Digital Commons Network^™

Intermittent High-Fat, High-Sugar Access During Adolescence Drives Binge-Restriction Feeding And Reduced Weight Gain In A Food Unpredictability Model, Calvin G. Miller

CMC Senior Theses

Food insecurity affects nearly 48 million Americans and 318 million people worldwide, with very low food security disrupting normal eating habits through “feast-or-famine” episodes characterized by cycles of food overconsumption followed by restriction. This dietary pattern alters dopamine signaling within the mesocorticolimbic system — brain circuitry intimately linked to reward processing. This system includes the ventral tegmental area (VTA) and prefrontal cortex (PFC). Overstimulation can be promoted through sporadic high-fat, high-sugar diet (HFHSD) exposure, promoting dopamine neuron architecture alterations and binge-eating behavior. Adolescence represents a vulnerable window, as mesocorticolimbic dopamine projections undergo maturation during this period. Though evidence links food …

The Influence, Dependency, And Targeting Of Fatty Acid Uptake In Er+ Breast Cancer, Abigail E. Goen

Dartmouth College Ph.D Dissertations

Estrogen Receptor-positive/ Human Epidermal Growth Factor 2-negative, breast cancer (ER+/HER2- BC) is the most prevalent subtype of BC, impacting millions of individuals. Although early screening and treatment with endocrine therapy has greatly enhanced survival, this subtype sustains a steady increase of risk for recurrent disease for decades after diagnosis, indicating the persistence of residual cancer cells that are capable of maintaining dormancy for >20 years prior to metastatic outgrowth. Dormant cells reprogram metabolic pathways which can be profoundly influenced by the tumor microenvironment in promoting quiescence or proliferation. Fatty acid oxidation dependency has been noted as a hallmark of drug …

Maesa Ramentacea Leaf Extract Protects Against Gentamicin-Induced Nephrotoxicity In Wistar Rats By Modulating Renal Oxidative Stress, Inflammation And Apoptosis, Fahmida Akter, Md Shafiqul Islam Sovon, Baizid Hossain, Md Ariful Islam, Subrato Das, Anik Biswas, Md Sohorab Uddin, Md Mahmudul Hasan

Faculty Publications

Background: Gentamicin-induced nephrotoxicity continues to be a significant clinical concern, while effective and safe protective options remain limited. The nephroprotective potential of Maesa ramentacea has not yet been explored. To address this gap, the present study investigated the ethanolic leaf extract of M. ramentacea (MR-LEE) for its effects on gentamicin-induced kidney injury in Wistar rats. Methods: GC-MS profiling was employed to identify bioactive metabolites. Rats were categorised into five groups: control, gentamicin (100 mg/kg), gentamicin combined with silymarin (100 mg/kg), gentamicin combined with MR-LEE (200 mg/kg) and gentamicin combined with MR-LEE (400 mg/kg). Renal biomarkers, oxidative stress indicators, inflammatory and …

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …

Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone …

Insulin Resistance As A Mediator Of Physical Activity's Effects On Beta-Amyloid Accumulation And Tau Phosphorylation: A Scoping Review, Michael G. Slee, Joanne Scotney, Stephanie R. Rainey-Smith, Kirk I. Erickson, Hamid R. Sohrabi, Giuseppe Verdile, Belinda M. Brown

Research outputs 2022 to 2026

Background Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective …

The Impact Of Gastric Sleeve And Roux-En-Y Gastric Bypass On Chief Cell Function And Protein Digestion In Obese Patients, Garikoitz Mikel Gainza

Honors Undergraduate Theses

Obesity has become one of the largest global health concerns of the 21^st century, correlating with numerous associated diseases. To help address the growing prevalence and burden of obesity, sleeve gastrectomy and Roux-en-Y gastric bypass have become two commonly performed surgical procedures done to promote weight loss by altering the anatomical structure of the stomach and surrounding organs of the gastrointestinal system. Although the benefits of improved metabolism linked to these surgical procedures are well studied, their impact on the physiology of gastric cells, and more specifically chief cells as they relate to protein digestion post-surgery, is yet to …

An Anti-Adhesive Compound Modulating The Production Of Staphylococcus Aureus Cell Wall-Anchored Proteins, Allison C. Leonard, Ruina Bao, Cindy Menjivar, Megan J. Myers, Telmo O. Paiva, Zhiyong Zheng, Kirsten A. Berry, Kenneth W. Bayles, Ronald S. Flannagan, Yves F. Dufrêne, Jeffrey L. Bose, David E. Heinrichs, Georgina Cox

Journal Articles: Pathology and Microbiology

As one of the leading global causes of death associated with antimicrobial resistance, Staphylococcus aureus frequently colonizes the human nasal cavity and adheres to keratinized skin, establishing reservoirs that drive subsequent infections and emphasize the need for new decolonization strategies. Using a high-throughput, whole-cell screening platform, here we identify geranylgeranoic acid (GGA), a naturally occurring polyunsaturated, branched-chain fatty acid, as having dual activity against methicillin-resistant S. aureus (MRSA). At elevated concentrations, GGA exhibits microbicidal effects, whereas at sub‑microbicidal doses, it effectively inhibits MRSA adhesion to keratin, fibronectin, fibrinogen, and immunoglobulins. GGA possesses anti-adhesive activity against a panel of multidrug-resistant S. …

Applicability Of The Cleveland Clinic Scoring Tool For The Risk Prediction Of Acute Kidney Injury After Adult Cardiac Surgery., Ahmed A Faragalla, Ahmed M Elshiemy, Wael S Nekhila, Sherif M Elboghdady

Journal of Medicine in Scientific Research

Background Post-cardiac surgery acute kidney injury (AKI) is a significant complication associated with increased mortality, longer ICU stays, and higher healthcare costs. The Cleveland Clinic Scoring Tool (CCST) aids preoperative risk evaluation, facilitating tailored prevention strategies. Aim This study evaluates the relevance of the CCST in prospectively assessing AKI risk in adult patients undergoing various cardiac surgeries. Methods This prospective cohort study (tertiary centre, Jan 2021-Aug 2023) assessed the CCST for preoperative AKI risk in adult open-heart surgery (OHS) patients. Consenting adults (≥18) undergoing elective/emergency OHS were included, excluding those with pre- AKI (KDIGO), dialysis-dependent ESRD, aortic dissection, shock, or …

The Effects Of Habitual Temperature And Diet On Crayfish Physiological Processes, Tyler D. Deramo, Sunny Rana, Victor Popoviciu

Williams Honors College, Honors Research Projects

We will use crayfish to test the individual and combined effects of temperature and diet to see how they impact physiological processes such as metabolism, growth rate, molting patterns, and behavioral analysis. A total of forty-eight crayfish will be used throughout the experiment, and they will be housed in separate containers. A plant-based diet (consisting of fresh kale) and an animal-based diet (consisting of dried bloodworms) will be tested alongside room temperature (~18 degrees Celsius) and a warmer habitual temperature (~24 degrees Celsius). Metabolism will be measured via O2 consumption, and growth will be measured by weighing and measuring the …

Bovine Colostrum And Late-Onset Sepsis In Premature Infants: A Multicenter Randomized Controlled Trial (Bcsp Study), Hany Wifky Gendy Michael, Hassan Mohamed Hassan Mohamed, Dalia Abu Elmaaref Mohamed Ibrahim

Journal of Medicine in Scientific Research

Aim: Neonatal sepsis and necrotizing enterocolitis (NEC) have a great impact on morbidity and mortality in immature newborns. We performed our trial to examine the impact of enteral bovine colostrum administration upon late neonatal sepsis in premature newborns. Patients &Procedures: The study included neonates who had a birth weight (BW) of 1-1.8 kg, a gestational age (GA) of full 28-34 weeks, and a postnatal age of ≤ 96 hours. A blinded, randomized, placebo-controlled study was done using two groups; one of them received bovine colostrum daily within the first 96 hours starting from the 2nd day of feeding and for …

Age-Related Ultrastructural Differences In The Dorsal Cortex Of The Inferior Colliculus In The Fischer Brown Norway Rat, Kylee M. Tenney, Dakota Smallridge, Gillian Barach, Gurveer Singh, Erin Beskitt, Justine Busby, Syllissa Duncan, Alexa Wawrzyniak, Brenda Vega, Nick Tokar, Andrew Ohl, Jesse Young, Jeffrey Mellott

Williams Honors College, Honors Research Projects

The inferior colliculus is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC. The ICd is a non-lemniscal nucleus that is well …

Bodies Of Knowledge: The Accuracy Of Medical Anatomical Drawings From The 14th To The 18th Century, Marina G. Mitchell

Honors Undergraduate Theses

From the fourteenth to the eighteenth centuries, European anatomical illustration underwent major transformations in response to changing scientific methods, technologies, and visual conventions, reflecting critical transitions in anatomical history. Scientific evolution allowed these images to achieve increasing structural precision and internal detail, though they frequently diverged from anatomical forms as they are understood today. This study examines how anatomical inaccuracies across five centuries emerged not from ignorance, but from deliberate mediation between purpose, observation, pedagogy, artistic convention, and cultural ideology. Through close analysis of works in visual comparison to their modern counterparts, this thesis identifies specific deviations from the twenty-first …

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 …

Analyzing Early Medieval Perspectives Of Fetal Development, Nivedha Srinivasan

Honors Undergraduate Theses

This thesis examines early medieval perspectives of fetal development by analyzing two manuscripts: British Library, Cotton Tiberius A III and Leiden University, Vossianus lat. Q69. This study will investigate how knowledge of pregnancy was shared throughout England before the establishment of universities. Interest in medieval reproductive language has piqued in importance in recent years, especially due to modern legal debates surrounding reproductive rights. By examining descriptions of the nine months of fetal development in these two manuscripts, as well as in widely known earlier medical texts like Pliny’s Natural History and Vindicianus’ Gynaecia, this research explores how monastic writers in …

Evaluating The Efficacy And Safety Of Inactivated Dengue Vaccines In Vulnerable Populations, Alaa Daghash

Honors Undergraduate Theses

Dengue virus is a mosquito-borne flavivirus responsible for over 390 million annual cases worldwide. While there are live-attenuated vaccines available to prevent dengue, none are currently approved for use in the United States, and existing platforms pose significant risks of viral reactivation and antibody-dependent enhancement in vulnerable populations, such as pregnant women, children under the age of nine, and the immunocompromised. This widespread exclusion of vulnerable populations exposes a significant vaccine equity gap in dengue prevention, as the populations most at risk for severe dengue are the same ones who are currently excluded from vaccination. In this study, I conducted …

Post-Metabolites Of Two Commensal Bacteria Suppress Dna Damage In An Experimental Model Of Acid Reflux Disease, Maanya Pradeep

Honors Undergraduate Theses

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality …

The Role Of P2y1 And P2y2 Receptors In Human Neural Stem Cell Proliferation, Daria Sokolova

Honors Undergraduate Theses

Endogenous neural stem cells (NSCs) are located in specialized niches of the adult brain and play a vital role in both neurogenesis and neuronal repair. However, declines in NSC proliferation and metabolism associated with age and pathology make these cells less efficient at responding to neurodegenerative disease. Understanding signaling pathways that regulate NSC function is therefore essential for the understanding and development of treatments for these conditions. P2Y receptors are G-protein-coupled purinergic receptors that are activated by extracellular nucleotides and regulate cellular metabolism and proliferation. Among the eight known P2Y subtypes, P2Y1 and P2Y2 have been linked to neuronal signaling …

Effect Of Plant-Based Vs. Standard American Diet On Cardiovascular Parameters In College Students, Timothy J. Horanic

Honors Undergraduate Theses

This study examines how adherence to different dietary patterns—specifically a plant-based diet compared to the standard American diet—can influence physiological indicators tied to cardiovascular health, including heart rate variability (HRV), blood pressure (BP), and heart rate (HR). Among these markers, HRV is considered especially sensitive to autonomic nervous system (ANS) regulation and may offer earlier insight into physiological stress or dysfunction than HR or BP alone. Although nutritional habits are widely believed to impact heart health, few investigations have focused on how specific long-term diets affect autonomic and cardiovascular metrics in healthy, college-aged adults. This study aims to investigate if …

Overcoming Radiation Resistance: Ferroptosis Induction To Sensitize Solid Tumors To Radiation Therapy, Joseph Carmicheal, Caden M. Fritson, Alexandra Seas, Heidi M. Vieira, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

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, …

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 …

Ultra-Processed Foods And The Cardiovascular-Kidney-Metabolic Continuum: Integrating Epidemiological, Multi-Omics, And Translational Evidence, Saiful Singar, Amirhossein Ataei Kachouei, Leandro Lantigua-Somoano, David Manley, Anthony Cardinale, Muhammad Zulfiqah Sadikan, Saurabh Kadyan, Donya Shahamati, Lorena Dias, Amber Wood, Cinthia Chavarria, Sara K. Rosenkranz, Neda S. Akhavan

Department of Medicine Faculty Publications

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently …

Cb1 Allosteric Modulation: Preclinical Insights Into Therapeutic Potential And Misuse Liability, Mohammed A. Mustafa

Theses and Dissertations

Cannabinoid type-1 (CB1) allosteric modulators represent a promising approach to modulate CB1 receptor signaling by binding to distinct receptor sites, without producing adverse cannabimimetic and dependence-related effects associated with Δ9-tetrahydrocannabinol (THC) and other CB1 agonists. This dissertation investigates the pharmacological, behavioral, and dependence-related profiles of CB1 allosteric modulators for their therapeutic potential and misuse liability. Presented here, the chiral CB1 positive allosteric modulator (PAM) ZCZ011 was resolved into its R- and S-enantiomers and characterized across in vitro and in vivo assays. Both enantiomers enhance CB1 agonist activity and produce intrinsic effects in vitro. Behaviorally, they produce antinociceptive effects in the …

Targeting Nuclear Receptors In Muscular Dystrophies And Regenerative Myogenesis, Eira Mann, Hoang Vu, Vihang A Narkar, Yu Liu

The Brown Foundation: Institute of Molecular Medicine

Skeletal muscle is a highly plastic tissue with a robust capacity for regeneration, largely driven by resident satellite cells. Muscular dystrophies comprise a heterogeneous group of inherited disorders characterized by progressive muscle degeneration, chronic inflammation, and impaired regenerative capacity. Despite well-defined genetic etiologies, effective disease-modifying therapies for these disorders, as well as many acquired myopathies, remain limited. Emerging evidence identifies nuclear receptors (NRs) as key regulators of skeletal muscle homeostasis, integrating hormonal, metabolic, and environmental signals to control transcriptional programs governing mitochondrial function, metabolism, inflammation, and myogenesis. In this review, we summarize the diverse roles and mechanisms of action of …

Immune Checkpoint Inhibitor-Induced Cardiotoxicity: From Immune Mechanisms To Clinical Surveillance And Targeted Therapies, Nathan K Chen, Kathryn D Hok, Narsi Chokshi, Anthony Shadid, Haydn E Rich, Lavanya Gunamalai, Marie-Francoise Doursout, Nirmal K Banda, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across a broad range of malignancies by restoring antitumor immunity through blockade of key inhibitory immune pathways, including programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Yet the same widespread immune activation that drives their therapeutic benefit renders patients susceptible to immune-related adverse events (irAEs). Among these cardiovascular toxicities have emerged as a particularly critical concern, drawing growing attention within the evolving field of cardio-oncology. ICI-associated cardiotoxicity encompasses a broad clinical spectrum, ranging from myocarditis and pericarditis to arrhythmias, heart failure, and vascular complications. Of these, …

A Complete Diploid Human Genome Benchmark For Personalized Genomics, Nancy F. Hansen, Nathan Dwarshuis, Hyun Joo Ji, Arang Rhie, Hailey Loucks, Glennis A. Logsdon, Mitchell R. Vallger, Jessica M. Storer, Juhyun Kim, Eleni Adam, Nicolas Alternose, Dmitry Antipov, Mobin Asri, Sofia Barreira, Stephanie C. Bohaczuk, Andrey V. Bzikadze, Sara A. Carioscia, Andrew Carroll, Kuan-Hao Chao, Yanan Chu, Arun Das, Peter Ebert, Adam English, Mark Fleharty, Laura E. Fleming, Giulio Formenti, Andrea Guarracino, Gabrielle A. Hartley, Katharine Jenike, Jenna Kalleberg, Yu Kang, Robert King, Josipa Lipovac, Mira Mastoras, Matthew W. Mitchell, Shloka Negi, Nathan D. Olson, Keisuke K. Oshima, Luis F. Paulin, Brandon D. Pickett, David Porubsky, Jane Ranchalis, Desh Ranjan, Mikko Rautiainen, Harold Riethman, Robert D. Schnabel, Fritz J. Sedlazeck, Kishwar Shafin, Mile Sikic, Steven J. Solar, Alexander P. Sweeten, Winston Timp, Justin Wagner, Dongahn Yoo, Ying Zhou, Erik Garrison, Evan E. Eichler, Michaeel C. Schatz, Andrew B. Stergachis, Rachel J. O'Neill, Karen H. Miga, Steven L. Salzberg, Sergey Koren, Justin M. Zook, Adam M. Phillippy

School of Medical Diagnostics & Translational Sciences Publications

Human genome sequencing typically relies on mapping reads to a reference genome to call variants, but this approach introduces technical biases, excluding duplicated and structurally polymorphic regions of the genome. To overcome this, we present a telomere-to-telomere genome benchmark with near-perfect accuracy across 99.4% of the diploid HG002 genome. This benchmark adds 701.4 Mb of autosomal sequence and both sex chromosomes (216.8 Mb), which were absent from prior benchmarks. We annotated genes and repeats on both haplotypes, including 19,956 protein-coding genes on the maternal haplotype and 19,190 on the paternal haplotype, and developed new methods to measure the accuracy of …