Digital Commons Network^™

The Influence Of Adverse Childhood Experiences On Female Violent Offending: A Scoping Systematic Review, Alexis M. Wolgemuth

Theses, Dissertations and Capstones

Female-perpetrated violence has exhibited concerning data trends in recent years. Prior scholarship indicates that past victimization and trauma in childhood, known as adverse childhood experiences (ACEs), are highly prevalent among women offenders. However, the research concerning ACEs and violent females is scattered. This thesis provides a scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) updated 2020 guidelines. A systematic database search was conducted using Academic Search Complete, SAGE Journals, Springer Nature Link, and HeinOnline to identify relevant peer-reviewed journal articles. Inclusion and exclusion criteria are established, focusing on studies published after January 2015. These …

Role Of Estrogen Receptor Alpha In Modulating The Circadian System In Female Mice, Victoria Alvord

Theses and Dissertations--Biology

Circadian rhythms are approximately 24-hour cycles of physiology and behavior. Circadian rhythms of eating, or meal timing, are linked to cardiometabolic dysfunction in humans. Mistimed eating, such as breakfast skipping and eating late at night, increases the risk of obesity, diabetes, and cardiovascular disease in humans. Likewise, disrupted eating rhythms cause obesity in mice. This dissertation investigates how estrogens regulate eating behavior rhythms and tissue clock timing in female mice. Chapter 1 reviews three key components critical to this work. The first is an overview of the field of chronobiology and the function of the circadian system. The second is …

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 …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

A Microenvironment-Driven Hla-Ii-Associated Insulin Neoantigen Elicits Persistent Memory T Cell Activation In Diabetes, Neetu Srivastava, Anthony N Vomund, Rongzhen Yu, Orion J Peterson, Yuqing Yang, David P Turicek, Omar Abousaway, Tiandao Li, Pamela Stone, Aisha Ansar, Rima Melhem, Bo Zhang, Chang Liu, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Emil R Unanue, Ana Maria Arbelaez, Cheryl F Lichti, Xiaoxiao Wan, Et Al.

2020-Current year OA Pubs

The antigenic landscape of autoimmune diabetes reflects a failure to preserve self-tolerance, yet how novel neoantigens emerge in humans remains incompletely understood. Here we designed an immunopeptidomics-based approach to probe HLA-II-bound, islet-derived neoepitopes in patients with type 1 diabetes. We uncovered a Cys→Ser transformation, conserved between mice and humans, that reshapes autoreactivity to insulin at the single-residue level. This transformation, which we call C19S, arises from oxidative remodeling of insulin in stressed pancreatic islets and also occurs in cytokine-activated antigen-presenting cells, contributing to a feed-forward loop of neoepitope formation and presentation. Despite involving just one amino acid, C19S is recognized …

The Underdiagnosis Of Neurodevelopmental Disorders In Women: Recognizing A Spectrum Of Symptoms, Taylor D. Bloomhuff

Psychology Doctoral Specialization Projects

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have long been viewed as predominantly male diagnoses. Based on foundational studies for these disorders, not only are they more prevalent in male children, but symptom severity is also higher in male children. In attention-deficit/hyperactivity disorder in particular, it has become a common assumption that hyperactive/impulsive and combined types are ‘male’ ADHD presentations, while the inattentive type corresponds to the few female children who meet diagnostic criteria. However, emerging research looking at the decrease in autism spectrum disorder and attention-deficit/hyperactivity disorder prevalence rates between gender in adulthood suggests that these neurodevelopmental disorders …

Redrawing Anatomy: Addressing Female Genital Underrepresentation In Educational Texts, Clara E. Krohn

Williams Honors College, Honors Research Projects

The fight for female equality in the historically male dominated medical field is an ongoing battle. This project focuses primarily on the underrepresentation of female genitalia in undergraduate academic textbooks. A dissected pelvis of a female cadaver was initially examined. Pictures were obtained with scale bars to accurately depict size of the structures included. Underrepresented structures such as the clitoris and the broad ligament were closely examined along with the reproductive system as a whole. The pictures compiled along with further research were used to design a portfolio of diagrams and a survey to be later administered. The survey was …

