Digital Commons Network^™

Resilience Factors And Physical Activity Engagement In Adolescents With Chronic Musculoskeletal Pain: A Cross-Sectional Study., William R. Black, Haley Hart, Jennifer Christofferson, Mark Connelly, Liesbet Goubert, Dustin Wallace, Laura Ellingson-Sayen, Ann M. Davis

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objectives: Chronic musculoskeletal pain (CMSKP) affects up to 40% of adolescents and leads to substantial disability, reduced quality of life, and long-term health risks. Physical activity is central to treatment, but adherence to moderate-to-vigorous physical activity (MVPA) is inconsistent. We evaluated higher-resilience constructs-self-efficacy, pain acceptance, motivational stage, and affect-and hypothesized that higher resilience would be associated with greater objectively measured physical activity, better daily functioning, and higher quality of life in adolescents with CMSKP. Methods: Forty-three adolescents (13-18 years) with CMSKP completed measures of physical activity-specific self-efficacy, acceptance (AFQ-Y), motivational stage (PSOCQ-A), and affect (PANAS-C). Participants wore activPAL …

A Novel Approach To Calculating Expected Total Fetal Lung Volume In Fetuses With Isolated Congenital Diaphragmatic Hernia And Fetal Growth Restriction: A Theoretical Computational Simulation, Morcos Hanna, Jonathan Davies, Amaryllis Fernandes, Pamela M Ketwaroo, Amy R Mehollin-Ray, Roopali Donepudi, Alice King, Joseph Hagan, Sundeep G Keswani, Sharada H Gowda, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Predicting Intravitreal Treatment Response Using Ultrawide-Field Angiographic Biomarkers In Diabetic Retinopathy, Karthik Reddy, Callie Deng, Boonkit Purt, Yue Liang, Nikhil Bommakanti, Gina Yu, Julie Rosenthal, Yannis M. Paulus

Wills Eye Hospital Papers

BACKGROUND: Diabetic retinopathy (DR) is a sight-threatening retinal disease with pathological mediation by vascular endothelial growth factor (VEGF). Intravitreal anti-VEGF injections are commonly used to manage DR. Ultra-wide-field fluorescein angiography (UWF-FA) can assess DR severity and characterize the amount of non-perfused retina (non-perfusion area, NP), neovascularization (neovascular area, NV), and foveal avascular zone (FAZ). However, the association between anti-VEGF treatment and NP, NV, and FAZ characterized by UWF-FA is not well established.

METHODS: A retrospective, single-center cohort study involved eyes of patients with Type 1 or 2 diabetes mellitus with at least one UWF-FA image. The area of the FAZ, …

Human Papillomavirus Vaccine Uptake In Ethnically Diverse Women Living With Systemic Lupus Erythematosus, Sebastian Bruera, Yinan Huang, Savannah Bowman, Maria E Suarez-Almazor, Grace H Lo, Maria A Lopez-Olivo, Elizabeth Chiao, Jennifer R Kramer, Frederick A Pereira, Sandeep K Agarwal

Faculty, Staff and Students Publications

Background: Women with systemic lupus erythematosus (SLE) are at an increased risk of infection from the human papillomavirus (HPV) and subsequently HPV-mediated malignancies and genital warts. The HPV vaccine is a highly effective intervention in preventing HPV infection and is recommended in SLE patients. We determined HPV vaccination rates and factors associated with decreased vaccination uptake in women living with SLE.

Methods: We conducted a cross-sectional study in which we enrolled women with SLE (aged 21–45) for whom the HPV vaccine is recommended for by the US Food and Drug Administration (FDA). The primary outcome was self-reported HPV vaccination as …

Branch Retinal Artery Occlusion After Covid-19, Danielle Kalberer Od, Mba, Grace Tan Od

Optometric Clinical Practice

Background: A healthy, 39-year-old male patient presented with sudden onset, painless vision loss of the right eye’s superior visual field two months after a mild case of COVID-19.

Case Report: The patient was diagnosed with an acute branch retinal artery occlusion and referred to the emergency department for prompt evaluation. When the emergency workup was unremarkable the patient was referred to cardiology and hematology and follow up with a retinal specialist. The exhaustive systemic work-up was unremarkable other than recent COVID-19. Retinal perfusion to the affected area resumed in the weeks after the incident but irreversible vision loss occurred.

Conclusion: …

Modeling Surgeon Belief Updating Under Bias: A Bayesian Simulation In Shoulder Arthroplasty, Mariano Menendez, Michael Moverman, Surena Namdari, Frederick Matsen, David Ring

Rothman Institute Papers

BACKGROUND: Shoulder surgeons often offer markedly different treatment recommendations for a given patient and pathophysiology within the context of a common body of evidence. Prior beliefs and cognitive bias may contribute to this variability. Using Bayesian decision theory informed by principles of behavioral science, we modeled how surgeons with different initial beliefs and degrees of bias update their treatment preferences in response to new evidence comparing anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) when making surgery recommendations for advanced primary glenohumeral osteoarthritis.

METHODS: We developed a Bayesian simulation involving 3 hypothetical surgeons with distinct initial beliefs: …

The Mycancergene Study: A Hybrid Type 1 Effectiveness-Implementation Randomized Study Comparing A Patient-Centered Digital Genetic Health Portal To Usual Care After Receipt Of Cancer Genetic Testing, Daniel Chavez-Yenter, Dominique Fetzer, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Kelsey Karpink, Lauren Gutstein, Shelby Posen, Enida Selmani, Briana Mcleod, Arravinth Anantharajah, Sarah Brown, Cara Cacioppo, Jacqueline Cappadocia, Jessica Ebrahimzadeh, Dana Falcone, Sarah Howe, Claire Langer, Beth Mccarthy-Wood, Michelle Weinberg, Angela Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: Genetic testing has become more complex with the transition from single gene testing to multi-gene panels and whole-exome sequencing. The adoption of more complex genetic testing and the promise of precision medicine has created a critical and urgent need for longitudinal clinical follow-up with patients who undergo cancer genetic testing given the residual uncertainty. There is an increasing need for multidisciplinary translational research that focuses on how to advance precision medicine discoveries into clinical practice and to capitalize on connectivity (e.g. digital health) interventions in ways that optimize cancer risk reducing behaviors in real-world clinical populations.

METHODS: The overall …

Perfusion Assessment In Ceus Imaging For Estimating Pancreatic Cancer Response To Sonoporation-Enhanced Chemotherapy., Omri Adler, Priscilla Machado, Trang Vu, Flemming Forsberg, Odd Helge Gilja, Dan Adam

Department of Radiology Faculty Papers

Accurate assessment of perfusion in vital organs like the pancreas is crucial for monitoring various pathologies, particularly tumors and their growth. While tumor growth inhibition usually results in decreased vascularization, current techniques for non-invasive and cost-effective perfusion assessment lack sufficient vessel separability for pancreatic applications, hindering optimal treatment selection and monitoring. Ultrasound (US) imaging offers advantages like low cost, rapid acquisition, non-invasiveness, and non-ionizing radiation. However, speckle, patient-related and acquisition-related motion artifacts, and limitations in distinguishing contrast-enhanced blood vessels, particularly in single frames, pose significant challenges. This study presents a novel solution utilizing image analysis of US contrast agents (UCAs) …

