Digital Commons Network^™

Evaluating The Utility Of Rnaseq In Prenatal Diagnostics: Expression Profiles Of Cultured Chorionic Villus And Amniotic Fluid Samples, Maria C Vladoiu, Sen Zhao, Roni Zemet, Christian M Parobek, Jefferson Cruz Sinson, Stacy Tankersley, Ignatia B Van Den Veyver, Pengfei Liu

Duncan NRI Faculty and Staff Publications

Objective: While RNAseq has enhanced variant interpretation in postnatal cases, its potential in the prenatal setting remains underexplored. This study investigates the utility of RNAseq in prenatal diagnostics by analyzing the expression profiles of cultured chorionic villus samples (cCVS) and amniotic fluid (cAF) samples.

Methods: We performed RNAseq on 25 prenatal samples (10 cCVS and 15 cAF) and compared their expression profiles with those of postnatal tissues-blood and skin fibroblasts.

Results: To evaluate the clinical relevance of gene expression in these samples, we curated a list of genes associated with fetal-onset genetic disorders (n = 375). Using this curated list …

Evapecognition: An 18-Year Dataset Of Great Ape Cognition, Alejandro Sánchez-Amaro, Sonja J Ebel Van Wijk, Carin Molenaar, Akzira Abuova, Lizbeth Mujica-Manrique, Sarah M Leisterer-Peoples, Bret Beheim, Luke Maurits, Anna Albiach-Serrano, Matthias Allritz, Nazli Altınok, Federica Amici, Alice Mi Auersperg, Filippo Aureli, Elisa Bandini, Jochen Barth, Leïla Benziad, Bettina E Bläsing, Manuel Bohn, Marie Bourjade, Juliane Bräuer, Marie-Hélène Broihanne, Sarah F Brosnan, Nereida Bueno-Guerra, Thomas Bugnyar, David Buttelmann, Frances Buttelmann, Trix Cacchione, Malinda Carpenter, Fernando Colmenares, Catherine Crockford, Katherine A Cronin, África De Las Heras, Arianna De Marco, Sarah E Detroy, Valérie Dufour, Shona Duguid, Robin I M Dunbar, Johanna Eckert, Jan M Engelmann, Joel Fagot, Julia Fischer, Sofia Ingrid Fredrika Forss, Martina Funk, György Gergely, Julia R Greenberg, Johannes Großmann, Sebastian Grüneisen, Marta Halina, Daniel Hanus, Sarah R Heilbronner, Christophe Heintz, Robert Hepach, Esther Herrmann, Satoshi Hirata, Alenka Hribar, Gabriele Janzen, Juliane Kaminski, Patricia Kanngiesser, Fumihiro Kano, Katharina C Kirchhofer, Hagen Knofe, Kathrin S Kopp, Christopher Krupenye, Isabelle Barbara Laumer, Stephen C Levinson, Ulf Liszkowski, Héctor M Manrique, Gema Martin-Ordas, Emma Suvi Mcewen, Richard T Moore, Enric Munar, Marcos Nadal, Christian Nawroth, Suska Nolte, Marie Pelé, Patrizia Potì, Hannes Rakoczy, Julia Riedel, Amélie Romain, Federico Rossano, Yvan I Russell, Gloria Sabbatini, Marie Schäfer, Marina Scheumann, Martin Schmelz, Benjamin Schmid, Vanesa Schmitt, Carla Sebastián-Enesco, Amanda Madeleine Seed, Chikako Suda-King, Tibor Tauzin, Sebastian Tempelmann, Claudio Tennie, Valentina Truppa, Jana Uher, Amrisha Vaish, Edwin J C Van Leeuwen, Elisabetta M Visalberghi, Christoph J Völter, Victoria Vonau, Claudia A F Wascher, Roman M Wittig, Wouter Wolf, Michael Tomasello, Katja Liebal, Josep Call, Daniel B M Haun