“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 …

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 …

Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …

Proliferation And Apoptosis Adaptor Protein 15 (Pea15), A Potential Oncogenic Regulator Of Vhl And Hif1a Identified Through Proteomic Analysis In Hepatocellular Carcinoma, Yun Seong Jeong, Ji-Hyun Shin, Soo Mi Kim, Bo Hwa Sohn, Sun Young Yim, Ji Hoon Kim, Jae Jun Shim, Sung Hwan Lee, Yun Shin Chun, Sunyoung S Lee, Hui Dai, Ahmed Kaseb, Koo Jeong Kang, Holger K Eltzschig, A Robert Macleod, Xiaolin Luo, Alexey Revenko, Youngsoo Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Digital Communication Strategies For Culinary Medicine In Cancer Prevention And Survivorship: Information-Seeking Habits And Content Preferences Of Online Cooking Media Among Adults Participating In Four Cancer Prevention And Control Cohort Studies, Margaret Raber, Sara Fares, Maria Vazquez, Larkin Strong, Carrie Daniel-Macdougall, Lorna Mcneill, Karen Basen-Engquist

Faculty, Staff and Student Publications

Introduction

Poor diet and excess weight have been linked to increased risk for at least 13 types of cancer. Culinary medicine utilizes experiential cooking skill development to improve individuals’ capacity for healthy eating. Digital communication strategies offer pathways for scalable culinary medicine interventions, but little research has explored how online cooking tools could be leveraged for cancer prevention messaging. We conducted a cross-sectional survey study exploring online cooking information-seeking habits and content preferences among participants in four cancer prevention and control cohorts to inform future digital culinary medicine interventions.

Methods

A cross-sectional survey study was conducted with a convenience sample …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail

Faculty, Staff and Student Publications

Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …

Intratracheal Interleukin-10 Administration Reduces Acute Lung Injury Induced By Sulfur Dioxide Exposure In Mice, Amy J. Nelson, Todd A. Wyatt, Bradley W. Richmond, Belinda Diaz, Angela Gleason, Michael J. Duryee, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of reducing acute high-consequence airborne chemical exposure-induced lung disease are lacking. This study seeks to determine the therapeutic potential of interleukin (IL)-10 administered following acute sulfur dioxide (SO₂) exposure in mice. C57BL/6 male and female mice were exposed to SO₂ gas at 125 ppm for 4 h and subsequently treated 2-3 h later with IL-10 (1 μg) or vehicle control by intratracheal instillation for a total of 3 doses over 2 days with comparisons to sham-treated mice (N = 20 mice/group). IL-10 treatment reduced SO₂-induced weight loss with corresponding reductions in SO_{2 …}

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix …

Prolonged Qt Interval In Hiv-1 Infected Humanized Mice Treated Chronically With Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine, Ali Namvaran, Julian V. Garcia, Mahendran Ramasamy, Kayla Nguyen, Farzaneh Tavakkoli Ghazani, Bryan T. Hackfort, Prasanta Dash, Reagan E. Fisher, Benson J. Edagwa, Santhi Gorantla, Keshoer R. Bidasee

Journal Articles: Cellular & Integrative Physiology

The REPRIEVE Trial recently reported high rates of sudden cardiac death (SCD) middle-aged people living with HIV-1 infection (PWH) using the WHO/NIH-recommended two nucleoside reverse transcriptase inhibitors (NRTIs)/one integrase strand inhibitor (INSTI) regimen to manage HIV-1 viremia. To date, clinically relevant animal models to delineate underlying causes for this remain limited. Here, we assessed if HIV-1-infected NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ humanized mice (Hu-mice) treated with the WHO/NIH-recommended antiretroviral regimen, dolutegravir (DTG, INSTI)/tenofovir disoproxil fumarate (TDF, NRTIs)/emtricitabine (FTC, NRTIs), can recapitulate abnormalities in the ECG and subclinical structural heart disease that serve as harbingers of SCD in middle-aged PWH. …

Noradrenergic Innervation Across Brain Regions Is Altered By Aging And By Disease Progression In A Mouse Model Of Alzheimer’S Disease Neuropathology, Nicole M Hernandez, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Norepinephrine plays critical roles in modulating arousal and attention, is highly dynamic in awake, behaving individuals, and has anti-inflammatory and neuroprotective actions. Notably, the locus coeruleus (LC), the primary source of norepinephrine in the central nervous system, is among the first brain regions to show pathological alterations in early stages of Alzheimer's disease (AD). LC neuronal loss and associated reductions in norepinephrine in the brain have therefore been postulated to play a key role in AD pathophysiology. LC neurons and their axons have been studied in several mouse models of AD-related neuropathology to investigate their contribution to brain dysfunction in …

Common And Recurrent Dysregulated Molecular Network Of Placental Hypoxia And Associated Vasculogenesis And Angiogenesis In Fetal Growth Restriction, Wei Li, Xiaoyi Bai, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes

Host- And Pathogen-Related Determinants Of Pulmonary Versus Extrapulmonary Tuberculosis, Begna Tulu, Thomas Theo Brehm, Reinout Van Crevel, Tobias Dallenga, Andrew R Dinardo, Keertan Dheda, Johanna Eggeling, Wendemagegn Enbiale, Matthias I Gröschel, Jialun Hao, Vinod Kumar, Arjan Van Laarhoven, Rolanda Londt, Gareth Prosser, Philippa Randall, Norbert Reiling, Jan Rybniker, Ulrich E Schaible, Erwin Schurr, Isabelle Suarez, Sebastian J Theobald, Robert J Wilkinson, Christoph Lange

Faculty, Staff and Students Publications

Tuberculosis (TB) primarily manifests as pulmonary TB (PTB), but extrapulmonary TB (EPTB) remains a major clinical challenge. Distinct diagnostic and therapeutic difficulties arise from differences in immune responses, pathogen behaviour and host susceptibility. However, the factors driving disease localisation are still incompletely understood. We conducted a comprehensive narrative review of studies examining differences between PTB and EPTB in terms of epidemiology, mycobacterial factors, genetic and epigenetic determinants, host immune responses, transcriptomic profiles, cytokine and chemokine patterns, and immunophenotypes. EPTB is more common among females, children, older adults and immunocompromised individuals with deficient granuloma formation. This review is intended to provide …

Estrogen Deprivation During Primate (Papio Anubis) Pregnancy: Impact On Systemic Microvascular Flow And Cardiovascular Development And Function After Birth In Offspring, Sifa Turan, Jeffery S. Babischkin, Graham W. Aberdeen, Gerald J. Pepe, Eugene D. Albrecht

Department of Biomedical and Translational Sciences Faculty Publications

Background

Suppressing estradiol (E₂) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E₂ deprivation also impairs microvascular flow and cardiac function.

Methods

Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E₂ (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance.

Results

Letrozole reduced maternal serum E₂ by 95% (p <  0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p <  0.02), replenishment was 5 s slower (p <  0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E₂. Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged.

Conclusion

Prolonged gestational E₂ deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E₂ prevents this, supporting E₂'s role in …

Inhibition Of Histone Demethylase Lsd1 Suppresses Cd47 Expression And Enhances Efficacy Of Cd47 Blockade In Breast Cancer, Fengjie Jiang, Yu Shen, Bing Li, Michael Henry, Nancy Davidson, Yi Huang

Department of Biomedical and Translational Sciences Faculty Publications

Background CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.

Methods We investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using in silico datasets, isogenic cell lines, conditional BRCA1 knockout models, and syngeneic mouse models. Techniques such as immunohistochemistry, multiplex immunofluorescence, immunoprecipitation, protein ubiquitination, chromatin immunoprecipitation, chemotaxis, flow cytometry, and phagocytosis assays were employed to examine the epigenetic regulation of CD47 by LSD1 and …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Surface Marker Identification To Capture Live Circulating Tumor Cells In Metastatic Triple-Negative Breast Cancer, Bree M Lege, Khushali J Patel, Brendan Panici, Ping Gong, Michael T Lewis, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies. Circulating tumor cells (CTC) are invaluable for monitoring metastatic tumor progression and treatment response but are difficult to capture because of their rarity and heterogeneity. Surface-based staining for live CTCs is essential to preserve RNA quality in single cells, but current markers tend to perform poorly on more mesenchymal tumor cells such as TNBCs. To enhance live TNBC CTC detection, we developed a workflow for live CTC capture and single-cell RNA sequencing (scRNA-seq). Using a mouse model of metastatic TNBC, we identified four new CTC surface markers, AHNAK2, …

Survodutide For Treatment Of Obesity: Baseline Characteristics Of Participants In A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (Synchronize™-1), Carel W Le Roux, Sean Wharton, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Materials and methods: Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 …

Wnt4 Deficiency Impacts Heart, Diaphragm, And Palate Development: Insights From Human Genetics, Machine Learning, And Mouse Models, Andrés Hernández-García, Bum Jun Kim, David Chitayat, Patrick Shannon, Stephanie Hedges, Maria Al Bandari, Maria J Guillen Sacoto, Emily Anne Bates, Yunus H Ozekin, Victor Faundes, Pamela N Luna, Chad A Shaw, Tara L Rasmussen, Chih-Wei Hsu, Daryl A Scott

Faculty, Staff and Students Publications

WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …