Digital Commons Network^™

Genetic Associations With Pulmonary Embolism Among Those With A Deep Vein Thrombosis: The International Network Against Venous Thrombosis Consortium, Susana Lozano-Esparza, Gabrielle E Shakt, Jennifer A Brody, Angel Martinez-Perez, Matthew P Conomos, Marine Germain, Katharine R Clapham, Maris Teder-Laving, Astrid Van Hylckama Vlieg, Anni Kauko, Florian Thibord, Ohanna C L Bezerra, Girish N Nadkarni, Gaëlle Munsch, Therese Haugdahl Nøst, Ellen L Goode, Yuekai Ji, Daniel I Chasman, Alexander P Reiner, Constance Turman, Kerri L Wiggins, Colleen M Sitlani, Juan Carlos Souto, Pamela L Lutsey, Tiffany Bellomo, Estonian Biobank, Million Veteran Program, Ruifang Li-Gao, Aleksi Kristian Winstén, Ming-Huei Chen, Ron Do, Lénaick Gourhant, Kristian Hveem, Sebastian M Armasu, Noémie Saut, Nathan Pankratz, Franco Giulianini, Jeffrey Haessler, Mingyang Song, Robert Olaso, Eric Boerwinkle, Daniel Dochtermann, Jose Manuel Soria, Stephen S Rich, David Smadja, Satoshi Koyama, Frits R Rosendaal, Teemu Niiranen, France Gagnon, Ha My T Vy, Neil Zakai, Catherine Lemarie, Anne Heidi Skogholt, Jean-François Deleuze, James S Pankow, Paul M Ridker, Yuxi Liu, Kenneth M Rice, Saiju Pyarajan, Mary Cushman, Jospeh Emmerich, Bruce M Psaty, Pradeep Natarajan, Andrew D Johnson, Marc A Rodger, Pierre Suchon, Francis Couturaud, Pierre-Emmanuel Morange, Weihong Tang, Charles Kooperberg, Christopher Kabrhel, Maria Sabater-Lleal, David-Alexandre Trégouët, Alisa S Wolberg, Scott M Damrauer, Nicholas L Smith

Children’s Nutrition Research Center Staff Publications

Background: Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE), the latter of which often originates from DVT and can be fatal.

Objectives: The aim of this study was to identify causal genetic factors that alter risk of PE among those with a presumed DVT.

Methods: Using a case-only design of VTE, we conducted meta-analyses of genome-wide association studies (GWASs) in the International Network Against Venous Thrombosis Consortium. Among participants diagnosed with VTE, each study identified those who had a clinically reported PE, with or without a clinically reported DVT; those remaining had isolated DVT. Logistic regression …

Dupilumab For Patients With Allergic Fungal Rhinosinusitis, Amber U Luong, Joshua M Levy, Sarah K Wise, Joseph K Han, Mamoru Yoshikawa, Luo Zhang, Rodney Schlosser, Prerna Ranganathan, Paula Dakin, Jennifer Maloney, George D Yancopoulos, Andrew P Fontenot, Neelam A Phadke, Lacey R Robinson

The Brown Foundation: Institute of Molecular Medicine

Background: Allergic fungal rhinosinusitis (AFRS) is a severe subtype of chronic rhinosinusitis characterized by fungal hypersensitivity and accentuated type 2 inflammation. Dupilumab-a fully human mAb blocking IL-4/13, approved for type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps-may benefit patients with AFRS.

Objective: We sought to understand the effect of dupilumab in AFRS.

Methods: In this phase 3 trial, patients with AFRS age ≥6 years were randomized to dupilumab or matched placebo for 52 weeks. The primary end point was Lund-Mackay computed tomography score, quantifying sinus opacification, at 52 weeks. Secondary end points were multiplicity-controlled and hierarchically tested.

Results: …

Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie

Faculty, Staff and Student Publications

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing …

Rsv Can Infect The Human Nasal Epithelium Via The Basolateral Route And Shows Distinct Subgroup Infectivity And Basal Cell Tropism, Ashley Murray, Divya Nagaraj, Emily M Schultz, Gina Aloisio, Erin Nicholson, Sarah E Blutt, Vasanthi Avadhanula, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) causes millions of lower respiratory tract infections (LRTIs) in young children, older adults, and immunocompromised populations every year. RSV infection initiates in the upper respiratory tract and can progress to the lower airways, resulting in bronchiolitis, pneumonia, and even death. RSV primarily infects epithelial cells apically, but we hypothesized that basolateral exposure of the respiratory epithelium could provide an alternative mechanism of infection that contributes to LRTI development. Using a human nose organoid-air-liquid interface (HNO-ALI) model, we performed apical and basolateral inoculations with contemporaneous RSV strains (RSV/A/Ontario [RSV/A/ON] and RSV/B/Buenos Aires [RSV/B/BA]) representing the two RSV …

Loss Of Atp-Dependent Citrate Lyase Drives Left Ventricular Dysfunction By Metabolic Remodeling, Shijie Liu, Seth T Gammon, Lin Tan, Yaqi Gao, Kyoungmin Kim, Mahmoud H Elbatreek, Adrian Arrieta, Ian K Williamson, Rebecca L Salazar, Janet Pham, Angela Davidian, Radhika Khanna Neicheril, Benjamin D Gould, Heidi Vitrac, Alia Sadiq, An Q Dinh, Evan C Lien, Francisca N De Luna Vitorino, Joanna M Gongora, Sara A Martinez, Melanie T Odenkirk, Anna K Boatman, Jessie R Chappel, Lawrence S C Czer, Evan P Kransdorf, David J Lefer, Blake M Hanson, Benjamin A Garcia, Erin M Baker, Matthew G Vander Heiden, Philip L Lorenzi, Heinrich Taegtmeyer, David Piwnica-Worms, James F Martin, Anja Karlstaedt

Faculty, Staff and Student Publications

Background: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated.

Methods: We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced …

Molecular Mechanism Leading To Human Coronary Atherosclerosis Assessed By Proteomic Analysis And Rna Sequences, Sarah J Parker, Chunhong Mao, David L Caudell, Austin Lyle Seals, Yizhi Wang, Thomas D Green, Joseph M Mcclung, Joshua T Maxwell, Jacolby T Roddey, Kiarash Shakeriastani, Chiung-Ting Wu, Yingzhou Lu, Do-Kyun Kim, Justyna Fert-Bober, Dongping Du, Archana Bhat, Niveda Sundararaman, Matthew Ayres, Rakhi Pandey, Saurabh Bhardwaj, Genesio M Karere, Dana Troxclair, Fannie Jackson, Gordon L Love, Richard Vander Heide, James Hixson, Jennifer E Van Eyk, Yue Wang, David Herrington

Faculty, Staff and Student Publications

Background and aims: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt …

Overcoming Igf1r-Mediated Resistance To Oncolytic Hsv1 And Radiotherapy Via Triple Combination Therapy, Alexandra A Miller, Min-Hye Noh, Jin Muk Kang, Jiyeon Kim, Lily Nguyen, Amanda S Kouaho, Grace Nguyen, Minxin Huang, Stephanie M Bean, Joshua Davis, Matthew P Mullarkey, Sunil Krishnan, Zhongming Zhao, E Antonio Chiocca, Tae Jin Lee, Ji Young Yoo

The Brown Foundation: Institute of Molecular Medicine

FDA-approved oncolytic herpes simplex virus-1 (oHSV) therapy has emerged as a promising viro-immunotherapy for solid tumors. However, tumor- and tumor microenvironment (TME)-associated adaptations following viral treatment, such as feedback immune suppression, neoangiogenesis, and enhanced tumor aggressiveness, often hinder complete tumor eradication. A deeper understanding of the molecular mechanisms underlying resistance to oHSV is crucial to enhancing its clinical impact. We recently discovered that oHSV induces Insulin-like growth factor 2 (IGF2) secretion, shaping an immunosuppressive TME. Similarly, radiotherapy (RTx) activates the IGF1/IGF1R and YAP1 signaling pathways, further promoting therapeutic resistance. In this study, we investigated how oHSV-induced Insulin-like growth factor 1 …

Epilepsy-Associated Digenic Variants Affecting An Actin-Mitochondria-Glutamate Pathway Promote Seizure Susceptibility, Shenzhao Lu, Mengqi Ma, Shabab B Hannan, Mingxi Deng, Hu Chen, Zhijian Yu, Lindsey D Goodman, Haein Kim, Yun Zhao, Sandeep Kumar Dubey, Wen-Wen Lin, Xueyang Pan, Debdeep Dutta, Vishnu Anand Cuddapah, Jill A Rosenfeld, Xi Luo, Zhandong Liu, Joshua M Shulman, Hugo J Bellen

Faculty, Staff and Students Publications

Epilepsy affects approximately 50 million people worldwide, yet more than half of individuals with a presumed genetic cause still lack a molecular diagnosis despite the identification of over 1,000 monogenic epilepsy genes. This diagnostic gap is unlikely to be resolved by improved variant detection alone, suggesting that variants affecting the same biological pathway may combine to cause disease. By studying epilepsy-associated actin regulatory genes, we identified a conserved "actin-mitochondria-glutamate (AMG) pathway". We demonstrate that reduced actin polymerization promotes DRP1-mediated mitochondrial fission, increases reactive oxygen species (ROS) levels, and enhances glutamatergic transmission, leading to seizures. The glial innate immune pathway, a …

Tau Seeds Induce Neurofibrillary Tangle Formation Across Brain Regions Via Individual-Specific Connectivity, Audrey J Weber, Bernard Ng, Kelsey M Greathouse, David A Bennett, Shinya Tasaki, Chris Gaiteri, Jeremy H Herskowitz

Faculty, Staff and Student Publications

The spread of tau pathology across the cerebral cortex is closely tied to cognitive decline in Alzheimer's disease (AD). To investigate mechanisms underlying tau spread, we measured bioactivity of tau seeds from inferior temporal gyrus (ITG) and superior frontal gyrus (SFG) synaptosomes in 128 individuals and demonstrated that tau seed bioactivity associates with tau phosphorylation, neurofibrillary tangles (NFTs), and cognitive impairment. Incorporating genotype data from the same individuals within a Mendelian randomization framework showed that tau seeds in ITG induce NFTs locally as well as drive tau seeds and NFTs in SFG. Integrating antemortem functional magnetic resonance imaging data from …

Impact Of Non-Selective Beta-Blockers On Acute Kidney Injury Outcomes In Patients With Decompensated Cirrhosis, Simone Incicco, Kavish R Patidar, Adrià Juanola, Ann T Ma, Anna Barone, Anand V Kulkarni, José Luis Pérez Hernández, Sumeet K Asrani, Brian Wentworth, Carlo Alessandria, Nadia Abdelaaty Abdelkader, Yu Jun Wong, Qing Xie, Nikolaos T Pyrsopoulos, Sung-Eun Kim, Yasser Fouad, Aldo Torre, Eira Cerda Reyes, Javier Díaz-Ferrer, Rakhi Maiwall, Douglas A Simonetto, Maria Papp, Eric S Orman, Giovanni Perricone, Cristina Solé, Christian M Lange, Alberto Queiroz Farias, Gustavo Pereira, Sebastian Marciano, Paolo Caraceni, Thierry Thévenot, Nipun Verma, Jeong Han Kim, Julio D Vorobioff, Jacqueline Cordova-Gallardo, Vasilisa R Grechishnikova, Raoel Maan, Juan Pablo Roblero, Claudio Toledo, Stefania Gioia, Eduardo Fassio, Mónica Marino, Puria Nabilou, Victor Vargas, Manuela Merli, Luciana Lofego Goncalves, Liane Rabinowich, Aleksander Krag, Lorenz Balcar, Adrian Gadano, Francois Durand, Shiv K Sarin, Pere Ginès, Paolo Angeli, Elsa Solà, Salvatore Piano, International Club Of Ascites Global Aki Team

Faculty, Staff and Students Publications

Background & aims: Non-selective beta-blockers (NSBBs) are widely used to prevent decompensation in cirrhosis. Guidelines recommend discontinuing NSBBs in patients with cirrhosis and acute kidney injury (AKI), although this recommendation is based largely on expert opinion and limited evidence. We evaluated the impact of NSBB use on AKI outcomes in patients with cirrhosis.

Methods: This multicenter study enrolled patients hospitalized for decompensated cirrhosis and AKI. Data on NSBB treatment, including type, dose, and continuation, discontinuation, or tapering, were collected. Outcomes were compared between patients receiving and not receiving NSBBs and between those who discontinued/tapered and those who did not. Inverse …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Strategies To Increase Attendance In Substance Use Disorder Group Treatment: Results From A Randomized Controlled Trial, Liliane Cambraia Windsor, Heather A Jones, Carla Ellis, Kennya Hooper, Andrea Rucker, Salma Musaad, Moses Okumu

Faculty, Staff and Students Publications

Background: Attendance in substance-use-disorder group-treatment is challenging with only 32% of patients attending at least one session (Substance Abuse and Mental Health Services Administration and Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2023 admissions to and discharges from substance use treatment services reported by single state agencies, Bethesda, 2025). The present study tested a set of strategies to increase group session attendance in Community Wise, an innovative evidence-based group-intervention delivered in harm-reduction-community-based agencies and designed to reduce alcohol and substance use among people with substance-use-disorders living in predominantly Black and disinvested communities. We examined: (1) …

Metabolic Syndrome Is Associated With Increased Mortality In Patients With Breast Or Prostate Cancer, Jessica P Hwang, Ning Zhang, Mercy W Misoi, Sabhi Gull, Zayd A Razouki, Justin R Gregg, Natalia I Heredia, Sharon H Giordano

Faculty, Staff and Student Publications

We investigated the association of metabolic syndrome (MetS) with mortality in patients with breast and prostate cancer. Breast and prostate cancer cohorts were created retrospectively using the SEER-Medicare database. Patients with first primary breast or prostate cancer diagnosed in 2008-2019 were identified using ICD-O-3 site and histology codes. Among those, patients with MetS were identified using ICD-9/10-CM codes, CPT/HCPCS codes, and prescription drug use from Medicare claims files. We defined continuous enrollment from 12 months before through 12 months after diagnosis, exposure during the first 12 months after diagnosis, and survival follow-up starting 12 months after diagnosis. We used multivariable …

Subjective Sleep Disruption, Coping, And Anxiety And Related Symptoms In The Perinatal Period: Findings From A Longitudinal Study, Rebecca C Cox, Caroline P Hoyniak, Jack Samuels, Jonathan S Abramowitz, Gerald Nestadt, Eric A Storch, Rashelle Musci, Paul Nestadt, Lauren M Osborne, Mary Kimmel

Faculty, Staff and Students Publications

Study objectives: Anxiety is common during the perinatal period and is associated with adverse maternal and infant outcomes, highlighting a need to identify predictors of perinatal anxiety. Accumulating research implicates sleep disruption in perinatal anxiety and related symptoms, including obsessive-compulsive symptoms. We examined the associations among insomnia symptoms and sleep duration with perinatal anxiety, obsessive beliefs, and obsessive-compulsive symptoms and the moderating role of coping from pregnancy through postpartum.

Methods: A sample of 231 women (agemean = 32.97 ± 4.36 years; 74% white) completed interview and self-report measures of sleep, coping, perinatal anxiety, obsessive beliefs, and obsessive-compulsive symptoms in early …

Unbiased Avidity-Based Isolation Of Antigen-Specific T Cells, Amanda Montoya, Meredith L Frank, Peixin Jiang, Hui Nie, Minying Zhang, Emily Bontekoe, Jared K Slone, Ludovica L Posta, Sofia Rosy Caterina Sorice, Tina Cascone, Maura Gillison, Don L Gibbons, Jianjun Zhang, Eleonora Dondossola, Lydia Kavraki, Pamela L Wenzel, John V Heymach, Alexandre Reuben

The Brown Foundation: Institute of Molecular Medicine

Background: Cancer immunotherapies have significantly improved treatment efficacy and patient survival by exploiting antigen-specific T cells to eliminate cancer cells. However, current approaches for identifying and isolating antigen-specific T cells typically require prior knowledge of target antigens, limiting discovery, and reducing the ability to consistently detect rare tumor-reactive T cells. We therefore sought to develop an unbiased platform for the identification and enrichment of antigen-specific T cells using naturally processed and presented tumor antigens.

Methods: We developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a microfluidic platform that applies controlled shear stress and leverages tumor cells …

Promoting Equity For Children And Adolescents Through Implementation Processes In Health And Social Care: A Scoping Review, Michelle Gooey, Heather Morris, Rebecca Madill, Callie Walsh-Bailey, Ahlia Griffiths, Melissa Savaglio, Claire Blewitt, Amanda O'Connor, Sara Holton, Helia Khalesi, Sofia Grage-Moore, Maria Fernandez, Echezona E Ezeanolue, Allison Metz, Ana Baumann, Helen Skouteris

Faculty, Staff and Student Publications

Background: Despite the many existing implementation methods, theories, and frameworks, implementation science is insufficiently closing the research-to-practice gap. Bridging this gap is critical to achieving healthy and thriving communities globally, and requires implementation processes that promote equity and reach diverse populations, especially those most in need. The aim of this scoping review was to identify, thematically analyse, categorise, and provide examples of implementation processes described in equity-focused literature, with a focus on health and social care interventions for children and adolescents from birth to 18 years of age.

Methods: A comprehensive search of literature was undertaken across six electronic databases …

Thanks For The Signal-Now What? Program Director Perspectives On How Preference Signals Are Shaping General Surgery Residency Recruitment, John M Woodward, Connie Y Gan, Darci C Foote, Tasha Posid, Nicole M Santucci, Noosha D Deravi, Caitlin Silvestri, Kirstyn E Brownson, Erika Simmerman Mabes, Rondi Gelbard, Milanie Milan, Nina Zhao, Dylan R Nieman, Martha Godfrey, Benjamin D Ferguson, Joseph C L'Huillier, Colleen Mcdermott, Prajjwol Luitel, Olabisi Sheppard, Jennifer H Chen, Emma G Burke, Jenny M Guido, Ladonna Kearse, Jonathan Davies, Trenton Foster, Sarah Lund

Faculty, Staff and Students Publications

Objective: We aimed to explore general surgery program director (PD) experiences with and perspectives on preference signaling in a 15-signal system.

Design: We performed qualitative analysis of de-identified transcripts from semi-structured interviews of general surgery PDs.

Setting: General surgery PDs across the United States.

Participants: All general surgery PDs in the spring of 2025 were invited to participate. Fifteen PDs volunteered to participate in semi-structured interviews (73% university-based, 53% programs with < 8 residents/class).

Results: PDs highlighted that signals saved time when utilized as a screening tool, which gave PDs more time for holistic review of applications. PDs also felt signaling increased equity …

Association Between Author Specialty And Reported Outcomes In Non-Randomized Comparisons Of Prostatectomy Versus Radiation, Zakaria El Kouzi, Mohammed A Mohammed, Michael Kevin Rooney, Ramez Kouzy, Jie Jane Chen, Shalin Shah, Tarek Al Bitar, Sherif M Gadoue, Comron Hassanzadeh, Steven Frank, Phuoc Tho Tran, Chad Tang, Seungtaek Choi, Ryan Jin-Hyung Park, Karen Hoffman, Sean Eric Mcguire, Henry Mok, Quynh-Nhu Nguyen, Adam B Samman, Zain Rahman, Mohamed Shelan, Toufic Eid, Osama Mohamad

Faculty, Staff and Students Publications

Background: While the ProtecT randomized trial demonstrated comparable oncologic outcomes between radical prostatectomy (RP) and radiation therapy (RT) for localized prostate cancer, several retrospective studies have reported mixed findings. In this study, we investigated whether non-randomized studies tend to favor RP or RT and assessed whether the specialty of leading authors-urologists or radiation oncologists-correlates with study conclusions.

Methods: We identified non-randomized clinical studies published between 1993 and 2024 that compared RP and RT for localized prostate cancer and reported oncologic outcomes including biochemical, metastasis, and/or survival outcomes. Author specialty was determined based on whether the first and senior authors were …

Aberrant Ciliogenesis Induced By Enhanced Bmp Signaling Causes Heterotopic Ossification, Hiroyuki Yamaguchi, Jianbo Wang, Fangfang Yan, Jiarui Bi, Radbod Darabi, William R. Lagor, Zhongming Zhao, Aris N. Economides, Yuji Mishina, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Bone morphogenetic protein (BMP) signaling is a principal driver of heterotopic ossification (HO), yet how aberrant BMP activity structurally reprograms cellular signaling machinery to develop HO remains unclear. Here, we identify BMP signaling as a direct upstream regulator of ciliogenesis that coordinates a multi-stage, pro-osteochondrogenic signaling relay during HO. Using a conditional gain-of-function BMP mouse model (Acvr1Q207D/+), we demonstrate that enhanced BMP signaling promotes primary cilium biogenesis and axonemal elongation through canonical Smad1/5/9-dependent transcriptional activation of intraflagellar transport (IFT) Ift20, a core component of the IFT machinery. Rather than operating via a singular downstream cascade, these elongated …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

Clinical Document Metadata Extraction: A Scoping Review, Kurt Miller, Qiuhao Lu, William Hersh, Kirk Roberts, Steven Bedrick, Andrew Wen, Hongfang Liu

Faculty, Staff and Student Publications

Objectives: Clinical document metadata, such as document type, structure, author role, medical specialty, and encounter setting, is essential for accurate interpretation of information captured in clinical documents. However, vast documentation heterogeneity and drift over time challenge harmonization of document metadata. Automated extraction methods have emerged to coalesce metadata from disparate practices into target schema. This scoping review aims to catalog research on clinical document metadata extraction, identify methodological trends and applications, and highlight gaps warranting further investigation.

Methods: We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to identify articles from Ovid …

Implementation And Evaluation Of The Owll Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Mixed-Methods Approach, Kawtar Zouaidi, Jan Yeager, Sayali Tungare, Suhasini Bangar, Janelle Urata, Alfa-Ibrahim Yansane, Jungsoo Kim, Emily Sedlock, Krishna K Kookal, Yan Xiao, Oluwabunmi Tokede, Heiko Spallek, Amy Franklin, Gregory Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: The OWLL (Open-Wide Learning Lab) intervention was developed using Human-Centered Design to improve the quality and safety of pediatric dental sedation. The intervention includes a patient-facing informational sedation brochure and video, and an enhanced set of clinical sedation records. Here, we report on the process evaluation 6 months after implementation in daily clinical practice.

Methods: This study was conducted at the outpatient pediatric dental clinics of 2 large US academic dental institutions. We used a mixed-methods design to assess the fidelity, acceptability, appropriateness, and feasibility of the OWLL intervention. Quantitative data were gathered through chart reviews, while qualitative data …

Mapping Dna Methylation Signatures To Identify Epigenetic Variation Across Subcortical Regions Of The Human Posttraumatic Stress Disorder Brain, Hongyu Li, Yujing Liu, Yiming Shi, Jiawei Wang, Tuan P Nguyen, Yuhan Xie, Wangjie Zheng, Youshu Cheng, Dianne A Cruz, Jennifer L Modliszewski, Rosemarie Terwilliger, Alexa-Nicole Sliby, José Jaime Martínez-Magaña, Janitza L Montalvo-Ortiz, John D Roache, Lynnette A Averill, Stacey Young-Mccaughan, Paulo R Shiroma, Bertrand R Huber, David A Lewis, Jill Glausier, Paul Holtzheimer, Matthew J Friedman, Jing Zhang, Alan L Peterson, Chadi G Abdallah, Amir Valizadeh, Xinyu Zhang, Ke Xu, John H Krystal, Ronald S Duman, Hongyu Zhao, David L Corcoran, Douglas E Williamson, Matthew J Girgenti

Staff and Researcher Publications

Background: Posttraumatic stress disorder (PTSD) is a mental disorder that may occur in the aftermath of severe psychological trauma. Epigenetic changes in the brain may play a critical role in understanding the neurobiology of PTSD by linking environmental traumatic stress exposure to lasting alterations in gene expression that shape neuronal function.

Methods: We examined 1,065,750 DNA methylation (DNAm) sites from 171 donors including neurotypical controls and PTSD and major depressive disorder (MDD) cases across 6 regions implicated in the fear circuitry of the brain. We performed RNA sequencing (RNA-seq) to examine changes in gene expression and linked these changes to …

Antibiotic Administration After Previable Preterm Prelabor Rupture Of Membranes Is Associated With Prolonged Latency, Alexandra L Hammerquist, Alexander M Saucedo, Selina L Bowler, Mohan Pammi, Catherine Eppes, Ignatia Van Den Veyver, Michael D Jochum, Enrico R Barrozo

Duncan NRI Faculty and Staff Publications

Introduction: While antibiotics have been shown to increase the interval to delivery between rupture of membranes and delivery (latency) and improve neonatal outcomes after viable preterm prelabor rupture of membranes (PPROM), this has not been well investigated in the previable PPROM population. We aimed to investigate the association between antenatal antibiotics and latency following previable PPROM. Secondarily, we examined various maternal and neonatal outcomes. We hypothesized that the administration of antibiotics would prolong latency in pregnancies with previable PPROM.

Methods: Single-center retrospective cohort study that included pregnancies diagnosed with previable PPROM between 140/7 and 216/7 and delivered between 2012 and …

Patient Perspectives On Psychiatric Polygenic Risk Scores In Reproductive Decision-Making And Polygenic Embryo Screening., Lauren A Ginn, Amanda R Merner, Page M Trotter, Kaitlynn P Craig, Abigail C Martinez, Ana Lucía Battaglino, Dorit Barlevy, Daphne M Ayton, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Polygenic risk scores (PRS) estimate individuals' genetic risk for developing multifactorial conditions. Recent genome-wide association studies have enabled development of psychiatric PRS, which hold potential to streamline diagnosis and treatment of psychiatric conditions. As individuals with mental illness often identify concern about passing on psychiatric conditions as a key factor in family planning, some may also seek to use psychiatric PRS in reproductive decisions like childbearing or embryo selection for in vitro fertilization. Despite calls for increased regulation, there remains no clinical consensus on the utility of psychiatric PRS in reproductive contexts. Therefore, we conducted semi-structured interviews of adults with …

An Integrated Cardiometabolic Genetic Testing Program In A Predominantly Hispanic Population Within A Community Setting, Bo Yuan, Layla A Abushamat, Stacey Pereira, Surya Narayan Mulukutla, Grace E Tietz, Eric Venner, Sara E Kalla, Breanna Lee, Donna Muzny, Ginger Metcalf, Mullai Murugan, Sarah H Elsea, Senkottuvelan Kadirvel, Lele Li, Joshi Stephen, Shengfeng Xu, Victoria Yi, Monica Sulit, Christie L Kovar, Kimberly Walker, Marie-Claude Gingras, Jianhong Hu, Fei Yan, Taeko Gerber, Viktoriya Korchina, C Michael Fordis, Ruchi Gaba, Mahesh Changlani, Herschl Silberman, Hadley Stevens Smith, Christine M Eng, Jennifer E Posey, Clarisa Medina, Lisa R Treviño, Christie M Ballantyne, Richard A Gibbs, Ashok Balasubramanyam

Center for Medical Ethics and Health Policy Staff Publications

Purpose: This study aimed to apply cardiometabolic genetic testing in a community setting with a predominantly Hispanic population and assess feasibility and perspectives toward genetic testing.

Methods: A genome-sequencing-based genetic panel for cardiometabolic disorders (177 genes related to monogenic conditions, 2 LPA risk alleles, 2 pharmacogenomic loci, and ancestry-adjusted polygenic risk scores for type 2 diabetes and coronary artery disease) was deployed in community cardiology and endocrinology clinics in South Texas. A survey on perceptions toward genetic testing was administered after return of results.

Results: Testing was completed for 776 patients (18-92 years old, 92% Hispanic). 26 patients (3.4%) were …

Zeb1 Modifies Ve-Cadherin Signaling In Lymphatic Endothelial Cells, Nada S Ahmed, Joseph L Horder, Charles T Cresswell, Poppy E Harris, Amy P Lynch, Zarah B Tabrizi, Kathryn R Green, James H Hallwood, Anton C Smith, Michael A Portelli, Alexander J Fezovich, Christos Spanos, David S Gardner, Alan Mcintyre, Sarah J Storr, Daniel G Booth, David O Bates, Andrew V Benest

Faculty, Staff and Students Publications

Objective: Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor primarily known for its regulatory roles in epithelial-to-mesenchymal transition (EMT) and cell fate determination. Recent studies suggest that endothelial ZEB1 signaling promotes blood vessel growth and reduces junctional integrity, although the underlying mechanisms remain unclear. Notably, the role of ZEB1 in the lymphatic vasculature is unknown, and the regulation of lymphatic integrity by VE-cadherin remains poorly defined.

Methods: Here, using an integrated proteomic and transcriptomic approach, we identify ZEB1-dependent signaling pathways associated with cell-cell junction reorganization in lymphatic endothelial cells (LECs).

Results: Loss of ZEB1 reduced VE-cadherin phosphorylation at …

Autoimmune Disease Risk With Glp-1ra, Dpp-4i, And Sglt2i Treatment In Patients With Diabetes, Arjun Mahajan, David W Bates, Alessandro Doria, Dinah Foer, Avery H Lachance, Jeffrey A Sparks

Faculty, Staff and Students Publications

Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used for type 2 diabetes, yet their comparative immunologic safety is uncertain. To address this gap, we evaluated autoimmune disease incidence among patients treated with these agents.

Methods: We conducted emulated target trials using electronic health record data from 152 health care organizations in the TriNetX network (2016-2023). Adults with type 2 diabetes initiating DPP-4i, GLP-1RA, or SGLT2i monotherapy and no prior autoimmune disease were included. Propensity score matching balanced demographics, comorbidities, laboratory data, and medications. Cohorts comprised 118,419 matched DPP-4i versus GLP-1RA …

Performance Of Fecal Calprotectin And Serum Procalcitonin For The Diagnosis Of Spontaneous Bacterial Peritonitis In Patients With Cirrhosis: A Prospective Diagnostic Accuracy Study, Mandip Singh Bhatia, Devarakonda Uday Teja, Nipun Verma, Archana Angrup, Saurabh Chandrabhan Sharda

Faculty, Staff and Students Publications

Background:: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis and ascites. This study aimed to evaluate the diagnostic performance of biomarkers—calprotectin (serum, ascitic, fecal) and serum procalcitonin (PCT)—for SBP.

Methods:: This prospective diagnostic accuracy study, enrolled 137 consecutive patients with cirrhosis and ascites at a tertiary care center in India. Participants were categorized into SBP (n = 55) and non-SBP (n = 82) groups based on the reference standard of ascitic fluid neutrophil count. Serum, ascitic fluid, and fecal calprotectin were measured by enzyme-linked immunosorbent assay, and serum PCT was measured by electrochemiluminescence immunoassay. …

Development And Validation Of The A-Tango Organ Failure Score For Acute-On-Chronic Liver Failure In Global Cohorts, Cornelius Engelmann, Nipun Verma, Tingting Qi, Annarein Johanna Catharina Kerbert, Julian Pohl, Carrie Morgan, Michal Kowalski, Fausto Andreola, Marcelo Oscar Silva, Jose Luis Perez Hernandez, Renato Palma-Fernandez, Manuel Mendizabal, Osvely Mendez-Guerrero, Jose Luis Marin, Sebastián Marciano, René Male-Velazquez, Maria Sarai González-Huezo, Adrian Gadano, Fernando Bessone, Carlos Benitez, Oscar Alfredo Beltran Galvis, Mauricio Castillo Barradas, Marco Arrese, Karen Vagner-Danielsen, Peter Jarcuska, Boglarka Balogh, Zsuzsanna Vitalis, Antonella Putignano, Manuel Tufoni, Michael Manns, Claire Francoz, Manuel Romero-Gomez, Stephen Ryder, Pierre Nahon, Sven Francque, Osman Özdogan, Cristina Sole, Jose Presa Ramos, Heinz Zoller, Manuela Merli, Flemming Bendtsen, Thomas Berg, Alexander Zipprich, Pietro Gatti, Juan Acevedo, Martin Janicko, Frank Erhard Uschner, Carmine Gabriele Gambino, Giacomo Zaccherini, Xianbo Wang, Xin Zheng, Guohong Deng, Yan Huang, Zhongji Meng, Yanghang Gao, Zhiping Qian, Xiaobo Lu, Feng Lui, Yu Shi, Jia Shang, Yubao Zheng, Yingli He, Sunil Taneja, Pratibha Garg, Hans Van Vlierberghe, Christian Steib, Rudolf Stauber, German Soriano, Raj Mookerjee, Henning Gronbaek, Andrea De Gottardi, Minneke Coenraad, Rafael Banares, Stefan Zeuzem, Alexander Gerbes, Marco Domenicali, Faouzi Saliba, Francois Durand, Hai Li, Ajay Duseja, Jinjun Chen, Rajiv Jalan

Faculty, Staff and Students Publications

Background & aims: Acute-on-chronic liver failure (ACLF) is characterised by multiorgan failure and high short-term mortality in hospitalised patients with acute decompensation of cirrhosis. Although the EASL-CLIF criteria are widely used for diagnosis and prognostication, evolving definitions of organ dysfunction and emerging therapies require updated, tailored criteria to improve diagnostic accuracy, treatment assessment, and applicability in clinical trials. We aimed to develop and validate the A-TANGO organ failure (OF) score to refine ACLF diagnosis and enhance its utility for treatment response evaluation and risk stratification.

Methods: We performed a retrospective analysis of prospective observational cohorts. The derivation cohort comprised three …