Faculty, Staff and Students Publications

The study of great ape cognition offers insights into the evolutionary origins of human intelligence, but is hindered by small sample sizes and restricted access to data. To address this, we present the EVApeCognition Dataset, a publicly available resource comprising 262 experimental datasets from 150 scientific publications from the Wolfgang Köhler Primate Research Center (2004-2021) in Leipzig, Germany. Eighty-one apes participated in 150 studies, with a majority (N = 78) participating in more than one study. Publication of the dataset aims to make these unique datasets accessible for future meta-analyses and correlational analyses, helping us better understand how our great …

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). …

The Effects Of Orexin Receptor Antagonism During Early Withdrawal In Stimulant Use Disorder: Protocol For A Proof-Of-Concept Study, Heather Webber, Nikky Tran, Rita Blake, Sarah Goldman, Trevor George, Bill Bailey, Robert Suchting, Jin Yoon, Jessica Vincent, Michael Weaver, Joy Schmitz, Scott Lane

Faculty, Staff and Student Publications

Background: Stimulant use disorders (StimUDs), including cocaine and methamphetamine use disorders, remain a major public health concern in the United States with no US Food and Drug Administration (FDA)-approved pharmacological treatments. The early recovery period following stimulant use is marked by sleep disturbances, heightened stress reactivity, and dysregulated reward processing, contributing to high rates of resumption of use. Evidence from animal and human studies supports the orexin neuropeptide system as a promising therapeutic target for minimizing these disruptive mechanisms. Suvorexant, an FDA-approved dual orexin receptor antagonist for insomnia, has previously been shown to improve sleep, reduce stress, and attenuate craving …

Integration Of Aged Brain Multi-Omics Reveals Cross-System Mechanisms Underlying Alzheimer’S Disease Heterogeneity, Lucas P Scheidemantel, Katia De Paiva Lopes, Chris Gaiteri, Vilas Menon, Philip L De Jager, Julie A Schneider, Aron S Buchman, Yanling Wang, Shinya Tasaki, Roberto T Raittz, David A Bennett, Ricardo A Vialle

Faculty, Staff and Student Publications

The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is characterized by elevated immune activity at the epigenetic level, decreased heat shock gene expression in the transcriptome, and disrupted energy metabolism and cytoskeletal dynamics in the proteome. Unsupervised clustering …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Relative Impact Of Multidomain Lifestyle Interventions On Deficit Accumulation Frailty Over 24 Months In The U.S. Pointer Trial, Mark A Espeland, Kayloni Olson, Christy C Tangney, Darren R Gitelman, Maryjo Cleveland, Amber A Thro, Yitbarek N Demesie, Heather M Snyder, Rachel A Whitmer, Pankaja Desai, Rifat Alam, Lucia Crivelli, Thomas M Holland, Olivia Preissle, Rema Raman, Michele K York, Laura D Baker

Faculty, Staff and Students Publications

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability …

Developing Endpoints For The Cardiac Burden In Myotonic Dystrophy Type 1: A Workshop Report, Julia M Hartman, Samuel Carrell, William J Groh, Thomas A Cooper, Jordana Kron, Greg Hundley, Jennifer Jordan, Amy Ladd, Man Hung, Nicholas E Johnson

Faculty, Staff and Students Publications

Cardiac disease is a well-established manifestation of myotonic dystrophy type 1 (DM1), characterized by progressive cardiac conduction slowing with increased risk of atrial and ventricular arrhythmias, heart block, and sudden cardiac death. Multiple disease modifying therapies are in clinical trials for DM1 and show promise in improving skeletal muscle weakness and myotonia. Testing the effects of these medicines, or others, in the heart is of critical importance, but requires identification of endpoints of cardiac function that accurately reflect the state of DM1 cardiac disease. To better define cardiac endpoints, the Myotonic Dystrophy Clinical Research Network (DMCRN) and the Myotonic Dystrophy …

Structure-Preserving Multivariate Hypothesis Testing For Mass Spectrometry Imaging And Single-Cell Data, Keziah E Liebenberg, Erin Craig, Robert Tibshirani, Livia S Eberlin

Faculty, Staff and Students Publications

Motivation: Mass spectrometry imaging (MSI) and single-cell RNA sequencing (scRNA-seq) offer high-resolution views into tissue and cellular heterogeneity. However, conventional statistical analyses often treat sub-measurements (pixels or cells) as independent, ignoring their nested origin from individual samples. This assumption inflates the effective sample size, increases false discoveries, and undermines biological interpretation. Pixel- or cell-level averaging avoids this but sacrifices spatial or cellular resolution.

Results: We evaluated block-SAM on both simulated and real-world datasets. In DESI-MSI data from kidney, lung, and ovarian tumors, block-SAM consistently identified fewer-but more reliable-differential features compared to traditional-SAM. For example, in the kidney dataset, traditional-SAM identified …

Lgr5: From Stem Cell Marker To Therapeutic Target, Peyton C High, Maya G Cappellino, Tiffani A Blackburn, Kendra S Carmon

Faculty, Staff and Student Publications

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is an established marker of normal and cancer stemlike cells. LGR5 has been implicated in promoting cancer cell plasticity that drives tumorigenesis, metastasis, and therapeutic resistance. LGR5 rapidly and constitutively internalizes and potentiates Wnt (Wingless/Int-1)/β-catenin and adhesion signaling pathways, though its precise mechanisms and interacting partners remain unresolved. An improved understanding of LGR5 signaling may provide invaluable insight into its intricate and important functions in cancer progression. Moreover, several LGR5-targeting therapies, including peptibody- and antibody-drug conjugates and bispecific antibodies, are showing promising efficacy and tolerability in colorectal cancer and other tumor types. This …

A Qualitative Analysis Of Pediatricians' Perspectives Regarding Barriers, Facilitators, And Strategies For Providing Timely Autism Spectrum Disorder Screening And Diagnosis, Mallika Mathur, Jinni Tang, Christine Markham, Sandra Mckay, Ruosha Li, Deepali Ernest, Allison Marshall, Shreela Sharma

Faculty, Staff and Student Publications

Background: Autism spectrum disorder (ASD) is a developmental disorder that has increased in prevalence over the years. Diagnosis and subsequent intervention by the age of 3 is essential for development. However, recent estimates indicate that less than 50% of children receive an evaluation by age 3. Underserved populations are more likely to receive an evaluation at an older age. Several barriers in the diagnostic process have been identified; however, limited studies have aimed at understanding the specifics of these barriers among underserved populations and whether current strategies are beneficial for all children.

Objectives: The aim of this study was to …

Untangling Impacts Of Socioeconomic Position, Chronic Disease, And Low-Level Pm2.5 Exposure On Mortality Among Native American Medicare Beneficiaries, Judy Wendt Hess, Wenyaw Chan

Faculty, Staff and Student Publications

Ambient fine particulate matter (PM2.5) is associated with increased mortality at concentrations below current regulatory standards. Studies of low-level exposure often rely on large administrative cohorts whose geographic and demographic composition may influence observed associations. In a prior analysis, we observed an association between long-term PM2.5 and all-cause mortality among Native American Medicare beneficiaries living in zip codes within the lowest decile of PM2.5 exposure. The present study, a case-control analysis of 1,713,399 low-PM2.5-exposed beneficiaries enrolled in traditional Medicare during 2015-2016, evaluated whether this association could be explained by geographic context, socioeconomic position (SEP), or baseline health status. We used …

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 …

Translationally-Relevant Tumor Resection Model For Murine Preclinical Models Of Oral Squamous Cell Carcinoma, Gemalene M Sunga, Alejandra Cobos Perez, Andrea H Molina, Nourhan Hussein, Neeraja Dharmaraj, Andrew Sikora, Simon Young

Faculty, Staff and Student Publications

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy. However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to …

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 …

Bdcd: A Comprehensive Brain Disease Cell-Cell Communication Database, Xinyi Liu, Citu Citu, Wendao Liu, Nitesh Enduru, Andi Liu, Chia-Hao Tung, Zhongming Zhao

Faculty, Staff and Student Publications

Dysregulated cell–cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, …

Exploring The Ethical And Practical Considerations Of Artificial Intelligence In Real-World Health Care Settings: Stakeholder Focus Group Study, Carmen Wendy Ulizio, Devika Dua, Naya Meenkashi Mukul, Santosh Areti, Kristin Kostick-Quenet, Vasiliki Nataly Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Background: Artificial intelligence (AI) technologies continue to transform how we research human disease, diagnose and treat patients, and operate hospitals. However, emerging ethical dilemmas surrounding their design, use, and oversight demand both policy attention and empirical research.

Objective: This study aims to explore current AI development, integration, and use activities across the Texas Medical Center (TMC), the largest medical center in the world, and identify emerging ethical priorities.

Methods: We conducted a total of 3 qualitative focus groups via Zoom (Zoom Video Communications, Inc) between May and June 2025 to gauge the perspectives of 19 clinicians, developers, administrators, and patient …

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 …

What Is New In Temporary Mechanical Circulatory Support In 2024-2025?, Maya Guglin

The VAD Journal

This review covers the most interesting publications on temporary mechanical circulatory support in 2024-2025. We include the latest research on intra-aortic balloon pumps, Impella devices, and veno-arterial extracorporeal membrane oxygenation.

Comparative Effectiveness Of Radiofrequency Or Microwave Ablation And Chemotherapy For The Treatment Of Large (>5 Cm) Hepatocellular Carcinoma Tumors, Artem Boyev, Nirav Thosani, Putao Cen, Jennifer M Bailey-Lundberg, Julie Rowe, Curtis J Wray

Faculty, Staff and Student Publications

Background and objectives

Treatment of hepatocellular carcinoma (HCC) >5 cm is problematic, as patients are often outside transplantation criteria, and cirrhosis compromises curative resection. The purpose of this study was to evaluate survival following treatment with ablation compared to chemotherapy in large HCC.

Methods

This was a retrospective cohort study of the National Cancer Database (NCDB) Participant User File from 2004 to 2017. Patients with HCC >5 cm in diameter treated with ablation versus chemotherapy alone were compared. Inverse probability-weighted propensity scores were used to model treatment assignments in the Cox proportional hazards model.

Results

A total of 14,783 HCC …

Reducing The Incidence Of Acute Care Falls In Medical-Surgical Psychiatric Adult Patients, Ijeoma Nwosu

Doctor of Nursing Practice Final Project Abstract

The purpose of this scholarly project was to implement a multifactorial fall prevention program within a medical-surgical psychiatric unit. The program was intended to reduce the incidence of falls, strengthen staff compliance, and bridge the gap of fall education. The interventions were developed based on evidence-based fall prevention strategies. The project was implemented within a large healthcare organization in the Texas Medical Center (TMC) located in Houston, Texas. The project utilized the Plan-Do-Study-Act (PDSA) framework. Staff were given education prior to implementation and reeducation during the project cycle. Visual guides were created to guide staff and assist with documentation expectations. …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …

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 …

Sexual Health And Relationship Education Needs Of People In Recovery For An Opioid Use Disorder, J Michael Wilkerson, Kathryn R Gallardo, I Niles Zoschke, Hannah L N Stewart, Serena A Rodriguez, Michael U Anosike, Jason Pullin, Sheryl A Mccurdy

Faculty, Staff and Student Publications

People in recovery with histories of sex and drug-linked behavior (SDB) have an increased risk of substance use recurrence. However, sexual health concerns remain largely unaddressed by recovery support services researchers and practitioners. The purpose of this analysis was to describe the sex and relationship concerns of people in recovery for an opioid use disorder living in level II and level III recovery homes. Recovery homes are sober living homes that the National Association for Recovery Residences classifies into four levels based on staffing and service provision. We interviewed 93 residents and thematically analyzed 92 of the resulting transcripts; one …

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 …

Developing Scenario-Based Strategies For Health, Climate, And Environmental Preparedness: The One Health, One Earth Approach, Azar M Abadi, Kyle D Brumfield, Moiz Usmani, Gemma Jiang, T C Chakraborty, Yuzhou Wang, Zhijie Zhou, Cenlin He, Minghao Qiu, Jennifer D Stowell, Douglas Fritz, Sunil Kumar, Qiang Guo, Ying Xiong, Georgia Destouni, Qian Xiao, Xindi C Hu, Kelvin C Fong, Yun Hang, John Nielsen-Gammon, Rima Habre, Jennifer R Bratburd, Christopher W Tessum, Antarpreet Jutla, Rita R Colwell, Gabriel M Filippelli, Thanh H Nguyen

Faculty, Staff and Student Publications

Climate change amplifies many threats to human health. Despite advances in understanding climate change dynamics and impacts, there remains a critical gap in translating scientific knowledge into equitable, and community‐driven health interventions. The inaugural One Earth, One Health workshop sought to explore this gap through human‐centered design exercises involving interdisciplinary researchers from climate and Earth sciences, engineering, epidemiology, microbiology, and environmental health. Although participants did not co‐develop solutions with affected communities, they used stakeholder role‐playing to guide ideation and lay groundwork for actionable plans. Through these methods, participants identified community needs and proposed prototype solutions to alleviate health threats …

The All-Payer Claims Database After The Gobeille Supreme Court Decision: Assessing The Impact On Fatal Opioid-Related Overdose Research, Jack Cordes, Cici Bauer, Dana Bernson, Marc R Larochelle, Wenjun Li, Jiahao Cao, Olaf Dammann, Thomas J Stopka

Faculty, Staff and Student Publications

Objective: To determine the consequences of the Gobeille v. Liberty Mutual Supreme Court decision on the representativeness of the Massachusetts all-payer claims database (APCD). The loss of individuals captured in the APCD may vary demographically, geographically, and in the capture of fatal opioid-related overdose (OOD).

Data sources and study setting: We used 2013-2021 data from the Massachusetts Public Health Data Warehouse (PHD), which links person-level APCD records to other datasets. The APCD includes commercially-insured health claims mandatorily reported pre-Gobeille. Post-Gobeille, reporting from self-insured plans, a subset of commercially-insured plans, became voluntary.

Study design: In a repeated cross-sectional design, we compared …

Affinity-Optimized Trop2 Antibodies Support Potent Antitumor Activity In Antibody-Drug Conjugates, Aiko Yamaguchi, Junping Hong, Leike Li, Kiyotaka Kobayashi, Chisato M Yamazaki, Summer Y Y Ha, Yasuaki Anami, Wei Xiong, Junquan Liu, Zhiqiang An, Ningyan Zhang, Kyoji Tsuchikama

The Brown Foundation: Institute of Molecular Medicine

Background: Trophoblast cell surface antigen 2 (TROP2) is frequently overexpressed in epithelial tumors and is associated with poor prognosis, making it an attractive therapeutic target. Antibody-drug conjugates (ADCs) directed against TROP2 show clinical benefit, but expression in normal tissues such as skin raises concerns about on-target, off-tumor toxicity. Strategies that improve antitumor efficacy without increasing toxicity are needed.

Methods: Using an in-house phage library, we identified and characterized a novel fully human monoclonal antibody recognizing a unique conformational epitope of TROP2 with reduced binding affinity. This antibody was engineered into homogeneous ADCs carrying auristatin and/or duocarmycin payloads. Comparative studies with …

Telomerase Knockout In Myeloid Cells Predisposes Mice To Foam Cell Formation, Dyslipidemia, Lung Fibrosis, And Cardiac Dysfunction, Zhanguo Gao, Yongmei Yu, David Wiggins, Eva M Sevick-Muraca, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

Aging-associated changes in myeloid cells are incompletely understood. One of the culprits of aging is the downregulation of the Tert gene coding for the catalytic subunit of telomerase. Studies of mouse models with Tert knockout (KO) in specific cells have revealed the importance of the telomere-independent noncanonical function of TERT in supporting mitochondrial metabolism and protection from cell senescence. To investigate the role of TERT in myeloid cells (MCs), we analyzed mice with Tert KO in the LysM+ lineage, indelibly labeled with membrane green fluorescent protein (mG). Macrophage numbers and properties in various organs were compared. Changes in the vasculature, …

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 …