Medicine and Health Sciences Commons^™

Sarcopenic Obesity And Dementia Risk: Primary Associations And Landmark Analyses Of Muscle Strength And Body Composition Trajectories, Zhongyang Guan, Blossom C.M. Stephan, Lorenzo M. Donini, Justyna Godos, Giuseppe Grosso, Leticia Radin Pereira, Carla M. Prado, Carlos J. Toro-Huamanchumo, Jonathan C.K. Wells, Marc Sim, Mario Siervo

Research outputs 2022 to 2026

Background and aims: Sarcopenic obesity (SO) has been proposed as a risk factor for cognitive impairment. Yet evidence is inconsistent and often limited by heterogeneous definitions and lack of longitudinal assessments. This study aimed to examine associations of SO with all-cause and subtype-specific dementia, and to assess dose–response patterns and how longitudinal changes in body composition and muscle strength relate to dementia risk. Methods: We included 489,972 adults (mean age 56.5 ± 8.1 years) followed for a median of 13.6 years. SO was defined using the Sarcopenic Obesity Global Leadership Initiative (SOGLI) criteria. Cox models estimated hazard ratios (HRs) for …

Extending Genome-Wide Association Studies To Admixed Cohorts With High Degrees Of Relatedness, Taotao Tan, Alejandra Vergara-Lope, José Jaime Martínez-Magaña, Nirav N Shah, Yi-Sian Lin, Kai Yuan, Jaime Berumen, Jesus Alegre-Díaz, Pablo Kuri-Morales, Roberto Tapia-Conyer, Joel Gelenter, Janitza L Montalvo-Ortiz, Wei Zhou, Jason M Torres, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

Admixed populations comprise a large portion of the human population worldwide, but are often excluded from genome-wide association studies (GWASs) due to analytic challenges. Our group developed Tractor, a local-ancestry-informed GWAS tool designed for admixed samples that produces accurate ancestry-specific effect sizes and boosts the discovery power to identify ancestry-enriched loci. However, Tractor operates under an assumption of unrelated samples. Here, to address this gap, we propose Tractor-Mix, which allows for well-calibrated association studies in datasets containing admixed samples with relatedness. Extensive simulations show that this method is competitive with other state-of-the-art approaches that do not produce ancestry-specific results. Empirical …

A Blended Genome And Exome Sequencing Method Captures Genetic Variation In An Unbiased And Cost-Effective Manner, Toni A Boltz, Benjamin B Chu, Matthew Defelice, Calwing Liao, Julia M Sealock, Robert Ye, Jacqueline I Goldstein, Lerato Majara, Jack M Fu, Susan K Service, Lingyu Zhan, Sarah E Medland, Sinéad B Chapman, Simone Rubinacci, Jonna L Grimsby, Tamrat Abebe, Melkam Alemayehu, Fred K Ashaba, Elizabeth G Atkinson, Tim B Bigdeli, Amanda B Bradway, Harrison Brand, Lori B Chibnik, Samuel Deluca, Ana M Diaz-Zuluaga, Abebaw Fekadu, Michael Gatzen, Bizu Gelaye, Stella Gichuru, Marissa L Gildea, Toni C Hill, Hailiang Huang, Kalyn M Hubbard, Wilfred E Injera, Roxanne James, Moses Joloba, Christopher Kachulis, Phillip R Kalmbach, Rogers Kamulegeya, Gabriel Kigen, Soyeon Kim, Nastassja Koen, Edith K Kwobah, Joseph Kyebuzibwa, Seungmo Lee, Niall J Lennon, Penelope A Lind, Esteban A Lopera-Maya, Johnstone Makale, Serghei Mangul, Justin Mcmahon, Pierre Mowlem, Henry Musinguzi, Rehema M Mwema, Noeline Nakasujja, Carter P Newman, Lethukuthula L Nkambule, Conor R O'Neil, Ana Maria Olivares, Catherine M Olsen, Linnet Ongeri, Sophie J Parsa, Adele Pretorius, Shengying Qin, Raj Ramesar, Faye L Reagan, Chiara Sabatti, Jacquelyn A Schneider, Welelta Shiferaw, Christine Stevens, Anne Stevenson, Erik Stricker, Rocky E Stroud, Jessie Tang, Megan Townsend, David Whiteman, Mary T Yohannes, Mingrui Yu, Kai Yuan, Dickens Akena, Lukoye Atwoli, Symon M Kariuki, Karestan C Koenen, Charles R J C Newton, Dan J Stein, Solomon Teferra, Zukiswa Zingela, Carlos N Pato, Michele T Pato, Carlos Lopez-Jaramillo, Nelson B Freimer, Roel A Ophoff, Loes M Olde Loohuis, Michael E Talkowski, Benjamin M Neale, Daniel P Howrigan, Alicia R Martin

Duncan NRI Faculty and Staff Publications

Here we developed and deployed the blended genome exome (BGE) method, a DNA library approach that generates low-pass whole-genome (1–4× mean depth) and deep whole-exome (30–40× mean depth) data in a single sequencing run. BGE is cost-effective, empowers most genomic discoveries possible with deep whole-genome sequencing and captures global common single-nucleotide polymorphism diversity. We applied BGE to sequence >53,000 samples from the PUMAS Project (Populations Underrepresented in Mental Illness Associations Studies), including African, African American and Latin American populations. Imputed genotypes showed high concordance with Illumina Global Screening Array calls (R2 ≥ 95% for minor allele frequency ≥1%; …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal

Faculty, Staff and Students Publications

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.

Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios …

Dupilumab Versus Placebo In Adults And Adolescents With Eosinophilic Gastritis (Degas): A Double-Blind, Placebo-Controlled, Phase 2, Multicentre, Randomised Controlled Trial, Nirmala P Gonsalves, Evan S Dellon, Kara L Kliewer, Tetsuo Shoda, Regina Yearout, Seema S Aceves, Nicoleta C Arva, John A Besse, Julie M Caldwell, Mirna Chehade, Amaziah Coleman, Margaret H Collins, Sara Anvari, Gary W Falk, Sandeep K Gupta, Girish Hiremath, David A Katzka, Paneez Khoury, John Leung, Calies Menard-Katcher, Paul Menard-Katcher, Kathryn A Peterson, Maria A Pletneva, Amanda K Rudman Spergel, Jonathan M Spergel, Tatyana Vaysman, Joshua B Wechsler, Benjamin L Wright, Guang-Yu Yang, Xue Zhang, Meijian Zhou, Ashish Bansal, Bram P Raphael, Amr Radwan, Jennifer Maloney, Antonio Martin, Yamo Deniz, Glenn T Furuta, Lisa J Martin, Marc E Rothenberg

Faculty, Staff and Students Publications

Background: Eosinophilic gastritis currently has no approved treatments and is postulated to be driven by type 2 inflammation. Dupilumab blocks type 2 cytokines IL-4 and IL-13 and has efficacy in multiple diseases characterised by type 2 inflammation, including eosinophilic oesophagitis. We aimed to assess the efficacy and safety of dupilumab in patients with eosinophilic gastritis.

Methods: DEGAS was a proof-of-concept, phase 2, multicentre, randomised controlled trial consisting of a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12-70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field …

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Alex J Katz, Haley Haskett, Kubra M Bozkanat, Aoife Corcoran, Lauren M C Grant, Antoinette Wannes Daou, Sin Tran, Esra Caylan, Alfin Vicencio, Dan T Benscoter, Cherie A Torres-Silva, Sara M Zak, Gregory Burg, Lisa R Young, Pelton Phinizy, Shailendra Das, Richard Paul Boesch, Erik B Hysinger, Joseph Piccione

Faculty, Staff and Students Publications

Rationale: Cryotherapy and its diagnostic analogue, cryobiopsy, are emerging techniques via bronchoscopy with a wide range of clinical applications. While the use of cryotherapy and cryobiopsy has been established in adult pulmonary medicine, pediatric data describing the indications, procedural specifics, outcomes, and complications are limited.

Objective: To describe the indications, procedural specifics, outcomes, and complications of cryotherapy and cryobiopsy use in pediatric bronchoscopy.

Methods: A multicenter retrospective observational study was conducted at 5 pediatric hospitals in the United States. Patients aged 0 to 21 years who underwent cryotherapy or cryobiopsy via bronchoscopy between January 2017 and January 2025 were included. …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

Musical Training Increases Anticipatory Responding And Predictive Control In Sequence Learning, Li Ann Leow, Jarrad Lum, Sara Johnson, Emily Corti, Welber Marinovic

Research outputs 2022 to 2026

Musicians demonstrate advantages in acquiring motor sequences, showing faster learning and better explicit sequence knowledge than non-musicians. However, it is unclear whether this advantage extends beyond acquisition to the consolidation phase, which is when newly learned skills stabilize and become resistant to interference. Additionally, while interference from executing competing motor tasks is well-established, less is known about whether purely sensory information presented after learning can disrupt consolidation of a bimodal motor sequence. We investigated how post-acquisition sensory interference affects performance of a learned audio-visual sequence, and whether musical training moderates this vulnerability. Participants first learned an explicit sequence in a …

Hippo Signaling Regulates Cuticle Pigmentation And Dopamine Metabolism In Drosophila, Shelley B Gibson, Samantha L Deal, Ye-Jin Park, Bo Sun, Yanyan Qi, Jung-Wan Mok, Hyung-Lok Chung, Hongjie Li, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise …

Engagement Of Understudied Populations As Community Change: The South Texas Adrc Model, Gladys E. Maestre, Neela K. Patel, Rosa V. Pirela, Robin C. Hilsabeck, Kendra Stine, Neyra García, Roberto Reyes, Omar Oropeza, Cristian Maestre, Jesus D. Melgarejo, Sarah Williams-Blangero, Ney Alliey Rodriguez

School of Medicine Publications

Many populations experiencing the highest burdens of Alzheimer's disease and related dementias remain understudied, in part because traditional recruitment and retention models are insufficient to support sustained engagement. The Outreach, Recruitment, and Engagement Core (OREC) of the South Texas Alzheimer's Disease Research Center reconceptualized participant recruitment as a long-term system change in a Hispanic-majority, urban–rural region. OREC institutionalizes shared power through community advisory governance, aligns research protocols with local lived realities (through patient navigators, community health workers/promotores, and decentralized access points), and employs a data-driven feedback loop for continuous improvement. In 1 year, 46 outreach events touched 10,134 individuals (71% …

Dissecting Ms4a4a Function In Microglia And Its Role In Alzheimer’S Disease Pathogenesis, Emma Pascal Danhash

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies have begun to uncover the complex genetic architecture of Alzheimer's disease (AD). Expression of many AD risk loci is enriched in microglia, the resident immune cells of the brain. Common variants near the MS4A gene family have been associated with AD risk and altered soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF). MS4A4A is a microglial gene that encodes a tetraspan membrane protein that regulates anti-inflammatory responses in macrophages. However, the mechanism by which MS4A4A contributes to microglial function and AD pathogenesis remains unknown. In this dissertation, I leveraged a …

Retrospective Comparison Of Prostate Vmat Boost Plans With Central Versus Offset Isocenter Placement, Carly Shefffield

Masters Projects

This retrospective study evaluated the effects of isocenter placement on dosimetric outcomes for sequential prostate boost planning using volumetric modulated arc therapy (VMAT). Ten patients previously treated with whole pelvis radiation therapy (WPRT) followed by a sequential boost were selected. For each patient, two VMAT boost plans were created using identical planning objectives and beam arrangements. One plan was optimized using the original WPRT isocenter, while the second plan had the isocenter placed at the center of the boost planning target volume (PTV). Target coverage, conformity, and organ-at-risk (OAR) dose metrics were compared between the two planning techniques. Both plans …

Extracorporeal Rescue In Massive Pulmonary Embolism: A Case Of Chronic Thromboembolic Pulmonary Hypertension Unveiled, Kenzo Ramos, Kari Gorder

Journal of Shock and Hemodynamics

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare yet curable cause of pulmonary hypertension from unresolved pulmonary emboli. We present the case of a 48-year-old man with progressive dyspnea and leg swelling, who was found to have bilateral pulmonary emboli with right heart strain. He developed cardiac arrest during thrombectomy, requiring emergent veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Further evaluation revealed acute emboli superimposed on CTEPH. After incomplete thrombectomy and persistent instability, he underwent successful pulmonary endarterectomy with ECMO decannulation, leading to recovery of right ventricular function and discharge in stable condition. This case illustrates that previously unrecognized CTEPH may …

Intermembrane Coupling Between Bcl-Xl And The Ip3 Receptor Supports Local Ca2+ Transfer At Er-Mitochondrial Contacts, Arijita Ghosh, David Weaver, Chi Li, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Bcl-xL, an anti-apoptotic Bcl-2 family protein, engages laterally with Bak/Bax in the outer mitochondrial membrane (OMM) to inhibit apoptosis and interacts with the IP₃ receptor Ca²⁺ channels (IP3Rs) in the endoplasmic reticulum (ER) membrane to control Ca²⁺ release. It is unknown if OMM-localized Bcl-xL can also interact in trans with IP3Rs at ER-mitochondrial contacts to form a tethering complex that supports IP3R-mediated local Ca²⁺ transfer from ER to mitochondria. We establish that IP3R-mitochondria Ca²⁺ signal propagation depends on Bcl-xL. By targeting Bcl-xL specifically to different subcellular compartments, we find that OMM-localized Bcl-xL increases the efficacy …

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

"It Doesn't Matter Where Ocd Comes From," Or Does It?, Caitlin M Pinciotti, Ryan J Mccarty, Gabriella T Ponzini

Faculty, Staff and Students Publications

Purpose of review: This review critically evaluates the claim that etiology is not relevant to cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). Research on the clinical presentation and treatment outcomes associated with traumatic/stressor and biological etiologies is presented.

Recent findings: The extant literature demonstrates varying clinical utility across the reviewed etiologies. Traumatic/stressor etiologies show the most consistent and robust evidence of clinical utility, demonstrating compelling associations with clinical presentation and treatment outcomes, while also being amenable to existing evidence-based approaches. Medical conditions (e.g., Pediatric Acute onset Neuropsychiatric Syndrome) and neurobiological factors also demonstrate considerable associations with OCD presentation, yet …

Bridging The Gap In Science Research: Preparing Students For College- Level Research In The Sciences, Victoria Helwig, Yaoguang Li

UConn Library Presentations

Many first-year students enter college unprepared to fully engage with scientific literature and academic library resources. Drawing on experiences from academic librarians working with STEM students, this session explores common gaps in science research skills, including navigating databases, identifying scholarly sources, and understanding the structure of scientific literature. Participants will be introduced to practical strategies and classroom-ready activities to better prepare students for college-level research. Discussion questions: What science research skills do students struggle with most when entering college? How can high school instruction better support these skills? Where can librarians and educators collaborate to support student success?

Notch Signaling Regulates The Secretion Of Pro-Metastatic Factors In Extracellular Vesicles In Liposarcoma, Menchus Quan, Yi-Kai Liu, Ying Zhao, Madeline Kay, Kai Sun, Timothy P Gavin, Raphael E Pollock, W Andy Tao, Shihuan Kuang

The Brown Foundation: Institute of Molecular Medicine

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that …

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun

The Brown Foundation: Institute of Molecular Medicine

Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, but the role of macrophage-intrinsic extracellular proteolysis in immunometabolic regulation remains unclear. Matrix metalloproteinase-14 (MMP14), a membrane-bound protease, is strongly induced during monocyte-to-macrophage differentiation and further elevated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacological inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, phagocytosis, and inflammatory activation in response to obesity-associated adipose tissue signals. Mechanistically, MMP14 promoted inflammatory programming by increasing endotrophin generation and enhancing TLR4-NFκB signaling. MMP14 also reprogrammed macrophage lipid metabolism by suppressing lipolysis and promoting lipid accumulation, altering metabolic communication with neighboring …

Intouch Week Of July 27, 2026, New York Medical College

InTouch

• NYMC Receives $2.7 Million HECap Award
• The Inquiring Minds of Student Research
• Grasslands Garden Blooms into a Community Gathering Space
• Incoming M.D. Students Celebrate Completion of Pre-Matriculation Program
• White Plains Youth Bureau Explore Health Care Careers at NYMC
• Hispanics with Met-ALD Face Higher Rates of Serious Liver Complications
• TCDM Welcomes Class of 2030
• Faculty Spotlight: Jin Li, M.D., Ph.D. ’01: A Lifetime Dedicated to Neurology, Education, and Community Service

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 …

Simbinder-If: Structure-Aware Antibody Affinity Optimization Via Efficient Preference Learning, Xinyan Zhao, Yi-Ching Tang, Rivaaj Monsia, Victor J Cantu, Ashwin Kumar Ramesh, Siyu Yang, Xiaozhong Liu, Zhiqiang An, Xiaoqian Jiang, Yejin Kim

The Brown Foundation: Institute of Molecular Medicine

Motivation: Antibody therapeutic efficacy depends on high-affinity target engagement, yet laboratory affinity maturation is slow and costly. Most protein language models (PLMs) lack explicit training for high affinity, and current preference optimization methods introduce computational overhead without clear affinity improvements. Therefore, structure-aware and parameter-efficient approaches for antibody affinity optimization are urgently needed.

Results: We propose SimBinder-IF, a structure-aware antibody optimization model trained by freezing the Evolutionary Scale Modeling inverse folding (ESM-IF) structure encoder and fine-tuning only its decoder via Simple Preference Optimization (SimPO) to prefer stronger binders. In generalization tests across seven held-out complexes (93 477 mutants), SimBinder-IF shows a …

Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow

MUSC Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest five-year survival rates among cancers and is characterized by near-ubiquitous occurrence of oncogenic KRAS mutations. Oncogenic KRAS activates several downstream pathways, including ERK 1/2 MAPK and PI3K, which are critical for PDAC. However, accumulating evidence suggests that PI3K activity can be maintained independent of oncogenic KRAS. The high prevalence of KRAS^G12R in PDAC challenges the prevailing model of KRAS-driven PI3K activation, as this mutant is defective in direct engagement with PI3Kα. These observations raise important questions regarding how PI3K signaling is sustained in PDAC. Here, we investigated KRAS-independent mechanisms that …

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: …

Segmented Profile Analysis (Sepa): Plane-Wise Decomposition Of Within-Person Variation Via Ipsatized Singular Value Decomposition, Se-Kang Kim, Joe Grochowalski

Faculty, Staff and Students Publications

Traditional profile analyses summarize multivariate person data with overall mean levels and relative patterns, but existing methods often blur these sources of variation or reduce each individual to a single best-fitting profile. Segmented Profile Analysis (SEPA) offers a unified, ipsatized singular-value decomposition (SVD) framework that decomposes individual profiles into orthogonal level (LE) and pattern (PE) effects and, crucially, introduces plane-wise segment profiles (summaries of each person's response pattern within each variable-contrast dimension) as primary person-oriented objects. Within each low-dimensional plane, SEPA defines a projected response pattern (segment profile), domain-person cosines that index variable-by-variable alignment, and plane-fit correlations that summarize how …

Wellness Literature Review – 2025, Martin Huecker, Brian A. Ferguson

Journal of Wellness

Introduction: Clinician well-being remains a persistent challenge, with ongoing burnout and psychological distress despite efforts by systems and individuals. This Journal of Wellness annual review covers studies published in 2025.

Methods: The Editors searched PubMed and Google Scholar for prospective and interventional studies / clinical trials in humans, with focus on well-being. Authors utilized artificial intelligence (AI)–based large language model (LLM) (ChatGPT, OpenAI^TM) to assist with preliminary identification of relevant studies, however authors noted significant AI-associated errors and outright misrepresentations requiring hand curated product generation and manual PubMed searches.

Literature in Review: We continue to appreciate a shift …

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 …

Identification Of Acute Kidney Injury In African Children Hospitalized With Malaria: A Multinational Individual Participant Data Meta-Analysis, Caitlin Bond, Anthony Batte, Folake Afolayan, Nicholas M Anstey, Quique Bassat, Philip A Bejon, James A Berkley, Rhys D R Evans, Stuart L Goldstein, Michael T Hawkes, Olayinka Ibrahim, Peace Imani, Chandy C John, Kevin C Kain, Claire Liepmann, Kevin Marsh, Ruth Namazzi, Margaret Nakuya, Nicole O'Brien, Lere P Oluwadare, Robert O Opoka, Jonathan Sserunkuuma, Hunter Wynkoop, Andrea L Conroy, Malaria Associated Kidney Injury And Disease Consortium In Africa (Makid-Africa)

Faculty, Staff and Students Publications

Background: Historically, acute kidney injury (AKI) has been an underappreciated complication in children with severe malaria. We conducted an individual patient data meta-analysis to model the impact of AKI and its complications on inpatient mortality in African children hospitalized with malaria.

Methods: Studies were identified using MEDLINE, EMBASE, Scopus, and PubMed with no language restrictions, as well as through outreach at scientific meetings. Investigators were contacted about participation in the study. Eligible studies included African children hospitalized with Plasmodium falciparum malaria, a serum creatinine measurement, and mortality assessed. The primary exposure was AKI, defined using Kidney Disease Improving Global Outcomes …