Digital Commons Network^™

Spatial2gwas: A Database For Linking Spatial Transcriptomic Regions With Gwas Traits, Xi Hu, Aoqi Wang, Huan Yu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial heterogeneity of gene expression within tissue regions has a critical influence on biological functions, thereby affecting disease pathogenesis. However, systematic associations between spatially resolved transcriptomes and phenotypes, especially in complex diseases, remain underexplored. Here, we developed spatial2GWAS (http://www.spatial2gwas.cn), a comprehensive resource linking spatial transcriptomic (ST) regions with GWAS traits. In the database, we collected 1196 ST slices (human and mouse) from five technologies and 812 GWAS traits spanning 18 phenotype categories and identified 29 701 ST slice-GWAS trait pairs containing 47 492 significant regions. Functional analyses reveal distinct patterns of cell type composition, gene expression, GO/KEGG pathway activation, and …

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

Erratum For Nachman Et Al., “Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors”, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

No abstract provided.

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Corticotropin-Releasing Factor Neurons In The Bed Nucleus Of The Stria Terminalis Modulate Avoidance Behaviors And Feeding, Juan Manuel Romero, Shae-Marie Stafford-Trujillo, Mitzy Mendoza, Pey-Shyuan Chin, Snigdha Srivastava, Mikhail Kochukov, Qingchun Tong, Benjamin Russell Arenkiel

The Brown Foundation: Institute of Molecular Medicine

Introduction: Animals rely on defensive avoidance of exposed or potentially threatening environments as a fundamental survival strategy, often expressing this behavior as thigmotaxis, or a preference for the periphery of an open space. However, researchers still do not understand how neural circuits coordinate avoidance behavior with competing physiological drives such as feeding. In this study, we investigate how corticotropin-releasing factor (CRF)-expressing neurons in the bed nucleus of the stria terminalis (BNST) integrate environmental avoidance and feeding behavior.

Methods: We used adult male and female mice and applied fiber photometry to monitor BNST CRF neuronal activity in vivo. We performed both …

Ventilation-Perfusion Scan: A Functional Imaging Approach To Regional Lung Disease In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Introduction: As a rare genetic disorder defined by defective ciliary motility, Primary Ciliary Dyskinesia (PCD) leads to chronic respiratory complications. A founder variant in the RSPH4A [c.921+3_921+6delAAGT] gene, common in Puerto Rico, impairs ciliary function and contributes to progressive lung disease. Today, the clinical value of ventilation/perfusion (V/Q) scans in PCD has not been thoroughly investigated as well as pulmonary function tests (PFTs) and chest imaging. To explore the role and clinical utility of V/Q scans in PCD.

Methods: Retrospective evaluation of pulmonary function tests, chest imaging, and Tc-99m DTPA ventilation and Tc-99m MAA perfusion scans in ten patients with …

Racial And Ethnic Disparities In Clinical Characteristics And Outcomes In Adults With Encephalitis: A Retrospective Study, Sienna Wu, Rodrigo Hasbun, Ralph Habis, Jordan Benderoth, Ivany Patel, Ashutosh Gupta, Megan Goyal, Arun Venkatesan, John C Probasco, Paris Bean, Ashley Heck, Laya Rao, Rajesh K Gupta

Faculty, Staff and Student Publications

Background and objectives: This study aims to assess whether adult patients with encephalitis from different racial and ethnic backgrounds exhibit significant differences in clinical presentation, diagnostic findings, and outcomes.

Design and methods: A retrospective cohort study was conducted by utilizing the electronic health records of encephalitis patients in the greater Houston and Baltimore areas. Patients were categorized by race/ethnicity into White or ethnic minority (including Black, Hispanic, and Asian patients). Data was analyzed for the presence of significant differences in clinical characteristics between the two groups.

Results: Among 599 patients, 312 (52.1%) were White and 287 (47.9%) were of an …

Accelerating Ai Innovation In Healthcare: Real-World Clinical Research Applications On The Mayo Clinic Platform, Yue Yu, Xinyue Hu, Sivaraman Rajaganapathy, Jingna Feng, Ahmed Abdelhameed, Xiaodi Li, Jianfu Li, Xiaoke Liu, Liu Yang, Nilüfer Ertekin-Taner, Phil Fiero, Soulmaz Boroumand, Richard Larsen, Maneesh Goyal, Clark C Otley, Nansu Zong, Vijay H Shah, John D Halamka, Cui Tao

Faculty, Staff and Student Publications

Artificial intelligence (AI) holds promise for healthcare, but real-world implementation remains difficult. The Mayo clinic platform (MCP) addresses this by providing scalable, multi-institutional, de-identified data and analytical tools. Through four research projects, we demonstrate MCP's ability to support efficient cohort identification, AI model development, and real-world evidence generation. MCP enables broader accessibility and standardization compared to institutional EHRs, positioning it as a powerful platform for advancing translational research and precision medicine.

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Multisite, Multiancestry Genome-Wide Association Study Meta-Analysis Of Functional Seizure Disorder In A Hospital Sample Of 675,680 Patients, Slavina B Goleva, Costin Leu, Yen-Chen Anne Feng, David Burstein, Sanan Venkatesh, Rebecca Birnbaum, Veera M Rajagopal, Peter Straub, Jakob Christensen, Jocelyn F Bautista, Robyn M Busch, Imad M Najm, Jakob Grove, Anders D Børglum, Georgios Voloudakis, Panos Roussos, Jordan Smoller, Dennis Lal, Lea K Davis

Faculty, Staff and Student Publications

Background: Functional seizures (FS) are paroxysmal episodes that phenotypically resemble epileptic seizures but are not associated with brain epileptiform discharges; they are also known as psychogenic nonepileptic seizures. The exact etiology and pathophysiology of FS is unknown; however, trauma and stress-related disorders are known risk factors.

Methods: We used a validated algorithm applied to electronic health records to identify individuals with FS in 6 international biobanks and hospital sites. We conducted a multisite FS genome-wide association study (GWAS) meta-analysis, including 10,910 FS cases (9040 predicted European ancestry [EA] and 1870 predicted African ancestry [AA]) and 664,500 (561,150 EA and 103,350 …

Clinical Informatics Education To Advance Learning Health Systems: A Scoping Review, Alexandra Zingg, L Ida Tovar, Laura Witte, Kelsey L Koym, Kyler Godwin

Library Staff Publications

Introduction: Learning health systems leverage clinical data and knowledge to advance healthcare quality. Effective training in informatics concepts and tools is essential for medical trainees to become health system experts and contributors to positive organizational change. The objective of this study is to summarize characteristics of existing clinical informatics training programs and map these to recommended Learning Health System informatics competencies. We aim to answer the following research questions: (1) How are academic medical institutions implementing informatics education initiatives for medical trainees? (2) Are these initiatives implementing recommended informatics competencies? and (3) How effective are these initiatives according to established …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Examining Widely Held Propositions On Human Dietary Protein Needs And Benefits: A Critical Review Of The Science That Shapes Both The Data And Our Understanding Of An Essential Macronutrient, Mitchell M Kanter, Sally Aaron, Steven N Austad, Andrew W Brown, Nicholas A Burd, Wayne W Campbell, Mark Cope, Teresa A Davis, John W Erdman, Miguel Freitas, Kristen Hicks-Roof, Samuel Klein, Wantanee Kriengsinyos, Dudley W Lamming, Donald K Layman, Heather J Leidy, Kevin C Maki, Richard D Mattes, Shalene Mcneill, Daniel R Moore, Stefan M Pasiakos, Stuart M Phillips, David Raubenheimer, Wendy Reinhardt, Nancy R Rodriguez, Stephen Simpson, Hans H Stein, Luc J C Van Loon, Connie M Weaver, David B Allison

Children’s Nutrition Research Center Staff Publications

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, …

Limosilactobacillus Reuteri Alleviates Proinflammatory T-Cell-Mediated Liver Injury And Transcriptomic Changes In Immunocompromised Mice, Ana Fadhel Alvarez, Zheng Yin, Beanna Okeugo, Alexander Banerjee, Meng Luo, Christopher M Taylor, Salomea Giorgberidze, Vaishali Harne, Rambabu Majji, Melissa N Munroe, Ji Ho Suh, Stephen T C Wong, Kang Ho Kim, Hari Krishna Yalamanchili, Suhair Al Salihi, Jon Marc Rhoads, Yuying Liu

Children’s Nutrition Research Center Staff Publications

Background: A deficiency of immunosuppressive regulatory T cells, as seen in scurfy (SF) mice or in IPEX syndrome in humans, can lead to multiorgan inflammation. Oral administration of the probiotic Limosilactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in SF mice. It remains unclear how DSM 17938-educated SF-CD4+ T cells modulate T-cell-liver communication.

Methods: To characterize CD4+ T cells from SF mice orally administered DSM 17938 (Prob-SF-CD4+ T cells) and to compare them with CD4+ T cells from SF mice (SF-CD4+ T cells), cells isolated from SF spleens were …

Cross-Sectional And Longitudinal Relationships Between Abdominal Fat Depots And Cardiometabolic Risk In A Sample Of Mexican Adolescents, Luis Ortíz-Hernández, Erica G Soltero, Miguel Camejo, Jesús Valdes

Children’s Nutrition Research Center Staff Publications

Background: The relationship between abdominal fat depots and cardiometabolic risk among youth is inconclusive due to the cross-sectional nature of existing studies and limitations in assessment methods. In this study, we examined cross-sectional and longitudinal associations of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with cardiometabolic risk indicators among Mexican adolescents.

Methods: Participants (n = 169 at baseline and 134 at follow-up) were assessed for diastolic or systolic blood pressure (DBP or SBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, and insulin. VAT and SAT were measured using magnetic resonance imaging. Measures …

Sustainable Community-Wide Model To Enhance Cancer Data Usage And Utility, Emily S Boja, Mousumi Ghosh, Ying Huang, Tung-Shing Mamie Lih, Rawan Shraim, Gregory Wheeler, Diana Thomas, Rakesh Khanna, Stephanie Sandor, Jinghui Zhang, Sapna Oberoi, Nicolas J Llosa, Aditya Suru, Fernanda Silva Michels, Eric Durbin, Anna Fernandez, Lucy Han, James Galbraith, Yin Lu, Brian Furner, James H Tanis, Michael Watkins, David Higgins, Gavriel Matt, Xin Zhou, Yang Li, Marcin Cieslik, Jamie Estill, Michael Sierk, Yanling Sun, Weiping Ma, Joseph Flores-Toro, Freddie Pruitt, Subhashini Jagu, Elmer A Fernández, Daniela Orschanski, Stephanie J Spielman, Jaclyn Taroni, Trinh Nguyen, Brian Capaldo, Erin Beck, Tanja Davidsen, Johanna Goderre Jones, Minghong Ward, Anne Sturcke, Jennifer M Torres Del Valle, Sean Hanlon, Danielle Daee, Brandon Wright, Nathaniel Boyd, Heather Basehore, Liang Liu, Ying Hu, Daoud Meerzaman, Huiqing Li, Ying Wu, Gregory H Reaman, Erin Rudzinski, Jack F Shern, Brigitte Widemann, Warren Kibbe, Jaime Guidry Auvil

Children’s Nutrition Research Center Staff Publications

Despite vast investments in data collection, generation, and sharing from childhood cancer studies, for example, Gabriella Miller Kids First Research Program, Childhood Cancer Data Initiative, and other efforts, secondary use of data remains a challenge especially for rare diseases. The National Cancer Institute (NCI) Office of Data Sharing (ODS) aimed to promote FAIR (Findable, Accessible, Interoperable, Reusable) data sharing practices to enhance data utility, accelerate discovery, and foster interdisciplinary collaboration. NCI ODS launched its inaugural Data Jamboree focusing on childhood cancer alongside its third Annual Symposium in September 2025. Over 120 participants with diverse backgrounds coalesced into 23 multidisciplinary teams …

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Latent Classification Of Time-Dependent Transition Rates In Longitudinal Binary Outcome Data, Joonha Chang, Wenyaw Chan

Faculty, Staff and Student Publications

Continuous-time Markov chain (CTMC) models and latent classification methods are commonly used to analyze longitudinal categorical outcomes in medical research. While CTMC models are popular for their simplicity and effectiveness, their assumption of constant transition rates presents limitations in capturing dynamic behaviors. To address this, non-homogeneous continuous-time Markov chains (NH-CTMCs) have been developed, incorporating time-varying transition rates to enhance model flexibility. In this study, we leverage closed-form transition probabilities for a fully ergodic two-state NH-CTMC model and propose a latent class clustering approach to identify heterogeneous transition rate patterns within the population. We emphasize the potential advantages of these models …

“If He Did It, I Can Do It, Too. I Can Change My Life Around”: The Social Model Of Recovery Within The Context Of Recovery Homes Accepting Residents Prescribed Medications For Opioid Use Disorder, Jodie M Dewey, Kathryn R Gallardo, Meenakshi S Subbaraman, Amy A Mericle

Faculty, Staff and Student Publications

Introduction: This paper provides an in-depth examination of examines four recovery residences, that serve individuals prescribed medications for opioid use disorder (MOUD). The study has two primary aims: first, to deepen understanding of how recovery residences adopt and operationalize Social Model of Recovery principles; and second, to identify gaps in staff integration of residents receiving MOUD-gaps that may either support or undermine the integrity of the social model within these settings.

Methods: We conducted semi-structured interviews with 17 residents receiving MOUD living in four participating recovery homes. The interviews were conducted between August 2022 and January 2024 using a semi-structured …

Pregnancy And Breastfeeding Are Associated With Less Later-Life Cognitive Decline In A Longitudinal, Prospective Cohort, Molly M Fox, Jennifer E Bramen, Dayoon Kwon, Mark A Espeland, Yijia Sun, Li Zhang, Aladdin H Shadyab, Ramon Casanova, Joann E Manson, Marcus Y Chang, Verna R Porter, Leslie V Farland, Qian Xiao, Robert A Wild, Prabha Siddarth, Carolyn J Crandall

Faculty, Staff and Student Publications

Introduction: The brains of female mammals evolved to undergo structural and functional changes during pregnancy and lactation, equipping them for motherhood. However, long-term cognitive health implications of these adaptations in women are poorly understood.

Methods: In the Women's Health Initiative (WHI) Memory Study (WHIMS; n = 7427) and WHI Study of Cognitive Aging (WHISCA; n = 2304), postmenopausal women completed reproductive history interviews, annual global cognitive assessment from mean age 70 for up to 13 years, and multi-domain cognitive testing for up to 8 years.

Results: Each additional month pregnant was associated with higher scores of global cognition. Each additional …