Great Ape Cognition, Alejandro Sánchez-Amaro, Sonja J. Ebel Van Wijk, Carin Molenaar, Akzira Abuova, Lizbeth Mujica-Manrique, Sarah M. Leisterer-Peoples, Bret Beheim, Luke Maurits, Anna Albiach-Serrano, Matthias Allritz, Nazli Altınok, Federica Amici, Alice M.I. Auersperg, Filippo Aureli, Elisa Bandini, Jochen Barth, Leïla Benziad, Bettina E. Bläsing, Manuel Bohn, Marie Bourjade, Juliane Bräuer, Marie Hélène Broihanne, Sarah F. Brosnan, Nereida Bueno-Guerra, Thomas Bugnyar, David Buttelmann, Frances Buttelmann, Trix Cacchione, Malinda Carpenter, Fernando Colmenares

School of Psychology

The study of great ape cognition offers insights into the evolutionary origins of human intelligence, but is hindered by small sample sizes and restricted access to data. To address this, we present the EVApeCognition Dataset, a publicly available resource comprising 262 experimental datasets from 150 scientific publications from the Wolfgang Köhler Primate Research Center (2004–2021) in Leipzig, Germany. Eighty-one apes participated in 150 studies, with a majority (N = 78) participating in more than one study. Publication of the dataset aims to make these unique datasets accessible for future meta-analyses and correlational analyses, helping us better understand how our great …

Contraception In The Ed: Understanding Education And Opportunities For Clinicians To Advise Patients, Hannah B. Lewis, Teagan R. Mccarthy, Dara Kass, Jennifer L. Kahoud

Department of Emergency Medicine Faculty Papers

Introduction: The United States faces a high rate of unwanted pregnancies. Despite this, many people continue to face barriers to accessing contraception. The emergency department (ED) can help bridge these gaps, but emergency clinicians must first feel comfortable offering contraceptive services. In this study, we sought to determine emergency clinician comfort in prescribing contraceptives and educating patients on their use. We also gauged clinician interest in receiving education specifically geared toward contraceptive care.

Methods: We conducted an online survey of ED residents, attendings, and advanced practice clinicians at Thomas Jefferson Univerity Hospital and affiliates in both the urban and suburban …

The Effects Of Orexin Receptor Antagonism During Early Withdrawal In Stimulant Use Disorder: Protocol For A Proof-Of-Concept Study, Heather Webber, Nikky Tran, Rita Blake, Sarah Goldman, Trevor George, Bill Bailey, Robert Suchting, Jin Yoon, Jessica Vincent, Michael Weaver, Joy Schmitz, Scott Lane

Faculty, Staff and Student Publications

Background: Stimulant use disorders (StimUDs), including cocaine and methamphetamine use disorders, remain a major public health concern in the United States with no US Food and Drug Administration (FDA)-approved pharmacological treatments. The early recovery period following stimulant use is marked by sleep disturbances, heightened stress reactivity, and dysregulated reward processing, contributing to high rates of resumption of use. Evidence from animal and human studies supports the orexin neuropeptide system as a promising therapeutic target for minimizing these disruptive mechanisms. Suvorexant, an FDA-approved dual orexin receptor antagonist for insomnia, has previously been shown to improve sleep, reduce stress, and attenuate craving …

High-Throughput Multiplex Detection Of Respiratory Pathogens: Multicenter Evaluation Of The Nxtag Respiratory Pathogen Panel V2 Assay., Marisa C. Nielsen, Ping Ren, Sri Bharathi Kavuri, Karissa Culbreath, Rangaraj Selvarangan, Dithi Banerjee, Blake W. Buchan, Rachel Behounek, Janet Farhang

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory tract infections remain a major cause of global morbidity, highlighting the need for rapid and accurate diagnostic testing. This multicenter study evaluated the clinical and analytical performance of the updated NxTAG Respiratory Pathogen Panel v2 (RPPv2), a high-throughput multiplex molecular assay designed to detect 21 viral and bacterial respiratory pathogens. A total of 2,145 nasopharyngeal swab specimens, including both prospectively enrolled and archived specimens, were analyzed across five U.S. clinical sites. The NxTAG RPPv2 was assessed against FDA-cleared molecular assays and bi-directional sequencing, with contrived specimens used to supplement low-prevalence targets. Valid results were obtained for 99.7% of specimens …

Characterization Of Subclonal Variants In Hg002 Genome In A Bottle Reference Material As A Resource For Benchmarking Variant Callers., Camille A. Daniels, Adetola A. Abdulkadir, Megan H. Cleveland, Jennifer H. Mcdaniel, David Jáspez, Luis Alberto Rubio-Rodríguez, Adrián Muñoz-Barrera, José Miguel Lorenzo-Salazar, Carlos Flores, Byunggil Yoo, Sayed Mohammad Ebrahim Sahraeian, Yina Wang, Massimiliano Rossi, Arun Visvanath, Lisa Murray, Wei-Ting Chen, Severine Catreux, James Han, Rami Mehio, Gavin Parnaby, Andrew Carroll, Pi-Chuan Chang, Kishwar Shafin, Daniel Cook, Alexey Kolesnikov, Lucas Brambrink, Mohammed Faizal Eeman Mootor, Yash Patel, Takafumi N. Yamaguchi, Paul C. Boutros, Karolina Sienkiewicz, Jonathan Foox, Christopher E. Mason, Bryan R. Lajoie, Carlos A. Ruiz-Perez, Semyon Kruglyak, Justin M. Zook, Nathan D. Olson

Manuscripts, Articles, Book Chapters and Other Papers

We developed a benchmark set of subclonal variants in the Genome in a Bottle (GIAB) Consortium HG002 reference material (RM) DNA for evaluating lower-frequency variant callsets. We used a somatic variant caller with high-coverage (300×) whole-genome sequencing data from the GIAB Ashkenazi Jewish trio to identify potential subclonal variants in the HG002 RM DNA. Using orthogonal sequencing data and manual curation, we defined a benchmark set with 85 high-confidence subclonal single-nucleotide variants (SNVs) (allele frequency [AF] > 5%) and a benchmark region covering 2.45 Gbp of the autosomes. External validation supported that it can be used to reliably identify both false …

Overlapping Mhc Class I/Ii Epitopes Program Cdc1-Like Differentiation Of Monocyte-Derived Dendritic Cells Via Mtorc1 Signaling Inhibition, S B Amanya, A Murthy, N Bisht, Z N Bullock, K J Ernste, J Vasquez-Perez, W Liu, A Trivedi, D Oyewole-Said, A Paul, L Umokoro, V Akhanov, M Samuel, Z Shi, M H Nguyen, S Huang, M Jeong, P Iakova, K A Jain, K Pham, D C Kraushaar, V Konduri, W K Decker

Faculty, Staff and Students Publications

Viral infection polarizes monocyte-derived dendritic cells (moDC) to initiate type 1 immunity. The availability of overlapping (homologous) MHC class I and II epitopes, an occurrence frequently and primarily associated with intracellular infection, significantly enhances this process; however, the underlying mechanism(s) are unclear. We demonstrate that moDC loaded with homologous MHC epitopes acquire a cDC1-like phenotype in a process governed by mTORC1. mTORC1 pathway inhibition leads to NF-κB-mediated expression of IL-12 and other type I immune polarizing genes. The observed cDC1-like gene signature was also significantly enhanced in clinical moDC vaccine products made through methodologies that enforced class I and II …

What Are The Top 10 Global Research Priorities For Perianal Crohn's Disease? The Global Perianal Crohn's Disease Priority Setting Partnership, Theo Pelly, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Perianal Crohn's disease (pCD) is a debilitating condition with a prevalence of approximately 20% in patients within 10 years of diagnosis of CD. The condition significantly impacts patient quality of life, and there remain a number of unmet needs relating to its optimal management. A global Priority Setting Partnership (PSP) was established to identify the top 10 research priorities for pCD.

METHODS: The PSP followed standard James Lind Alliance (JLA) methodology. An initial survey was circulated to gather unanswered research questions from key stakeholders. From these responses, a longlist of summary questions was formed. These questions were …

Ex Vivo Effect Of Apixaban On Hemostatic Biomarkers In Children With Heart Disease: A Saxophone Trial Substudy, Ghada A Aborkhees, Amy J Barr, Kevin Dietrich, Christoph Male, Zhaoqing Wang, Chen Yao, R Mark Payne, Andrew C Glatz, Paul Monagle, Kristin M Burns, Alison M Reedy, Joshua L Dyme, Peter H Schafer, Antoinette Ajavon-Hartmann, Lesley G Mitchell

2020-Current year OA Pubs

BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin.

METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for …

Relative Impact Of Multidomain Lifestyle Interventions On Deficit Accumulation Frailty Over 24 Months In The U.S. Pointer Trial, Mark A Espeland, Kayloni Olson, Christy C Tangney, Darren R Gitelman, Maryjo Cleveland, Amber A Thro, Yitbarek N Demesie, Heather M Snyder, Rachel A Whitmer, Pankaja Desai, Rifat Alam, Lucia Crivelli, Thomas M Holland, Olivia Preissle, Rema Raman, Michele K York, Laura D Baker

Faculty, Staff and Students Publications

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability …

Untangling Impacts Of Socioeconomic Position, Chronic Disease, And Low-Level Pm2.5 Exposure On Mortality Among Native American Medicare Beneficiaries, Judy Wendt Hess, Wenyaw Chan

Faculty, Staff and Student Publications

Ambient fine particulate matter (PM2.5) is associated with increased mortality at concentrations below current regulatory standards. Studies of low-level exposure often rely on large administrative cohorts whose geographic and demographic composition may influence observed associations. In a prior analysis, we observed an association between long-term PM2.5 and all-cause mortality among Native American Medicare beneficiaries living in zip codes within the lowest decile of PM2.5 exposure. The present study, a case-control analysis of 1,713,399 low-PM2.5-exposed beneficiaries enrolled in traditional Medicare during 2015-2016, evaluated whether this association could be explained by geographic context, socioeconomic position (SEP), or baseline health status. We used …

Translationally-Relevant Tumor Resection Model For Murine Preclinical Models Of Oral Squamous Cell Carcinoma, Gemalene M Sunga, Alejandra Cobos Perez, Andrea H Molina, Nourhan Hussein, Neeraja Dharmaraj, Andrew Sikora, Simon Young

Faculty, Staff and Student Publications

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy. However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to …

Regulation Of Mitochondrial Ros By C15orf48 In A Basal Cell Subpopulation Contributes To Chemotherapy Resistance In Tnbc, Yan Jiang, Noor M Abdulkareem, Amanda L Rinkenbaugh, Yuan Qi, Steven W Wall, Xiaomei Zhang, Jiansu Shao, Sabrina Jeter-Jones, Shirong Cai, Faiza Baameur Hancock, Gloria V Echeverria, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Students Publications

Systemic neoadjuvant chemotherapy, often combined with immunotherapy, is the standard of care for early-stage, non-breast cancer susceptibility gene (BRCA)-mutant triple negative breast cancer (TNBC). However, up to 70% of patients retain residual disease after treatment, which is linked to recurrence and mortality within 5 years. To define mechanisms of resistance, we performed single-cell RNA sequencing on orthotopic TNBC patient-derived xenografts during a cycle of treatment with doxorubicin and cyclophosphamide (AC). Clustering identified four tumor epithelial cell populations, with basal cells enriched in residual tumors. These basal cells up-regulated C15ORF48, a paralog of the mitochondrial cytochrome c oxidase associated subunit FA4 …

Organ Procurement Organization Utilization Of Portable Hypothermic Oxygenated Machine Perfusion In Liver Transplantation: The First Us Experience, Christine E. Haugen, Muhammad Bilal Moeen-Ud-Din, Abdalla M. Hadhoud, Achintya Kaw, James R. Butler, James V. Guarrera, Sherry Quire, Ralph C. Quillin

Department of Surgery Faculty Papers

BACKGROUND: Advanced machine perfusion techniques have increased the use of hard-to-place organs, effectively changing the liver transplantation landscape. Liver transplantation machine perfusion has been driven largely by industry or individual transplant centers. We describe the implementation of a portable, organ procurement organization-initiated hypothermic oxygenated machine perfusion strategy for liver transplantation as a proof of concept.

METHODS: Surgeons and staff at a regional organ procurement organization (Indiana Donor Network) were trained to use and cannulate liver allografts using a portable hypothermic oxygenated machine perfusion platform. We evaluated all liver transplantations recovered and placed on hypothermic oxygenated machine perfusion (N = 18) …