Transdiagnostic Alterations In White Matter Microstructure Associated With Suicidal Thoughts And Behaviours In The Enigma Suicidal Thoughts And Behaviours Consortium, Laura S Van Velzen, Lejla Colic, Zuriel Ceja, Maria R Dauvermann, Luca M Villa, Hannah S Savage, Yara J Toenders, Niousha Dehestani, Alyssa H Zhu, Adrian I Campos, Lauren E Salminen, Martin Alda, Ingrid Agartz, Nina Alexander, Rosa Ayesa-Arriola, Elizabeth D Ballard, Nerisa Banaj, Carlotta Barkhau, Zeynep Başgöze, Jochen Bauer, Francesco Benedetti, Klaus Berger, Bianca Besteher, Katharina Brosch, Manuel Canal-Rivero, Simon Cervenka, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Philippe Courtet, Baptiste Couvy-Duchesne, Benedicto Crespo-Facorro, Kathryn R Cullen, Udo Dannlowski, Jeremy Deverdun, Ana M Diaz-Zuluaga, Lorielle M F Dietze, Jennifer W Evans, Negar Fani, Kira Flinkenflügel, Naomi P Friedman, Ian H Gotlib, Nynke A Groenewold, Dominik Grotegerd, Tomas Hajek, Alexander S Hatoum, Marco Hermesdorf, Ian B Hickie, Yoshiyuki Hirano, Tiffany C Ho, Yuki Ikemizu, Frank Iorfino, Jonathan C Ipser, Yuko Isobe, Andrea P Jackowski, Fabrice Jollant, Tilo Kircher, Melissa Klug, Sheri-Michelle Koopowitz, Anna Kraus, Axel Krug, Emmanuelle Le Bars, Elisabeth J Leehr, Meng Li, Elizabeth T C Lippard, Carlos Lopez-Jaramillo, Ivan I Maximov, Andrew M Mcintosh, Katie A Mclaughlin, Sean R Mcwhinney, Susanne Meinert, Elisa Melloni, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Stener Nerland, Emilie Olie, Victor Ortiz-García De La Foz, Pedro M Pan, Fabricio Pereira, Fabrizio Piras, Federica Piras, Sara Poletti, Andrew E Reineberg, Gloria Roberts, Rafael Romero-García, Matthew D Sacchet, Giovanni A Salum, Anca-Larisa Sandu, Carl M Sellgren, Eiji Shimizu, Harry R Smolker, Jair C Soares, J Douglas Steele, Frederike Stein, Dan J Stein, Benjamin Straube, Lea Teutenberg, Florian Thomas-Odenthal, Paula Usemann, Romain Valabregue, Johanna Valencia-Echeverry, Gerd Wagner, Gordon Waiter, Martin Walter, Heather C Whalley, Mon-Ju Wu, Tony T Yang, Carlos A Zarate, Andre Zugman, Giovana B Zunta-Soares, Kees Van Heeringen, Sanne J H Van Rooij, Nic Van Der Wee, Steven Van Der Werff, Paul M Thompson, Hilary P Blumberg, Anne-Laura Van Harmelen, Miguel E Rentería, Neda Jahanshad, Enigma Suicidal Thoughts And Behaviours Consortium, Lianne Schmaal

Faculty, Staff and Student Publications

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we examined WM alterations associated with STBs. Data processing was standardised across sites, and resulting WM microstructure measures (fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity and radial diffusivity) for 24 WM tracts and one global measure were pooled across 40 cohorts. We compared these measures among individuals with a psychiatric diagnosis and lifetime history of …

Leptin As A Key Driver For Organ Fibrogenesis, Xue-Nan Sun, Shiuhwei Chen, Shangang Zhao, Jan-Bernd Funcke, Megan Virostek, Line Pedersen, Chao Li, Chanmin Joung, Qian Lin, Yan Li, Ayanna Cobb, May-Yun Wang, Kyounghee Min, Lisandro Maya-Ramos, Giovanna Degasperi, Junquan Liu, Ningyan Zhang, Zhiqiang An, Diana R Tomchick, R Max Wynn, Da Young Oh, Philipp E Scherer

Faculty, Staff and Student Publications

Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting …

Lorbin: Efficient Binning Of Long-Read Metagenomes By Multiscale Adaptive Clustering And Evaluation, Wei Xue, Zuo Liu, Yaozhong Zhang, Waseem Raza, Yarong Li, Li Jiang, Ye Tao, Jun Qian, Jousset Alexandre, Fang-Jie Zhao, Yangchun Xu, Fritz Sedlazeck, Qirong Shen, Gaofei Jiang, Zhong Wei

Faculty, Staff and Students Publications

Long-read sequencing has transformed metagenomics and improved the quality of metagenome-assembled genomes (MAGs). However, current binning methods struggle with identifying unknown species and managing imbalanced species distributions. Here, we present LorBin, an unsupervised binner specially designed to reconstruct MAGs in natural microbiomes. LorBin deploys a two-stage multiscale adaptive DBSCAN and BIRCH clustering with evaluation decision models using single-copy genes to maximize MAG recovery. LorBin outperforms six competing binners in both simulated and real microbiomes, including oral, gut, and marine samples. LorBin generated 15-189% more high-quality MAGs with high serendipity and identified 2.4-17 times more novel taxa than state-of-the-art binning methods. …

Profound Opioid And Medetomidine Withdrawal: A Case Series And Narrative Review Of Available Literature, Phil Durney, Elise Paquin, Gamal Ftizpatrick, Drew Lockstein, Tareva Warrick-Stone, Do, Maeve Montesi, Sejal Patel, Jamal Rashid, Oluwarotimi Vaughan-Ogunlusi, Kelly Goodsell, Jennifer L. Kahoud, Christopher Martin, Keira Chism, Paul Goebel, Karen Alexander, Dennis Goodstein, Kory S. London

Division of Internal Medicine Faculty Papers & Presentations

Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.

Rtx-303, An Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates Parp Inhibitors In Brca Mutant Tumors, Gurushankar Chandramouly, William Fried, John Gordon, Douglas Ralph, Channita Keuk, Sangeeta Kumari, Mercy Ramanjulu, William Auerbacher, Leonid Minakhin, Taylor Tredinnick, Bernadette Tiberi, George Morton, Robert Betsch, Kathy Q. Cai, Umeshkumar M Vekariya, Mrityunjay Tyagi, Tomasz Skorski, Sergey Karakashev, Neil Johnson, Wayne E. Childers, Xiaojiang S. Chen, Richard T. Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase θ (Polθ) is a polymerase-helicase fusion protein that is synthetically lethal with homologous recombination (HR) factors, such as BRCA1/2, and confers resistance to PARP inhibitors (PARPi) and other genotoxic cancer therapies. Previously developed Polθ polymerase (Polθ-pol) inhibitors (Polθi) exhibited limited pharmacological activity and metabolic stability, warranting the development of a Polθi with improved drug-like properties. Here, we developed RTx-303, a selective allosteric small-molecule Polθ-pol inhibitor that exhibits 5.1 nM IC50, 88% oral bioavailability, and a prolonged half-life along with its equipotent metabolite. X-ray crystallography highlights the development of a solvent-exposed side-chain that is essential for the optimal drug-like …

Genome-Wide Association Study Of Childhood B-Cell Acute Lymphoblastic Leukemia Reveals Novel African Ancestry-Specific Susceptibility Loci, Cindy Im, Andrew R Raduski, Lauren J Mills, Kashi Raj Bhattarai, Robert J Mobley, Kelly R Barnett, Zhanni Lu, Kenneth Liao, Nathan Anderson, Rebecca A Johnson, Erica Langer, Anthony J Hooten, Alix E Seif, Kathrin M Bernt, Matthew Tsang, Brandon A Mamou, Luis Gil-De-Gómez, Julie A Wolfson, Danielle N Friedman, Neerav Shukla, Laura J Klesse, Erin L Marcotte, Lingyun Ji, Alice Dang, Minjie Luo, Yiming Zhong, Jalen Langie, Charleston W K Chiang, Adam De Smith, Joseph L Wiemels, Andrew Dewan, Xiaomei Ma, Catherine Metayer, Zhaoming Wang, Heather H Nelson, Nathan Pankratz, Tianzhong Yang, Saonli Basu, Lucie M Turcotte, Jun J Yang, Daniel Savic, Michael E Scheurer, Logan G Spector

Faculty, Staff and Students Publications

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance (P <  5 × 10−8) after meta-analysis. Two loci were established trans-ancestral susceptibility regions (IKZF1, ARID5B), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P = 4.8 × 10−3). Novel risk variants were also associated with subtype-specific disease (P <  0.05), including higher susceptibility for a subtype overrepresented in African American children (TCF3-PBX1) and lower …

Association Between End-Of-Third-Year Objective Structured Clinical Examinations And Accreditation Council For Graduate Medical Education Milestones During Intern Year, Katherine Berg, Jillian Zavodnick, Dianna Cheney-Peters, Heather Heiman, Sally Santen, Yoon Soo Park, Anita Wilson

Department of Medicine Faculty Papers

BACKGROUND: The Objective Structured Clinical Examinations (OSCEs) administered in medical schools have increased in importance with the elimination of United States Medical Licensing Exam (USMLE) Step 2 Clinical Skills (CS).

OBJECTIVE: The purpose of this study was to understand the association between student performance on an end-of-third-year OSCE and performance in residency.

METHODS: This study explored the correlations between OSCE performance and relevant Accreditation Council for Graduate Medical Education (ACGME) milestone 1.0 performance. This study included students’ scores from 139 Sidney Kimmel Medical College (SKMC) students who completed an end-of-third-year OSCE during 2015 and 2016 and completed an intern year …

Defining Endotypes Of Bronchopulmonary Dysplasia In Preterm Infants To Improve Precision-Based Therapies., Megha Sharma, Gangaram Akangire, Noah H. Hillman, Winston M. Manimtim, Mark Ivan Attard, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) remains a debilitating disease in premature infants. The chronic pathogenesis of BPD with complex prenatal and postnatal programming challenges attempts at precisely defining or treating disease. While existing BPD definitions categorize disease severity, a lack of consideration of disease heterogeneity and endotypes has contributed to the failure of clinical trials to improve BPD outcomes. Recent studies have used advanced lung imaging techniques, echocardiography, and lung function tests to identify airway, parenchymal, and vascular BPD endotypes. These endotypes carry different prognoses and require endotype-specific treatment strategies to optimize infant outcomes. In this Review, we focus on the pathogenic …

Influences On Emergency Clinician Use Of Health Information Exchange: Interview Study, Brian E. Dixon, Umesh Ghimire, Benjamin Richter, Corinne Bowditch, Saurabh Rahurkar, John T. Finnell, Joshua R. Vest

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Health information exchange (HIE) supports clinical decision-making in emergency medicine settings. Despite evidence and policies that encourage the adoption of HIE, use by clinicians is limited. Moreover, few studies examine HIE use years after adoption by hospitals or clinics.

OBJECTIVE: This study aims to examine the perceptions and use of a mature, operational HIE system by emergency department clinicians years after its implementation.

METHODS: We interviewed 21 clinicians in various roles (eg, attending physician and nurse practitioner) across multiple health systems that participate in a statewide HIE network. We asked questions about their use of the HIE system and …

Biallelic Loss-Of-Function Variants In C19orf44 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen

Faculty, Staff and Students Publications

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to …

Global Burden Of 292 Causes Of Death In 204 Countries And Territories And 660 Subnational Locations, 1990–2023: A Systematic Analysis For The Global Burden Of Disease Study 2023, Gbd 2023 Causes Of Death Collaborators

Faculty, Staff and Students Publications

Background: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of …

Cep76 Impairment At The Centrosome-Cilium Interface Contributes To A Spectrum Of Ciliopathies, Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A Lewis, Farid Ullah, Thomas Arbogast, Jackson P Ogden, Madeleine Harion, Marjolaine Willems, Maha S Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E Davis

Faculty, Staff and Students Publications

Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76, encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including …

Metabolic Impact Of Dietary Glycine Supplementation In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Paul M Yen, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine plays a central role in human metabolism, and an adequate supply is required for synthesizing glutathione (GSH), eliminating excess metabolites as acylglycine via the glycine conjugation detoxification pathway, and maintaining 1-carbon cycle activity. However, glycine is deficient in individuals with severe obesity, which may compromise these pathways and metabolic health. This exploratory study examines whether dietary glycine supplementation could correct glycine deficiency and impairments in glycine-dependent metabolic pathways. 19 participants with severe obesity (BMI 38.3 ± 5.3 kg/m2) were treated with dietary glycine (100 mg/kg/day) for two weeks. We found that treatment significantly increased the plasma concentration of glycine …

Assessing The Cardiac Safety Of A Multimodal Protocol For 'Tranq Dope' Withdrawal: A Retrospective Qtc Analysis, Kory London, Emily Deschler, Sabrina Butt, Steven Graver, Jake Figaniak, Nathan Hersh, Ariana Rucker, Bogdan Popa, Jenna Hoopes, Jennifer Kahoud, Behzad Pavri

Department of Emergency Medicine Faculty Papers

BACKGROUND: "Tranq dope"-fentanyl adulterated with xylazine-has complicated the management of opioid withdrawal in emergency departments (EDs). A novel withdrawal protocol was implemented to address these challenges, utilizing concurrent agents to intentionally synergize and potentiate effects. Questions remain about the safety of its components, some of which may prolong the QT interval.

METHODS: We conducted a retrospective cohort study of adult ED patients with suspected fentanyl/xylazine exposure treated utilizing novel protocol across two urban hospitals in Philadelphia, PA between September 2022 and October 2024. Patients with both pre- and post-treatment electrocardiograms (ECGs) were included. QTc intervals were reviewed by an experienced …

Interventions To Minimize Unnecessary Antibiotic Use For Acute Otitis Media: A Meta-Analysis., Theresa L. Morin, Amy B. Stein, Rana El Feghaly, Amanda Nedved, Sophie E. Katz, Amy Keith, Heather E. Laferriere, Timothy C. Jenkins, Holly M. Frost

Manuscripts, Articles, Book Chapters and Other Papers

Backgrounds/Objectives: Acute otitis media (AOM) is the leading reason antibiotics are prescribed to children. Despite guidelines advocating for watchful waiting and shorter antibiotic durations, overprescribing remains a concern. This meta-analysis aims to quantify potential reduction in antibiotic days of therapy (DOT) for AOM if prescribers adhered to guidelines. Methods: Cochrane databases were sourced for studies on ear infections, diagnostic accuracy, antibiotic duration, and watchful waiting. Randomized clinical trials, observational studies, and quality improvement reports of children aged 6 months-17 years with uncomplicated AOM published between 2000 and 2024 from the U.S., Canada, and Europe. Of 4187 studies, 425 met selection …

Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley

Children’s Nutrition Research Center Staff Publications

Background: Medical nutrition therapy is fundamental for managing glycemia and weight in type 1 diabetes, yet dietary guidance specific to this population and relevant subgroups is lacking.

Purpose: We synthesized the interventional literature investigating diet patterns for glycemic and weight management in youth and adults with type 1 diabetes, with attention to interindividual variation that suggests the need for precision approaches. The protocol was prospectively registered (CRD42024519941).

Data sources: AMED, CINAHL, Cochrane Library, Ovid MEDLINE, Ovid Embase, Google Scholar, and Web of Science Core Collection were searched from January 2011 to June 2024.

Study selection: Clinical trials ≥4 weeks with …

Implementation Evaluation Of Blood Flow Restriction In The Rehabilitative Setting, Corbit Franks, Madison Wellborn, Matthew A. Chatlaong, Daphney M. Carter, William M. Miller, Matthew B. Jessee, Robert E. Davis

Internet Journal of Allied Health Sciences and Practice

Purpose: Blood flow restriction refers to a training/rehabilitation method consisting of an external pressure system applied to a limb to partially inhibit blood flow to the tissues. Though much research has been conducted concerning the use of blood flow restriction, there is limited research concerning why clinicians may or may not utilize it. Objective: The current qualitative study utilized the Consolidated Framework for Implementation Research to investigate why clinicians may or may not implement blood flow restriction in the clinical setting. Methods: A semi-structured interview addressing twelve implementation constructs within four domains (Intervention Characteristics, Outer Setting, Inner Setting, and Characteristics …

A Case Series: Effectiveness Of Nintendo Ring Fit In Improving Balance And Stability Deficits After Recovery From Acl Reconstruction, Emma C. Lord, Melissa A. Tolbert, Whitley J. Stone

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 6: Issue 1, Article 10, 2025. This study aimed to assess the effectiveness of a gaming system in improving balance, strength, and power after recovery from an anterior cruciate ligament reconstruction (ACLR). Existing bilateral deficits were also assessed among patients.

Four participants between the ages of 18-24 years were recruited for this case-control study. Participants must have had an ACLR in the last 2 years, been discharged from formal physical therapy, and have a continued history of participating in physical activity at least three times a week. Participants were assigned to either the …

Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan

Wills Eye Hospital Papers

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we …

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …