Medical Specialties Commons^™

Cystic Fibrosis Mental Health And Wellness Questionnaire - Factors And Properties Of A Comprehensive Cf-Specific Self-Report Measure, C. Virginia O'Hayer, Patrick J. Smith, Max J. Genecov, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Katherine Lawliss, Darcy C. Esiason, Gunnar H. Esiason

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Existing mental health self-report measures have been criticized for over-simplification, lack of CF-specific focus, susceptibility to measurement reactivity bias, and conflation of symptoms of anxiety and/or depression with CF-related symptoms and/or treatment side effects. The CF Mental Health and Wellness Questionnaire (CFMHWQ) is a 25-item measure assessing CF-specific mental health burden symptoms.

METHODS: To examine common underlying factors contributing to scores on the CFMHWQ, principal component analysis (PCA) was conducted of all 25 items. We conducted cross-validation of CFMHWQ principal components, examining unadjusted correlations between each principal component, demographic characteristics (age and biological sex), negative affect (mean rank global …

Isass Brave New Continuing Medical Education World: The Stifling Of Innovation In Spine Surgery Through Overrestriction Of Collaboration, Morgan P. Lorio, Kai-Uwe Lewandrowski, Óscar L. Alves, Avelino Parajón, Matthew Scott-Young, Hansen A. Yuan, Alex R. Vaccaro

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: in 2020, the accreditation Council for Continuing Medical education (aCCMe) released the Standards for Integrity and Independence in Accredited Continuing Medical Education, effective january 1, 2022, to ensure that accredited activities are accurate, balanced, evidence-based, and clearly separated from marketing and sales. although these aims are broadly supported, implementation may have unintended consequences in procedure-intensive specialties such as spine surgery, where surgeon–industry collaboration often drives device innovation, clinical trials, and dissemination of new techniques.

OBJECTIVE: To examine how current interpretations of ACCME eligibility and financial-relationship standards may affect continuing medical education in spine surgery and to propose practical adaptations …

Tropomyosin-Related Kinase Receptor Type B Agonism In Geographic Atrophy-The Translational Challenges From Preclinical Data To A First-In-Human Trial, David Brown, Oliver Zeitz, Clare Bailey, Sunir J. Garg, Karl Csaky, James Talks, Sobha Sivaprasad, Peter M. Benz, Rolf Herrmann, Remko A. Bakker, Sebastian Bandholtz, Ankit Mittal, Qihong Huang, Serge Kosobokovs, Gudrun Simons, Andrea Giani, Jochen Huber, Martin Gliem

Wills Eye Hospital Papers

OBJECTIVE: To report results of the first-in-human trial of intravitreal tropomyosin-related kinase receptor type B (TrkB) agonist BI 754132 in participants with geographic atrophy (GA). To discuss BI 754132 clinical data in the context of the preclinical findings and their translation into human data.

DESIGN: An open-label, uncontrolled, nonrandomized phase I trial (NCT04002310) assessing the safety, tolerability, and pharmacokinetics of BI 754132 in participants with GA supported by preclinical data.

PARTICIPANTS: Participants with GA recruited between July 2019 and August 2022 in the United States and UK.

METHODS: Clinical trial comprising a single rising dose (SRD) part (n = 15) …

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 …

Personalized Treatment Of Chronic Tendinopathy Using Ultrasound And Neuroimmune Markers: A Narrative Review, Rohan Phadke, Samer Salman, Kirtan Patel, Jad Wardeh, Akhil Marupudi, Rahul Kumar, Arbaz A. Momin, Alireza Tavakkoli

Department of Neurosurgery Faculty Papers

Introduction: : Chronic tendinopathy affects approximately 30% of musculoskeletal consultations, yet treatment outcomes remain inconsistent despite numerous available interventions. This variability stems from the absence of validated frameworks to match individual patients to optimal treatments based on underlying pathophysiology. To synthesize current evidence on ultrasound imaging biomarkers, neuroimmune mechanisms, and interventional therapies in chronic tendinopathy, and propose a clinically applicable framework integrating ultrasound phenotyping with neuroimmune assessment to guide personalized treatment selection. Methods: A systematic literature search was conducted across PubMed, Scopus, and Web of Science through December 2025. Studies examining ultrasound/elastography imaging, neuroimmune mechanisms, or treatment interventions in chronic …

Comparative Effectiveness Of Immunotherapy Alone Or With Chemotherapy As First-Line Treatment For Marginal Zone Lymphoma, Adam Olszewski, Thomas Ollila, Dai Chihara, Geoffrey Shouse, Natalie Grover, Reem Karmali, Pallawi Torka, Colin Thomas, Praveen Ramakrishnan Geethakumari, Stefan Barta, Nancy Bartlett, Narendranath Epperla

Cardeza Foundation for Hematologic Research

No abstract provided.

Unusual Presentation Of Pulmonary Hypertension From Subacute Hyper Viscosity: A Case Report, Jonathan Martin, Tara Rakiewicz, Ubaldo Martinez-Outshoorn, Adam Binder

Jefferson Hospital Staff Papers and Presentations

No abstract provided.

Midwives' Self-Efficacy In Perimenopause Care: An Educational Intervention, Yinka Sokunbi

Doctor of Midwifery Advances in Midwifery Projects

Study Purpose: This project evaluated the effectiveness of an asynchronous continuing education (CE) webinar in improving midwives’ self-efficacy to provide comprehensive perimenopause care.

Research Questions

1. What is the impact of a targeted CE webinar on midwives’ self-efficacy in providing comprehensive perimenopause care?

2. How do participants perceive the impact and acceptability of a pilot CE webinar?

Significance/Background: Despite midwifery’s defined role in lifespan care, engagement in perimenopause management remains limited. Gaps in formal education and continuing professional development contribute to low confidence in this area. Guided by Social Cognitive Theory, this project targeted self-efficacy as a modifiable factor influencing …

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L. Chen, Amanda J. Lu, Rohan Verma, Li Wang, Douglas D. Koch, Allison J. Chen

SKMC Student Presentations and Publications

PURPOSE: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

DESIGN: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

SUBJECTS: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

METHODS: The MC responses were assessed for accuracy …

Aspirin And Preterm Birth Among Pregnant People With Increased Heat Exposure: Secondary Analysis Of A Randomized Clinical Trial, Gabriella Meltzer, Luke Duttweiler, Sarah Saleem, Kartik Shankar, Manolo Mazariegos, Antoinette Tshefu, Jackie Patterson, Elwyn Chomba, Waldemar Carlo, Shivaprasad Goudar, Richard Derman, Archana Patel, Patricia Hibberd, Edward Liechty, Fabian Essamai, Edwin Asturias, Denise Babineau, Janet Moore, Cascade Tuholske, Andrew Zimmer, Brent Coull, Elizabeth Mcclure, Robert Goldenberg, Nancy Krebs, Matthew Hoffman, Blair Wylie

Global Health Articles

IMPORTANCE: Scalable interventions are urgently needed to mitigate the adverse effects of heat on pregnancy and newborn health.

OBJECTIVE: To evaluate whether low-dose aspirin modifies the association between heat exposure and preterm birth.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the Global Network for Women's and Children's Health Research Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) randomized, double-blinded, placebo-controlled clinical trial was conducted from March 2016 to June 2018. Statistical analyses were performed from June 2024 to June 2025. The study settings included the Democratic Republic of Congo, Zambia, Kenya, Guatemala, Pakistan, and Belagavi and Nagpur, …

The First Cut Is The Deepest: Understanding Learner Trauma In The Emergency Medicine Clerkship, Dimitrios Papanagnou, Leela Raj, Karen E. Watkins, Xiao C. Zhang, Andres Fernandez, Md, Victoria J. Marsick

Department of Emergency Medicine Faculty Papers

BACKGROUND: As third-year medical students transition into high-stakes, high-stress clinical environments like the emergency department (ED), they may experience significant personal trauma. However, little is known about how this trauma is experienced early in their training - specifically during the transition from preclinical to clinical learning environments. This study addresses that gap by exploring third-year medical students' experiences of trauma during the emergency medicine (EM) clerkship through the lens of Trauma-Informed Care (TIC) and identifies workplace factors and intersectional demographics influencing these experiences.

METHODS: This qualitative study used the critical incident technique to explore emotionally-significant events encountered by third-year medical …

Population Pharmacokinetics And Dosing Simulations Of Pentobarbital In The Pediatric Population, Victoria Etges Helfer, Lorena Medina-Aymerich, William J. Muller, Marisa Meyer, Amira Al-Uzri, Russell Mcculloh, Chi D. Hornik, Stephen J. Balevic, Rachel G. Greenberg, Daniel K. Benjamin, Sarah G. Anderson, Daniel Gonzalez

Department of Pediatrics Faculty Papers

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: …

Eptinezumab In Treatment-Resistant Chronic Migraine: Four-Year Real-World Effectiveness And Treatment Persistence, Wan-Jen Hsieh, Kelly Nicol, Chai Ching Ng, Tsung-Wei Hou, Phillip Phan, Scott W. Keith, Brittany Heckel, Michael J. Marmura, Hsiangkuo Yuan

Department of Neurology Faculty Papers

AimTo evaluate 48-month real-world outcomes of eptinezumab users in chronic migraine (CM), including longitudinal effectiveness, treatment persistence, reasons for discontinuation, and post-discontinuation anti-calcitonin gene-related peptide (CGRP) treatment patterns.MethodsWe conducted a retrospective cohort study of 112 CM subjects initiating eptinezumab at a tertiary headache center between 2019 and 2021. Monthly headache days (MHD), migraine disability assessment (MIDAS), and average pain intensity (API) were extracted at baseline and every 6 months for up to 48 months using a predefined outcome form at each visit. Longitudinal changes were analyzed using generalized estimating equations (GEE) with an unstructured correlation matrix, adjusting for age, sex, …

Combined Middle Meningeal Artery Embolisation And Subdural Evacuation Port System Drainage For Chronic Subdural Haematoma: A Systematic Review, Single-Arm Meta-Analysis, Meta-Regression, And Cost-Benefit Analysis, Shiva A. Nischal, Santosh Guru, Shaan Patel, Ashviniy Thamilmaran, Mary Murphy

Department of Neurosurgery Faculty Papers

BACKGROUND: Chronic subdural haematoma (cSDH) is an increasingly prevalent condition in older, anticoagulated, and medically frail patients, in whom recurrence and perioperative risk remain substantial despite standard surgical evacuation. Growing recognition of cSDH as an angiogenic, inflammatory disorder has prompted interest in minimally invasive strategies that combine mechanical decompression with targeted modulation of the underlying vascular pathology. This study aimed to evaluate the safety, effectiveness, and health-economic profile of combined middle meningeal artery embolisation and subdural evacuation port system (MMAE-SEPS) drainage for cSDH, compared with conventional burr-hole evacuation.

METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to 24th August …

The Camus Initiative: A Multiphase, Multicentre International Collaboration To Redefine Risk Stratification, Reporting, And Grading Of Surgical Complications In Urology., Christopher Soliman, Niranjan J. Sathianathen, Niall M. Corcoran, Nathan Lawrentschuk, Patrick Y. Wuethrich, Marc A. Furrer, Paul Chung, Camus Study Group Collaborators

Department of Neurology Faculty Papers

Surgical complications remain a major source of preventable morbidity, mortality, and health care expenditure, but existing frameworks such as the Clavien-Dindo classification and Comprehensive Complication Index are clinician-centred and intervention-focused and fail to capture cumulative patient-centred outcomes. This protocol outlines the Complications After Major and Minor Urological Surgery (CAMUS) initiative, a global, multiphase effort to redefine complication reporting, risk stratification, and outcome measurement in urological surgery. CAMUS aims to address these limitations via an integrated, seven-arm programme combining retrospective and prospective data analysis, consensus development, and digital infrastructure design. Arm 1 has assembled a retrospective data set of 130 034 …

Qualitative Beta-2-Adrenoceptor Signaling In The Regulation Of Human Airway Epithelia Mucin And Cytokine Production, Fred Graumuller, Diana Cervantes, Tung O. Chan, Niccolette Schaunaman, Dominic R. Villalba, Burton F. Dickey, Julia K. L. Walker, Hong Wei Chu, Raymond B. Penn

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Numerous in vivo studies have demonstrated beta-2-adrenoceptor (β2AR) -agonism as permissive in the development of allergic lung inflammation, and have implicated the arrestin-dependent signaling arm of the β2AR in mediating this effect. However, the specific cell type(s) mediating β2AR regulation of allergic lung inflammation remain unestablished.

METHODS: To explore the potential contribution of airway epithelia in this phenomenon, we compared the ability of ractopamine (RP), recently identified as a Gs-biased beta-agonist, to that of the unbiased/balanced beta-agonist albuterol (ALB), on IL-13-stimulated mucin and cytokine production in human airway epithelia cultures in air-liquid interface (HAE).

RESULTS: ALB, which activates both …

Knowledge Gaps In High-Energy Sacral Fracture Treatment And Management, Ashraf N. El Naga, Marko H. Neva, Ahmed Abdelazim Hassan, Gregory D. Schroeder, Mohammad El-Sharkawi, Sebastian F. Bigdon, Andrei F. Joaquim, Klaus Schnake, Richard Bransford, Emre Yilmaz

Rothman Institute Papers

High-energy sacral fractures (HESF) are often challenging injuries due to the location of the sacrum at the junction of the spine and pelvis, the complex biomechanics of the pelvic ring and the wide spectrum of injury patterns, which make treatment standardization challenging. Despite advances in classification systems - particularly the AOSpine Sacral Injury Classification - significant gaps remain in understanding optimal management. To review and discuss the management and identify knowledge gaps related to HESF. A narrative review of the literature was conducted, focusing on five domains: 1. Relative instability and biomechanics affected in different injury patterns; 2. The significance …

Reinforcement Learning Improves Llm Accuracy And Reasoning In Disease Classification From Radiology Reports, Yishu Wei, Yi Lin, Adam Flanders, George Shih, Yifan Peng

Department of Radiology Faculty Papers

Accurate disease classification from radiology reports is essential for many applications. While supervised fine-tuning (SFT) of lightweight LLMs improves accuracy, it can degrade reasoning. We propose a two-stage approach: SFT on disease labels followed by Group Relative Policy Optimization (GRPO) to refine predictions by optimizing accuracy and format without reasoning supervision. Across three radiologist-annotated datasets, SFT outperformed baselines and GRPO further improved classification and enhanced reasoning recall and comprehensiveness.

A Systematic Review And Meta-Analysis Finds That Psychological Well-Being Predicts All-Cause Mortality Independently Of Psychological Ill-Being., Max Genecov, David Yeager

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Does psychological well-being (e.g. life satisfaction, happiness, meaning in life) predict the length of a person’s life, or are measures of well-being simply assessing the absence of ill-being (depression, loneliness, sadness) and are therefore redundant with ill-being measures? Individual studies have examined this question by measuring and controlling for both well-being and ill-being, but inconsistent findings have been reported. METHODS: A systematic review and random-effects meta-analysis was conducted on the literature of prospective longitudinal studies linking all-cause mortality to well-being. Studies that controlled for ill-being were compared to studies that did not control for ill-being to identify the unique …

Intraoperative Liposomal Bupivacaine Is Associated With Reduced Opioid Use And Enhanced Recovery After Total Knee Arthroplasty: A Multicenter Registry Study, Mitchell Ng, Jennifer Lin, Andrew Spitzer, Vinod Dasa, Adam Rivadeneyra, David Rogenmoser, Andrew Concoff, Mary Digiorgi, Joshua Urban, William Mihalko, Michael Mont

Rothman Institute Papers

BACKGROUND: With an annual volume of total knee arthroplasties (TKAs) in the United States projected to exceed 1.5 million by 2050, optimizing perioperative pain control and facilitating early discharge remain clinical priorities. This study evaluated the effectiveness of liposomal bupivacaine (LB) vs conventional bupivacaine/ropivacaine in opioid-naïve patients undergoing primary TKA, comparing/contrasting: (1) pain score improvements, (2) opioid usages, (3) functional recoveries, and (4) hospital lengths of stay.

METHODS:  Data from the Innovations in Genicular Outcomes Research (iGOR) registry were used to identify patients undergoing unilateral primary TKA between September 2021 and December 2024. Two hundred twenty-five patients were analyzed, 42 …

High Concordance Of Physician-Attestation With Manual Data Abstraction For Sickle Cell Type: An Ash Rc Data Hub Study, Alexis Thompson, Ashima Singh, Donna Neuberg, Amanda Brandow, Allison King, Sophie Lanzkron, Emily Semmel, Sam Walters, Susan Rogers, Kathleen Torres, William Wood

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The American Society of Hematology Research Collaborative (ASH RC) has built an SCD Data Hub (DH) to facilitate research and quality improvement using real-world data. To our knowledge, we report here the first analyses from the DH, focusing on cohort demographics and accurate identification of SCD diagnosis type. DH sites have data use agreements with ASH RC to extract and transfer electronic health record (EHR) data at least quarterly. Principal investigators (PI) provided additional attestation of SCD diagnosis based on existing local data sources deemed …

Evaluating Glucagon-Like Peptide-1 Receptor Agonist Safety Before Upper Endoscopy: A Systematic Review And Meta-Analysis, Zohaib Ahmed, Amna Iqbal, Sami Ghazaleh, Abdallah Kobeissy, Ali Nawras, Yaseen Alastal, Hani Saad, Sarmed Mansur, Idrees Mohiuddin, Umair Iqbal, Dushyant Singh Dahiya, Syeda Faiza Arif, Connor Campbell, Wade Lee-Smith, Mohammad Asif, Faisal Kamal, Aamir Saeed, Omar Horani

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has remarkably increased in the past few years as they have demonstrated significant reduction in A1c and major cardiovascular outcomes and have led to weight loss with low risk of hypoglycemia. GLP-1 RA use has raised concerns about potential associations with increased gastric retention and adverse outcomes in upper endoscopy procedures.

METHODS: We conducted a comprehensive search across multiple databases to identify comparative studies evaluating the impact of GLP-1 RA exposure versus non-exposure on upper endoscopy outcomes. Studies comparing GLP-1 RAs to other medications were excluded. The primary outcome was …

High-Precision Automated Bone Age: A Clinically Useful Tool In Monitoring Of Treatment Effects In Children And Adolescents, Hans Henrik Thodberg, Lise Aksglaede, Anders Juul, Shanlee M. Davis, Judith L. Ross

Department of Pediatrics Faculty Papers

The clinical value of serial bone age (BA) determinations in children during growth is limited by the manual rater variability (precision 0.63 years). The objective of this work was to determine the precision of automated bone age and bone health index (BHI) measurements by BoneXpert and to establish the time interval at which the automated method can detect a significant treatment effect. The data were from a case-control trial (oxandrolone/placebo) following 90 boys with Klinefelter syndrome (KS) with five visits over 2 years, recording X-rays of both hands. The precision of BA was 0.08 years [0.07; 0.09] 95% CI, leading …

Response Of Reticulocyte And Red Blood Cell Indices To Single-Dose Intravenous Iron In Pregnant Women With Moderate Iron Deficiency Anemia: Secondary Analysis Of The Rapidiron Trial, Manjunath S. Somannavar, Sudhir Mehta, Dharmesh Kumar Sharma, Seema Mehta, Yogeshkumar S, Umesh Charantimath, Benjamin E. Leiby, Michael K. Georgieff, Zubair H. Aghai, Ashalata Mallapur, Umesh Ramadurg, Radha Sangavi, Praveen Patil, J. P. Akshaykirthan, Rupsa C. Boelig, Mrutyunjaya B. Bellad, Richard J. Derman

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Iron deficiency anemia in pregnancy is a significant health concern. Reticulocyte hemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are emerging as early markers, yet their response to different iron therapies in pregnancy is underexplored.

OBJECTIVE: To determine whether intravenous single-dose iron administration produces a more favorable effect on reticulocyte indices than oral iron therapy in anemic pregnant women.

METHODS: This is a secondary analysis of the RAPIDIRON Trial, a multicenter, three-arm randomized controlled trial comparing ferric carboxymaltose (FCM), ferric derisomaltose (FDM) and standard oral ferrous sulfate. Reticulocyte hemoglobin equivalent (Ret-He), Immature Reticulocyte Fraction (IRF) and other red blood …

Disruption Of The Lrrk2 Substrate Rab12 Facilitates Neurotransmission And Causes Hyperactivity In Mice, Xingjian Li, Yuanxin Chen, Huaixing Wang, Xue Zhang, Noah Guy Lewis Guiberson, Xianting Li, Jacqueline Burré, Junmin Peng, Hui Zhang, Zhenyu Yue

Department of Neuroscience Faculty Papers

RAB12 is a small GTPase and a validated substrate of LRRK2, a kinase genetically linked to Parkinson's disease (PD). While RAB12-LRRK2 signaling has been implicated in ciliogenesis and immune regulation, the neuronal function of RAB12 remains largely unexplored. Here, we investigated the role of RAB12 in synaptic physiology using Rab12 knockout (KO) mice. Rab12 KO mice developed normally but exhibited increased locomotor activity in adulthood. Electrophysiological recordings from striatal slices revealed enhanced presynaptic release probability and increased excitatory drive onto medium spiny neurons. Consistently, live-cell imaging of cultured cortical neurons revealed that Rab12 deletion facilitated, while Rab12 overexpression inhibited, synaptic …

Multifocal Papillary Thyroid Carcinoma With Ret P.V804m, Eml4-Alk Fusion, And Braf V600e Positivity, Jacob Beiriger, Leonard Estephan, Lubna Zuberi, Stacey Gargano, Elizabeth Cottrill

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Multifocal papillary thyroid cancer (PTC) can arise from independent primaries with discordant drivers in parallel clonal evolution rather than a single-clone pattern. We present a 31-year-old female with multifocal PTC harboring 3 distinct oncogenic alterations: a germline RET p.V804M mutation, low-frequency EML4-ALK fusion, and BRAF V600E mutation. The RET and ALK alterations were identified in a midpole nodule, whereas BRAF positivity was seen in a separate lower pole tumor. Ultrasound revealed multiple right-lobe thyroid nodules; the dominant 2.1-cm lesion was hypoechoic with calcifications. Fine needle aspiration revealed Bethesda III cytology, prompting thyroid lobectomy and an ipsilateral central neck dissection was …

Inhibition Of Cyclophilin D Rescues Cardiac Function And Bioenergetic Defects Caused By Neonatal Hypoxia, Jonathan R. Burris, Gisela Beutner, Min Yee, Bartholomew V. Simon, Michael F. Swartz, Kathryn B. Boudreau, Ethan D. Cohen, Chaitanya A. Kulkarni, Prottoy Hasan, Hongyue Wang, Karen L. De Mesy Bentley, György Hajnóczky, George M. Alfieris, Eric M. Small, Paul S. Brookes, Michael A. O'Reilly, George A. Porter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Increased oxygen levels at birth regulate myocyte bioenergetic and structural maturation controlled by mitochondrial cyclophilin D (CypD). We evaluated mechanisms of neonatal hypoxic cardiac dysfunction by exposing neonatal mice to 12% oxygen and studied cardiac bioenergetics, myocyte maturation, and function. Hypoxia decreased the activity/assembly of electron transport chain complex I, uncoupled oxidative phosphorylation, increased proliferation, decreased differentiation, increased ventricular mass, and decreased cardiac function. CypD inhibition rescued most hypoxia-mediated effects and increased cardiac function. In conclusion, neonatal hypoxia alters cardiac bioenergetics, myocyte maturation, and cardiac function through CypD-dependent pathways, providing potential therapeutic targets for neonatal cardiac dysfunction.

Speed Of Intravenous Fluid On Glycocalyx Integrity And Central Blood Volume In A Porcine Septic Shock Model, Yosef Levenbrown, Md Jobayer Hossain, Paul T. Fawcett, Marjorie Postell, Anne M. Hesek, Lynell S. Jones, James P. Keith, Thomas H. Shaffer

Department of Pediatrics Faculty Papers

BACKGROUND: It is unclear whether the rate of intravenous fluid (IVF) administration in sepsis influences glycocalyx breakdown. This study aimed to measure the effect of rapid versus slow fluid bolus in a septic pig model on the integrity of the glycocalyx by measuring the serum levels of heparan sulfate and syndecan-1, breakdown products of the glycocalyx. Because endothelial glycocalyx is composed of apical cell membrane-bound proteoglycans such as syndecan-1, covalently bound with long linear glycosaminoglycans such as heparan sulfate, shedding of these different glycocalyx components is closely related. Additionally, we measured central blood volume (blood volume in the heart and …

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 …

Deep Learning And Experimental Validation Of Brca1-Associated Protein-1 Missense Variant Pathogenicity In Uveal Melanoma, Nikhil Davé, David J. Taylor Gonzalez, Mak B. Djulbegovic, Linda A. Cernichiaro-Espinosa, Benjamin A. King, Carol L. Shields, Matthew W. Wilson

Wills Eye Hospital Papers

OBJECTIVE: To benchmark the pathogenicity predictions of AlphaMissense, a deep learning model, against high-throughput functional scores from saturation genome editing (SGE) for all experimentally tested BRCA1-associated protein-1 (BAP1) missense variants in uveal melanoma (UM).

DESIGN: Cross-sectional analytical study comparing computational predictions with experimentally derived functional classifications and clinical annotations.

SUBJECTS PARTICIPANTS AND/OR CONTROLS:  ClusteredAll 4619 BAP1 single amino acid substitutions profiled in a published Regularly Interspaced Short Palindromic Repeats-Cas9 SGE viability assay. No separate control cohort was required. Clinical Variant Database (ClinVar)-annotated variants within this set served as an independent reference.

METHODS: Saturation genome editing log₂-fitness …