Digital Commons Network^™

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 …

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 …

Sex Differences In The Protective Effect Of Brain Volume: Age Attenuates Protection In Women, Javier Gomez-Farias, Ngoc Mai Le, Joseph N Samaha, Bruna Kfoury, Hussain M Azeem, Ritesh Bajaj, Mahnoor Khalid, Freya Kanakhara, Shikha Tripathi, Shayan Shams, Luca Giancardo, Eunyoung A Lee, Robert W Regenhardt, Louise D Mccullough, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Sex differences in outcomes after acute ischemic stroke are well recognized, but mechanisms remain unclear. This study evaluates whether parenchymal brain volume (PBV), age, and final infarct volume explain sex-specific differences in poststroke disability.

Methods: We analyzed a prospectively collected multicenter registry of acute ischemic stroke patients treated between 2015 and 2024. Automated pipelines quantified PBV from noncontrast computed tomography and diffusion-weighted imaging-derived final infarct volume from 24- to 48-hour magnetic resonance imaging. With the primary outcome being 90-day functional independence (modified Rankin Scale score 0-2), sex-stratified logistic regression models evaluated its association with PBV. Stratified logistic and linear …

Medadl: High-Throughput Information Extraction Of Functional Status From Electronic Health Records To Advance Frailty Assessment In Older Adults, Sunyang Fu, Zhiyi Yue, Jennyly T Nguyen, Huipeng Liu, Jaerong Ahn, Vanessa Ramirez, Jude Des Bordes, Hongfang Liu, Min Ji Kwak, Nahid J Rianon

Faculty, Staff and Student Publications

Background: Functional status is essential for assessing frailty and planning care in older adults but is often under-documented in the structured fields of electronic health records. Manual chart review can capture functional status information but is labor-intensive and time-consuming. In this study, we developed and validated a scalable natural language processing (NLP) model to extract functional status information from unstructured electronic health record (EHR) notes.

Methods: This retrospective cohort study included 110 older adults seen at a geriatric osteoporosis clinic. A large language model-augmented symbolic NLP pipeline (MedADL) was developed to extract activities of daily living (ADL) and instrumental activities …

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 …

Neighbourhood Social Vulnerability And Preterm Birth Risk Among Infants With Trisomy 21: A Statewide Analysis, Fatima R Sheriff, Renata H Benjamin, Qian Xiao, Jenil Patel, Charles Shumate, Alejandra Fernandez, A J Agopian

Faculty, Staff and Student Publications

Background: Residing in socioeconomically vulnerable areas is known to be associated with increased preterm birth (PTB) risk in the general population. However, the relationship between social vulnerability and PTB remains unexplored among infants with trisomy 21, who experience more than twice the PTB rate of the general population.

Objectives: The primary objective was to examine the association between maternal socioeconomic vulnerability, as measured by the SVI, and PTB among infants with trisomy 21.

Methods: We conducted a retrospective cohort study among infants with trisomy 21 born in Texas (1999-2018). We examined the association between neighbourhood vulnerability, measured by Social Vulnerability …

Cost Utility Analysis Of Fluticasone Exhalation Delivery System Versus Budesonide Nasal Irrigation For Chronic Rhinosinusitis With Nasal Polyps, Daniel Xiao, Martin J Citardi, William C Yao, Amber U Luong

The Brown Foundation: Institute of Molecular Medicine

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is managed after sinus surgery with topical corticosteroids. Given limited distribution of nasal steroid sprays, patients have the option of either steroid nasal irrigation (SNI) or exhalation delivery system with fluticasone (EDS-FLU). This study evaluates the cost-effectiveness of EDS-FLU compared to SNI for CRSwNP.

Methods: A cohort-style Markov decision-tree economic model with a 33-year time horizon was developed in TreeAgePro. Because EDS-FLU is not currently covered by Medicare, costs of medications were estimated using retail pricing. A willingness-to-pay threshold of $50,000/quality adjusted life year (QALY) was used to determine cost-effectiveness. One-way and probabilistic …

Functional Characterization Of Uhrf1 Variants In Facilitating Dna Methylation, Bigang Liu, Kaila Nayvelt, Swanand Hardikar, Kimie Kondo, Marcos R Estecio, Xiaodong Cheng, Taiping Chen

The Brown Foundation: Institute of Molecular Medicine

Ubiquitin-like with plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) is essential for DNA methylation inheritance. However, the functional impacts of several natural and engineered UHRF1 variants are either insufficiently characterized or obscured by conflicting results, with some discrepancies likely stemming from cellular toxicity and adaptive responses induced by DNA methylation changes. In this study, we utilized mouse embryonic stem cells (mESCs)-which uniquely tolerate the complete loss of DNA methylation-to evaluate the functional consequences of clinical mutations, isoform variation, and epitope tagging. Using rescue experiments in Uhrf1-deficient mESCs, we characterized two UHRF1 mutations identified in …

Mosaic Loss Of Y Chromosome Associates With Lung Function, Emphysema, And Epigenetic Aging, Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle, R Graham Barr, Stephen S Rich, Jerome I Rotter, April P Carson, Laura M Raffield, Sina A Gharib, Traci M Bartz, Bruce M Psaty, Tamar Sofer, Kari E North, Robert C Kaplan, Elizabeth C Oelsner, Ani Manichaikul, Alexander G Bick, Paul Scheet, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine Consortium, Yasminka A Jakubek, Paul L Auer, Michael H Cho, Dawn L Demeo

Faculty, Staff and Student Publications

Rationale: As the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.

Objectives: To examine the association between mLOY and pulmonary outcomes in men.

Methods: Leveraging mLOY assessment (cell fraction ≥ 5%) in over 12 000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, …

Current Adoption Of The Prosthodontic Diagnostic Index For Clinical Care-A Cross-Sectional Survey Study, Esther O Kuyinu, Joseph B Breitman, Arthur Nimmo, Jay S Patel

Faculty, Staff and Student Publications

Purpose: To assess current utilization of the Prosthodontic Diagnostic Index (PDI), identify perceived benefits and limitations, and evaluate support for future updates.

Materials and methods: A survey regarding the use of the PDI was made available through email invitations to 68 US dental school prosthodontic/restorative department chairs (PD), 48 graduate prosthodontic program directors (GP), and 1834 private practice prosthodontists (PP) from the American College of Prosthodontists (ACP) member database. The results of this initial survey were inconclusive due to low response rates. The survey was also administered during the 2024 ACP Annual Session with an improved response rate for educators. …

Kras G12c And Kras G12d Respond To Lipid Metabolism In An Allele-Specific Manner, Neha Arora, Hong Liang, Walaa Kattan, Wantong Yao, Haoqiang Ying, Junchen Liu, Yong Zhou

Faculty, Staff and Student Publications

KRAS mutated at hotspots G12, G13, and Q61 possess profound allele-specific oncogenesis. Signaling of KRAS mutants is mostly compartmentalized to the proteolipid nanoclusters on the plasma membrane (PM), illustrating critical roles of spatiotemporal organization in KRAS cancer signaling. The activated GTP-bound KRAS molecules, including the wild type and mutants, have been traditionally thought to favor similar lipids. We recently reported distinct lipid sensing capabilities of different KRAS mutants, especially with KRASG12D favoring unsaturated lipids and KRASG12C gaining additional enrichment of saturated lipids. As such, KRAS mutants may respond to lipid acyl chain remodeling in an allele-specific manner. Lysophosphatidylcholine acyltransferase 1 …

Quantitative Analysis Of Peri-Implant Collagen Fiber Orientation Around External Hexagon And Morse Taper Implant Connections: A Dog Model Study, Daniel Sartorelli Marques De Castro, Jefferson David Melo De Matos, Jozely Francisca Mello Lima, Maria Angelica Rehder De Araujo, Mário Alexandre Coelho Sinhoreti, Daher Antonio Queiroz, Adriano Piattelli, Carlos Dos Reis Pereira De Araújo

Faculty, Staff and Student Publications

Background: Peri-implant soft tissue stability depends on the implant-abutment interface and collagen fiber organization. Unlike natural teeth, peri-implant fibers exhibit a less favorable orientation, potentially weakening the biological seal. Implant connection design may influence this collagen arrangement and tissue integrity.

Materials and methods: Eighteen immediately loaded implants (n = 9 per group) were placed in nine mongrel dogs. Group I received external hexagon implants, while Group II received Morse taper implants. After a 4-month healing period, animals were euthanized and specimens were processed for histological evaluation. Collagen fiber orientation was analyzed using polarized light microscopy and quantified with ImageJ software. …