Digital Commons Network^™

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 …

Ms-Gator: Multi-Scale Graph Attention With Topological Reasoning For Segmentation And Classification Of Prostate Cancer Based On Gleason Scores Using Histopathology Images, Sujata Patil, Mahadeva Swamy, Kavitha Sooda, Rajanikanth Vadigepalli, Khalid Nazim Abdul Sattar, Md Rafeeq

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prostate cancer is one of the prevalent and potentially fatal malignancies, affecting men globally. Accurate segmentation and classification of prostate cancer in histopathology images remain challenging due to complex tissue architecture, staining variability, and high inter-observer differences in manual diagnosis. To address these challenges, this research proposes a Multi-Scale Graph Attention with Topological Reasoning (MS-GATOR) for segmentation and classification of prostate cancer based on Gleason Scores (GS). The MS-GATOR incorporates topological reasoning with hierarchical biological structures by constructing a graph-based representation among three spatial scales such as nuclei, glands, and tissues using Delaunay triangulation to capture both geometric and photometric …

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: …

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 …

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 …

Acute Traumatic Aortic Injury: What The Radiologist Needs To Know, Kristina Ramirez-Garcia, Catalina Jaramillo, Emma Ferguson, Jason Au, Erika Odisio, Gustavo S Oderich, Daniel Ocazionez, Cihan Duran, Thanila Macedo

Faculty, Staff and Students Publications

Acute traumatic aortic injury (ATAI) is a rare but life-threatening consequence of blunt trauma that requires prompt diagnosis and accurate imaging assessment. This review presents an imaging-based approach to ATAI, with emphasis on computed tomography angiography (CTA) as the first-line modality for diagnosis, grading, treatment planning, and follow-up. CTA enables the detection of both direct and indirect signs while also allowing for the assessment of lesion severity, extent, and associated findings that may influence management. Familiarity with common mimics and anatomic variants improves diagnostic confidence and helps avoid false positive interpretations. Careful protocol optimization, including multiphasic acquisition, bolus timing, and …

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 …

Cerebellar Oligodendrocytic Α-Synuclein Pathology And Dentate Nucleus Neuronal Hypertrophy In Parkinson’S Disease, Diego Iacono, Hui Peng, John Paul Bouffard, Roger Kurlan

Department of Neurology Faculty Papers

Idiopathic Parkinson's disease (iPD) research has historically prioritized basal ganglia dysfunction and neuronal Lewy body pathology, often overlooking cerebellar and non-neuronal cells contributions. This study investigates cerebellar neuropathology in iPD, specifically focusing on neuronal and non-neuronal cells of the dentate nucleus (DN) and its adjacent white matter (DN-WM). We systematically assessed autopsy-confirmed iPD brains vs. age-matched controls using immunohistochemistry and stereology-based morphometry methods. The study evaluated α-synuclein pathology, other common age-related co-occurring pathologies (β-amyloid, Tau, neuroinflammation), myelin integrity (Luxol-Fast-Blue), and neuronal volumetric changes in the DN of the cerebellum. In iPD brains, we identified intracytoplasmic α-synuclein inclusions within oligodendrocytes across …

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 …

Multi-Trait Polygenic Scores For Copd And Copd Exacerbations Implicate Druggable Proteins, Chengyue Zhang, Iain R Konigsberg, Yixuan He, Jingzhou Zhang, Tinashe Chikowore, William B Feldman, Xiaowei Hu, Yi Ding, Bogdan Pasaniuc, Diana Chang, Qingwen Chen, Jessica A Lasky-Su, Julian Hecker, Martin D Tobin, Jing Chen, Sean Kalra, Katherine A Pratte, Hae Kyung Im, Emily S Wan, Ani Manichaikul, Edwin K Silverman, Russell P Bowler, Leslie A Lange, Victor E Ortega, Alicia R Martin, Michael H Cho, Matthew R Moll

Faculty, Staff and Student Publications

BACKGROUND

We constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.

METHODS

PRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2–4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). …

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 …

Reference Proteins To Improve Core 1 And Core 2 Alzheimer's Disease Csf And Plasma Biomarkers, Linda Karlsson, Nicolas R Barthélemy, Kanta Horie, Suzanne E Schindler, Brian A Gordon, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Concentration-based fluid biomarkers represent an informative and cost-effective way to detect and monitor Alzheimer's disease (AD) pathology. However, non-AD-related interindividual variation in biofluids can also affect biomarker concentrations. Here, we investigated whether normalization of CSF and plasma biomarkers to reference proteins, such as amyloid-β40 (Aβ40) and non-phosphorylated mid-region tau (np-tau), improves their robustness and reliability of representing AD pathology load. Using the Swedish BioFINDER-2 cohort [n = 1702, 50.7% male, mean (standard deviation) age 68.4 (12.2) years], we compared the associations between tau/Aβ-PET load and fluid biomarkers alone versus biomarkers in a ratio with a reference protein (Aβ40 or np-tau) …

Mondo: Integrating Disease Terminology Across Communities., Nicole A Vasilevsky, Sabrina Toro, Nicolas Matentzoglu, Joseph E Flack, Kathleen R Mullen, Harshad Hegde, Sarah Gehrke, Patricia L Whetzel, Yousif Shwetar, Nomi L Harris, Mee S Ngu, Gioconda L Alyea, Megan S Kane, Paola Roncaglia, Eric Sid, Courtney L Thaxton, Valerie Wood, Roshini S Abraham, Maria Isabel Achatz, Pamela Ajuyah, Joanna S Amberger, Lawrence Babb, Jasmine Baker, James P Balhoff, Jonathan S Berg, Amol Bhalla, Xavier Bofill-De Ros, Ian R Braun, Eleanor C Broeren, Blake K Byer, Alicia B Byrne, Tiffany J Callahan, Leigh Carmody, Lauren E Chan, Amanda R Clause, Julie S Cohen, Marcello Deluca, Natalie T Deuitch, May Flowers, Jamie Fraser, Toyofumi Fujiwara, Vanessa Gitau, Jennifer L Goldstein, Dylan Gration, Tudor Groza, Benjamin M Gyori, William Hankey, Jason A Hilton, Daniel S Himmelstein, Stephanie S Hong, Charles T Hoyt, Robert Huether, Eric Hurwitz, Julius O B Jacobsen, Atsuo Kikuchi, Sebastian Köhler, Daniel R Korn, David Lagorce, Bryan J Laraway, Jane Y Li, Adriana J Malheiro, James Mclaughlin, Birgit H M Meldal, Shruthi Mohan, Sierra A T Moxon, Monica C Munoz-Torres, Tristan H Nelson, Frank W Nicholas, David Ochoa, Daniel Olson, Tudor I Oprea, Tomiko T Oskotsky, David Osumi-Sutherland, Kelley Paris, Helen E Parkinson, Zoë M Pendlington, Xiao P Peng, Amy Pizzino, Sharon E Plon, Bradford C Powell, Julie C Ratliff, Heidi L Rehm, Lyubov Remennik, Erin R Riggs, Sean Roberts, Peter N Robinson, Justyne E Ross, Kevin Schaper, Brian M Schilder, Johanna L Schmidt, Elliott W Sharp, Morgan N Similuk, Damian Smedley, Tam P Sneddon, Rachel Sparks, Ray Stefancsik, Gregory S Stupp, Shilpa Sundar, Terue Takatsuki, Imke Tammen, Kezang C Tshering, Deepak R Unni, Eloise Valasek, Adeline Vanderver, Alex H Wagner, Ryan F Webb, Danielle Welter, Doron Yaya-Stupp, Andreas Zankl, Xingmin Aaron Zhang, Julie A Mcmurry, Christopher G Chute, Ada Hamosh, Christopher J Mungall, Melissa A Haendel

Faculty Research 2026

Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠-including identifiers, synonyms, and definitions. To address these …

Claudins Interact With Lilrb Immune Inhibitory Receptors To Promote Myeloid Immunosuppression In Cancer, Xiaoye Liu, Ryan Huang, Zhiqiang Ku, Jingjing Xie, Heyu Chen, Yubo He, Qi Lou, Chengcheng Zhang, Xing Yang, Cheryl Lewis, Jade Homsi, Ankit Gupta, Lei Dong, Kenian Chen, Annabel Tu, Liming Du, Hailong Yu, Qing Hu, Meng Fang, Bufan Li, A E M Adan Khan, Caroline Simith, Samuel John, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

The Brown Foundation: Institute of Molecular Medicine

The mechanisms underlying tumor cell-myeloid cell interactions in the tumor microenvironment (TME) remain unclear, and predictive biomarkers for patient response to myeloid checkpoint blockade are lacking. This study identified specific binding between tight junction claudins (CLDNs) and leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) and LILRB5. In multiple human cancer cohorts, the spatial proximity of LILRB2-positive macrophages to CLDN-expressing cancer cells correlated with clinical outcomes, highlighting this spatial relationship as a potential biomarker. In syngeneic LILRB2-transgenic and humanized mouse models, CLDN18.2-LILRB2 interactions triggered bidirectional signaling, enhanced the immunosuppressive activity of myeloid cells, and accelerated tumor progression. These effects were reversed by …

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 …

Nanog Proximity Proteomics Maps Neighborhood Hubs Linked To Mesenchymal Stem Cell Stemness And Chromatin Control, Kyoung-Jae Choi, Michail Tyryshkin, Harathi Jonnagaddala, Allan Chris M Ferreon, Marian Kalocsay, Josephine C Ferreon

Faculty, Staff and Students Publications

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H2O2 labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and …

Depolymerizing F-Actin Accelerates The Exit From Pluripotency To Enhance Stem Cell-Derived Islet Differentiation, Nathaniel J Hogrebe, Mason D Schmidt, Punn Augsornworawat, Sarah E Gale, Mira Shunkarova, Jeffrey R Millman

2020-Current year OA Pubs

In this study, we demonstrate that cytoskeletal state at the onset of directed differentiation impacts the exit of human pluripotent stem cells (hPSCs) from pluripotency and downstream lineage specification. In particular, depolymerizing F-actin with latrunculin A (latA) during the first 24 h of definitive endoderm formation facilitates efficient loss of pluripotency and alters Activin/Nodal, BMP, c-Jun, and WNT signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved …

Transcultural Headache Medicine: A Framework For Integrating Cultural Contexts Into Headache Science And Care - A Call To Action From The International Headache Society., Mario F. P. Peres, Giancarlo Lucchetti, Homero Vallada, Ivy L. Riso, Georgia K. Westenhofen, Marcelo Moraes Valença, Juliana Ramos De Andrade, K. C. Brennan, Morris Levin, Tsubasa Takizawa, Zhao Dong, Yonggang Wang, Wanakorn Rattanawong, Henry Riyanto Sofyan, Massimo Leone, Freda Dodd-Glover, Hsiangkuo Yuan, Abdulrazaq Albilali, Taoufik Alsaadi, Leonardo Caixeta, Anna P. Andreou, Peter J. Goadsby, Antoinette Maassenvandenbrink, Sait Ashina, Rami Burstein, Patricia Pozo-Rosich, Fayyaz Ahmed, Shuu-Jiun Wang

Department of Jefferson Headache Center Papers and Presentations

Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and …

Systematic Benchmarking Demonstrates Large Language Models Have Not Reached The Diagnostic Accuracy Of Traditional Rare-Disease Decision Support Tools., Justin T Reese, Leonardo Chimirri, Yasemin Bridges, Daniel Danis, J Harry Caufield, Michael A Gargano, Carlo Kroll, Andrew Schmeder, Fengchen Liu, Kyran Wissink, Julie A Mcmurry, Adam S L Graefe, Enock Niyonkuru, Daniel R Korn, Elena Casiraghi, Giorgio Valentini, Julius O B Jacobsen, Melissa Haendel, Damian Smedley, Christopher J Mungall, Peter N Robinson

Faculty Research 2026

Large language models (LLMs) show promise in supporting differential diagnosis, but their performance is challenging to evaluate due to the unstructured nature of their responses, and their accuracy compared to existing diagnostic tools is not well characterized. To assess the current capabilities of LLMs to diagnose genetic diseases, we benchmarked these models on 5213 previously published case reports using the Phenopacket Schema, the Human Phenotype Ontology and Mondo disease ontology. Prompts generated from each phenopacket were sent to seven LLMs, including four generalist models and three LLMs specialized for medical applications. The same phenopackets were used as input to a …

Multiscale Metabolic Covariance Networks Uncover Stage-Specific Biomarker Signatures Across The Alzheimer's Disease Continuum., Juan Antonio K Chong Chie, Scott A Persohn, Ravi S Pandey, Olivia R Simcox, Gregory W. Carter, Paul Salama, Paul R Territo, The Alzheimer’S Disease Neuroimaging Initiative

Faculty Research 2026

INTRODUCTION: Functional connectomics studies leverage the power of interregional brain relationships using graph theory of glycolytic metabolism to establish neural connections and their roles in cognition and disease and to monitor therapeutic responses.

METHODS: Using a retrospective clinical population (N = 431) from ADNI, we evaluated disease changes using metabolic covariance analysis. In addition, we developed a novel region set enrichment analysis (RSEA) to detect brain functional changes based on metabolic variations. Results were aligned with transcriptomic signatures and clinical cognitive assessments (CCAs).

RESULTS: Our findings highlight sexual dimorphic changes across the disease spectrum, which suggest brain network reorganization occurs …

Dental Insurance Status Among Formerly Incarcerated Older Adults, Alexander Testa, Rafael Samper-Ternent, Dylan B Jackson, Kyle T Ganson, Vahed Maroufy, Jason M Nagata, Ana C Neumann

Faculty, Staff and Student Publications

Formerly incarcerated individuals have poorer oral health and less frequent dental care utilization than the general population. However, prior work has overlooked the relationship between prior incarceration and disparities in dental insurance coverage. Using data from the Health and Retirement Study (n = 11,638), findings from multiple logistic regression analyses demonstrate that formerly incarcerated older adults are significantly less likely to have dental insurance coverage (odds ratio [OR] = 0.745, 95% confidence interval [CI] = 0.608, 0.912). After accounting for the income-to-poverty ratio, this association was no longer statistically significant. Analyses using the Karlson-Holm-Breen method demonstrated that approximately 45% of …

Robo2 Variants Associated With Atrial Septal Defect Define A Novel Regulatory Element, Seong Won Kim, Michael Parfenov, Laura Rodriguez-Murillo, David A Conner, Arun Sharma, Inga Peter, Feng Xiao, Olivia Layton, Angela Tai, Tarsha Ward, Lauren K Wasson, Joshua M Gorham, Erica Mazaika, Valentina N Lagomarsino, Tracy L Young-Pearse, Elizabeth Goldmuntz, Hiroko Wakimoto, A J Agopian, David M Mckean, Steven R Depalma, William T Pu, Christine E Seidman, Bruce D Gelb, Jonathan G Seidman

Faculty, Staff and Student Publications

Background: Atrial septal defects (ASDs) are a prevalent type of congenital heart disease. Previous GWAS (Genome-Wide Association Studies) have identified common variants associated with ASDs, though their mechanisms remain unknown. We aimed to expand insights into the architecture of common variants associated with ASD risk and elucidate functional mechanisms.

Methods: We conducted a GWAS using isolated ASD cases and healthy controls and replicated findings in an independent cohort. We examined epigenetic marks within this ASD locus in human induced pluripotent stem cell-derived cardiomyocytes and fetal human hearts. We characterized the consequences of deletions introduced by CRISPR-Cas9 mutagenesis of human induced …

Transfusion In Transit: A Decade Of Prehospital Blood Transfusion In Pediatric Trauma, Krysta M Sutyak, Eunise C Chen, Lea Mock, Rudolfo Cabrera, Jeannette M Joly, Kuojen Tsao, Bryan A Cotton, David E Meyer, Charles S Cox, Kevin P Lally, Natalie A Drucker

The Brown Foundation: Institute of Molecular Medicine

Background: Prehospital blood transfusion improves mortality in adults, with limited evidence in children. This study describes prehospital blood transfusion in pediatric trauma patients and the impact on shock index, pediatric adjusted (SIPA).

Methods: This study is a retrospective cohort study of trauma patients younger than 18 years who received blood transfusions during helicopter transport to a Level 1 pediatric trauma center from 2011 to 2023. Primary outcome was change in SIPA at time of emergency department (ED) arrival with prehospital transfusion. Secondary subgroup analysis was performed based on transport origin.

Results: Of 137 patients, 58% (80 of 137 patients) were …

Natural Language Generation In Healthcare: A Review Of Methods And Applications, Mengxian Lyu, Xiaohan Li, Ziyi Chen, Jinqian Pan, Cheng Peng, Sankalp Talankar, Yonghui Wu

Faculty, Staff and Student Publications

Objective: This study presents a systematic review of natural language generation (NLG) methods and applications in the medical domain, providing quantitative and qualitative analyses to answer four key research questions regarding methods, evaluation, applications, and challenges of NLG in healthcare.

Methods: We searched PubMed, ACM Digital Library, Web of Science, Science Direct, Scopus, Embase, and ACL Anthology for NLG-related studies in healthcare from 2018 to 2024. Out of 3,988 research articles, 113 met the inclusion criteria and were analyzed across data modality, model architecture, evaluation metrics, and application domain.

Results and conclusion: NLG in healthcare has grown substantially, with annual …

Traumatic Brain Injury And Risk Of Early-Onset Dementia: A Population-Based Cohort Study, Aishwarya Saravanan, Katherine Giorgio, Natalia Lakomski, Andrea L C Schneider, Barbara A Olson-Bullis, Behnam Sabayan, James S Pankow, Paul S De Vries, Kristine Yaffe, Alexa Beiser, Abbas Dehghan, Elizabeth A Peterson, Rachel Zmora, John J Stephen, Denise Scholtens, Maxwell Mansolf, Lenore J Launer, Richard F Maclehose, Pamela L Lutsey, Norrina B Allen, Sanaz Sedaghat

Faculty, Staff and Student Publications

Introduction: We investigated the association between traumatic brain injury (TBI) and incidence of early-onset dementia (EOD) versus late-onset dementia (LOD).

Methods: We included 501,710 UK Biobank participants (average age 56.5). Over a median 13.6 years of follow-up, 836 developed EOD (before 65) and 8947 developed LOD (after 65). We estimated hazard ratios (HRs) for TBI's association with EOD and LOD using Cox proportional hazard models with TBI as a time-varying exposure and coefficient.

Results: TBI was associated with higher risk of both EOD (HR: 4.06 [95% confidence interval: 3.13, 5.26]) and LOD (HR: 2.51 [2.31, 2.72]. Among participants included in …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

A Topic Modeling Analysis Of Stigma Dimensions, Social, And Related Behavioral Circumstances In Clinical Notes Among Patients With Hiv, Ziyi Chen, Yiyang Liu, Mattia Prosperi, Krishna Vaddiparti, Robert L Cook, Jiang Bian, Yi Guo, Yonghui Wu

Faculty, Staff and Student Publications

Objective: To characterize stigma dimensions, social, and related behavioral circumstances in people living with HIV (PLWHs) seeking care, using natural language processing methods applied to a large collection of electronic health record (EHR) clinical notes from a large integrated health system in the southeast United States.

Methods: We identified a cohort of PLWHs from the University of Florida (UF) Health Integrated Data Repository and performed topic modeling analysis using Latent Dirichlet Allocation (LDA) to uncover stigma-related dimensions and related social and behavioral contexts. Domain experts created a seed list of HIV-related stigma keywords, then applied a snowball strategy to iteratively …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …