Medicine and Health Sciences Commons^™

Fusion: A Web-Based Application For In-Depth Exploration Of Multi-Omics Data With Brightfield Histology, Samuel P Border, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, …

Evolutionary Loss Of An Antibiotic Efflux Pump Increases Pseudomonas Aeruginosa Quorum Sensing Mediated Virulence In Vivo, Sheryl E Fernandes, Humberto Ortega, Mylene Vaillancourt, Anna Clara M Galdino, Aleksandr Stotland, Kyu Shik Mun, Diane Aguilar, Yohei Doi, Janet S Lee, Elizabeth B Burgener, Jeffrey E Barrick, Jeffrey W Schertzer, Peter Jorth

2020-Current year OA Pubs

Antibiotic resistance is a threat to human health, yet recent work highlights how loss of resistance may drive pathogenesis in some bacteria. In two recent studies, we found that β-lactam antibiotics and nutrient stresses faced during infection selected for genetic inactivation of the Pseudomonas aeruginosa antibiotic efflux pump mexEFoprN. Unexpectedly, efflux pump mutations increased P. aeruginosa virulence during infection; however, neither the prevalence of mexEFoprN inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants are known. We hypothesized that human infection would select for virulence enhancing mutations. Using genome sequencing of clinical isolates, …

Health And Climate At Cop29: Advancing Integration And Bridging Research Gaps, Rupa R Patel, Yevheniia Varyvoda, Hiba Baroud, Philip J Landrigan, Aminata Kilungo

2020-Current year OA Pubs

Climate and health science is a rapidly growing, interdisciplinary field and holds importance during intergovernmental climate adaptation and mitigation policy negotiations. The 29th session of the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) convened stakeholders for negotiations and scientific discourse. This viewpoint presents insights gained by the authors' participation at COP29 focused on health and climate. The authors analyze the evolving integration of health into the UNFCCC process, dissect the contributions and the role of the Research and Independent Non‑Governmental Organizations (RINGOs), a constituency to achieve this endeavor, and identify the key …

Breaking The Silence: A Scoping Literature Review On Trauma-Informed Care For Black Women Navigating Sexual Health-Related Trauma, Ayanna Troutman, Funlola Are, Ashley Okoye, Sarah Chiang, Destiny Craig, Anthony Akande, Irene Stafford

Faculty, Staff and Student Publications

Black women disproportionately experience sexual health-related trauma, yet their mental health needs are often inadequately addressed due to systemic barriers and stigma. This literature review examines trauma-informed care (TIC) frameworks tailored to Black women, emphasizing culturally responsive practices in addressing sexual health-related trauma. By synthesizing findings from existing research, including the importance of intersectionality, culturally specific interventions, and community-centered approaches, this review highlights effective strategies for mental health providers. The review concludes with implications for enhancing TIC training and implementation in clinical settings which contributes to the advancement of equitable mental health services for Black women.

Use Of Simulation For Teaching Biomedical Sciences To Undergraduate Medical Students- A Scoping Review., Joshua Owolabi, Katresa Gardner, Rasheed Agboola, Rekha Yesudas, Jennifer H. Shaw

PCOM Scholarly Works

INTRODUCTION: The objective of this scoping review was to understand the methods, extent and type of evidence in relation to the use of simulation or SIM-based medical education pedagogies to teach biomedical sciences to undergraduate medical students in accredited medical schools, globally. The review considers literature published between 2014 and 2024.

INCLUSION CRITERIA: The review only considered reports about populations of students enrolled in accredited undergraduate medical education programs that train medical doctors, including DO/MD/MBBS/MBChB or equivalents in any country. Simulation, as a concept, is considered as reportedly used in the context of teaching knowledge, skills, or practice-related attitudes in …

Examining Factors Influencing Ultra- Processed Food Consumption Among Liberty University Students Aged 18 And Older, Ginika Rosemary Muomah

Masters Theses

Ultra-processed foods (UPFs) are widely consumed among college students and are linked to adverse health outcomes including obesity, poor mental health, and cardiometabolic disease. Despite their rising prevalence, limited research has examined psychosocial and behavioral factors influencing UPF intake within Christian university settings. This study investigated demographic, behavioral, and psychosocial predictors of UPF consumption among Liberty University students, guided by the Health Belief Model (HBM). A cross-sectional survey of students aged 18 and older (N = 337) was conducted. After excluding incomplete or invalid responses, 276 cases remained. The 25-item survey assessed UPF intake, HBM constructs, and demographics. Descriptive statistics …

Toward A Clinically Actionable, Electronic Health Record-Based Machine Learning Model To Forecast 90-Day Change In Hemoglobin A1c In Youth With Type 1 Diabetes: Feasibility And Model Development Study, Erin M. Tallon, David D. Williams, Cintya Schweisberger, Colin Mullaney, Brent Lockee, Diana Ferro, Craig Vandervelden, Mitchell S. Barnes, Angelica Cristello Sarteau, Anna R. Kahkoska, Susana R. Patton, Sanjeev Mehta, Ryan Mcdonough, Marcus Lind, Leonard D'Avolio, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinicians currently lack an effective means for identifying youth with type 1 diabetes (T1D) who are at risk for experiencing glycemic deterioration between diabetes clinic visits. As a result, their ability to identify youth who may optimally benefit from targeted interventions designed to address rising glycemic levels is limited. Although electronic health records (EHR)-based risk predictions have been used to forecast health outcomes in T1D, no study has investigated the potential for using EHR data to identify youth with T1D who will experience a clinically significant rise in glycated hemoglobin (HbA1c) ≥0.3% (approximately 3 mmol/mol) between diabetes clinic visits. …

The Relationship Between Nursing Faculty Sense Of Belonging And Faculty Intent To Stay, Heather M. Bowers

Doctoral Dissertations and Projects

The purpose of this quantitative causal-comparative and correlational study was to evaluate the relationship between workplace sense of belonging and intent to stay in the current nursing faculty role among full-time nursing faculty. The shortage of nursing faculty impacts the ability to prepare the next generation of nurses needed to meet worldwide nursing demands. Strategies to effectively recruit and retain nursing faculty are important considering the current shortage and increasing retirements of nursing faculty. While sense of belonging has been studied for student retention and studies are beginning to explore the importance of workplace belonging, the impact of organizational sense …

Cardiovascular Disease In Rural Communities: Understanding The Challenges And Solutions – A Comparative Approach, Aariyana R. Britton

Doctoral Dissertations and Projects

This research project explored the effects of cardiovascular disease (CVD) in rural and underrepresented populations while solidifying ways of mitigation in localities with little to no healthcare access. Research included highly underserved individuals who live in or around healthcare deserts with low health literacy statuses and poor resource distribution. CVD has skyrocketed into becoming the leading cause of death in the United States of America, so it is pertinent to create methods of investigation regarding how CVD is currently diagnosed, handled, and projected in these areas where there is a shortage of proper health access and training. While CVD is …

Non-Opioid Alternatives For Chronic Non-Cancer Pain Management In The Elderly: A Provider’S Perspective, Okey Iloegbunam

Doctoral Dissertations and Projects

Chronic non-cancer pain is a major public health problem in the United States. The use of opioids for chronic non-cancer pain treatment has a negative impact on the quality of life of the elderly. This study aimed to explore non-opioid alternatives for chronic pain management in the elderly. It aims to explore the perspectives of pain practitioners at My Pain Center in Tucson, Arizona, in choosing non-opioid alternatives for chronic pain treatment. The study aimed to explore the factors that influence pain practitioners’ prescribing habits and how to replace opioids in treating chronic non-cancer pain in the elderly. This study …

Bridging The Gap: Does Individual Crossfit Open Performance & Event-Type Influence Crossfit Games Team Performance?, Anthony J. Mack

Doctoral Dissertations and Projects

Individual CrossFit Open (CFO) and CrossFit Games (CFG) performance factors, including physiological metrics, sex, competitive experience, and workout pacing strategies, are well established; however, there is a gap in the literature comparing CFO and CFG team performance. The purpose of this study was to examine whether individual CFO scores and event category (i.e., monostructural, gymnastics-skill, weightlifting, or work capacity) influence a team's final score at the CFG. Teams (n = 196) from the 2018-2024 CFG seasons were included in data collection. Data from CFO workouts (n = 28) and CFG team events (n = 62) were extracted from games.crossfit.com. Scores …

The Lived Experiences Of Micu Nurses During The Covid-19 Pandemic: A Qualitative Study, Thomas Hopkins

Doctoral Dissertations and Projects

The purpose of this phenomenological study was to explore the lived experiences of MICU nurses during the COVID-19 pandemic and how these experiences may inform disaster preparedness in the nursing curriculum. This research is guided by Watson’s (1979) theory of human caring. The theory emphasizes the importance of interpersonal relationships and emotional support in nursing practice, and how these elements can be integrated into disaster preparedness training. Using interpretive phenomenological analysis, data were collected through semi-structured interviews, field notes, and guided journaling. The interviews were conducted via digital conferencing software over the internet. Field notes were recorded during the interviews. …

Approach To Ophthalmic Surgery Involving The Anterior Vitreous: A Clinical Practice Update From The American Society Of Retina Specialists, Matthew R Starr, Christina Y Weng, Lejla Vajzovic, Kevin J Blinder, Judy E Kim, J Michael Jumper

Faculty, Staff and Students Publications

When encountering diseases of the anterior vitreous and peripheral retina (ie, the "middle segment" of the eye), vitreoretinal (VR) surgeons are specifically trained in surgical techniques for managing the vitreous and visualizing the peripheral retina during anterior vitrectomy, and therefore they are well equipped to address the complications of surgery involving the anterior vitreous space. This clinical update reviews and compares the current literature discussing techniques and patient outcomes related to complete pars plana vitrectomy versus incomplete, subtotal pars plana vitrectomy, and addresses the proposition of developing an abridged training curriculum for non-VR surgeons to acquire the knowledge and skills …

Smarcal1 Is A New Osteosarcoma Predisposition Gene, Maryam Rafati, Lillian M Guenther, Laura E Egolf, D Matthew Gianferante, Jung Kim, Kevin Wang, Bin Zhu, Logan G Spector, Nathan Anderson, Katherine A Janeway, Donald A Barkauskas, Douglas S Hawkins, Ana Patiño-Garcia, Philip J Lupo, Michael E Scheurer, Lindsay Morton, Gregory T Armstrong, Yadav Sapkota, M Monica Gramatges, Massimo Serra, Claudia Hattinger, Katia Scotlandi, Irene L Andrulis, Jay S Wunder, Mandy L Ballinger, David M Thomas, Meredith Yeager, Michael Dean, Douglas R Stewart, Aurelie Vogt, Jia Liu, Belynda D Hicks, Wen-Yi Huang, Maria Teresa Landi, Adriana Lori, W Ryan Diver, Sharon A Savage, Stephen J Chanock, Lisa Mirabello

Faculty, Staff and Students Publications

Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most cases are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2,119 osteosarcoma cases, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across three osteosarcoma case sets (1.8%, n = 2,119) than in 2,625 comparably sequenced cancer-free controls (0.3%; P <  .001). Cases with SMARCAL1 pathogenic variants had significantly improved overall survival compared to cases without these variants (hazard ratio 0.36, 95% CI 0.14-0.96, P = .034). In the UK Biobank (469,557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.

Lysosomes Signal Through The Epigenome To Regulate Longevity Across Generations, Qinghao Zhang, Weiwei Dang, Meng C Wang

Faculty, Staff and Students Publications

The epigenome is sensitive to metabolic inputs and crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We find that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic-target-of-rapamycin (mTOR) signaling increased expression of a histone H3.3 variant and increased its methylation on K79, leading to lifespan extension across multiple generations. This transgenerational pro-longevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase, and was recapitulated by …

Postsurgical Pain, Psychosocial Functioning, And Cannabis Use Among Adolescents And Young Adults Undergoing Gender Affirming Surgery, Eleanor Battison, Emily A. Kenyon, Corrin Murphy, Eline Lenne, Danielle N. Moyer, Sarah W. Feldstein Ewing, Anna C. Wilson

School of Social Work Faculty Publications and Presentations

Purpose: Little is known about transgender and gender expansive (TGE) adolescents and young adults (AYAs) pain and psychosocial experiences in the acute postsurgical period following gender-affirming surgery (GAS). This study describes pain symptomatology and psychosocial functioning within 1 month after GAS among TGE AYAs, examines immediate postsurgical associations of cannabis use with pain symptomatology, pain catastrophizing, and psychosocial functioning, and explores pain persistence, cannabis use, and psychosocial functioning in a subgroup of individuals 6 months after surgery.

Methods: AYAs (N = 64) underwent GAS at a large academic medical center in the Pacific Northwest between March 2019 and June …

Swollen Lymph Node Metastasis In Gastric Cancer: A Forgotten Prognostic Signal In Need Of Clinical Action, Keykavous Parang, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Gastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the …

Enhancing Patient Understanding And Reducing Readmissions: Implementing A Structured Discharge Teaching Protocol In A Medical-Surgical Unit, Jawany Joseph

DNP Projects

Background

Hospital readmissions remain a critical challenge in healthcare, especially in medical-surgical units. The high rates of hospital readmissions are often linked to inadequate patient understanding of discharge instructions. Many patients struggle with deciphering discharge plans, leading to medication errors, missed follow-up appointments, and poor self-care management. A structured discharge teaching protocol has the potential to enhance patient comprehension, improve adherence to port-discharge care, and reduce readmission rates.

Project Goals

This project aimed to improve understanding of discharge instructions, reduce hospital readmissions, and enhance patient satisfaction with the discharge process. Specific objectives included increasing patient comprehension from 65% to 90% …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

Purulent Pericarditis: Treating A Medically-Complex Patient With Intrapericardial Antibiotics, Meryem Guler, Sudheshna Vemula, Matthew Hart, Josh Wiener, Darius Farzad, Mark Decaro, Gregary D. Marhefka, Devin Weber, John W.C. Entwistle, Jacqueline Urtecho

Division of Cardiology Faculty Papers

OBJECTIVE: Purulent pericarditis is a rare, lethal complication of a bacterial pericardial infection. This case report outlines the protocol for instilling intrapericardial antibiotics for methicillin-sensitive Staphylococcus aureus (MSSA) pericarditis without fibrinolytics in a 51-year-old man.

KEY STEPS: An appropriately sized percutaneous pericardial drain was placed. Then, a 3-day course of intrapericardial infusions of 50 mL vancomycin was begun. Drainage of all accessible fluid was performed before each infusion. The daily infusions each had an 8-hour dwell time. The prior drainage protocol continued after each infusion.

POTENTIAL PITFALLS: Strict dosage and infusion length management are required to prevent direct toxicity. Potential …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

Comparing Ideology And Covid-19 Preferences Of Canadian Public Health Workers And The General Population, Simon Kiss, Patrick Fafard, Andrea Perrella, Ketan Shankardass, Erick Lachapelle, Matthew Arp, Joslyn Trowbridge

Laurier Institute for the Study of Public Opinion and Policy

Objectives: This study tests whether and how the Canadian public health workforce differed from the Canadian general population in their political attitudes, worldviews and policy preferences related to the COVID-19 pandemic.

Methods: Nearly identical surveys were fielded to the Canadian public health workforce in 2021 through leading public health associations and to a census-balanced sample of the general Canadian population in February and March 2021. through a consumer quota sample for a survey of the general population.

Results: The Canadian public health workforce demonstrates systematically more left-wing pro-egalitarian, anti-hierarchical, anti-individualist worldviews. Those in health promotion positions are slightly more to …

Physical Activity, Screen Time, Dietary Habits, And Health Outcomes Among Children And Adolescents In The Middle East And North Africa Region: A Narrative Review, Shaikha Eisa Alnaqbi, Rahab Sohail, Hadia M. Radwan, Maysm N. Mohamad, Falak Zeb, Haydar Hasan, Mona Hashim, Tareq Osaili, Sharifa Alblooshi, Ayesha S. Al Dhaheri, Lily Stojanovska, Leila Cheikh Ismail

All Works

Background/objectives: Fat mass and obesity associated (FTO) gene and anthropometric measurements might be associated with breast cancer (BC) risk. This study aimed to assess the interactions between single nucleotide polymorphism (SNP) rs9939609 of the FTO gene, anthropometric indices, and BC risk among pre- and post-menopause women with overweight/obesity in Pakistan. Methods: This retrospective case–control study conducted on a convenience sample of 200 women divided into two groups: a case group comprised of 100 women diagnosed with BC, and control group comprised of 100 (age and menopausal status matched healthy women). Physical activity was assessed using validated questionnaire. Data on body …

Dental Microwear And Diets Of Late Miocene Primates From Rudabánya, Hungary, Peter S. Ungar, Anna K. Wilcox, David R. Begun

School of Dentistry Faculty Publications

Objectives: This study focuses on a dental microwear texture analysis of European pliopithecids and dryopithecins from the Miocene primate site of Rudabánya, Hungary. The goal is to determine whether these taxa, found in part together in the same deposits, differed in their food preferences, or at least consumed, on a daily basis, in a manner that might have facilitated sympatry. Materials and Methods: Here we report on a molar surface texture analysis of all available fossil primates from Rudabánya that preserve antemortem microwear. This includes both Anapithecus hernyaki (n = 14) and Rudapithecus hungaricus (n = 5, including one from …

Global, Regional, And National Burden Of Cardiovascular Diseases And Risk Factors In 204 Countries And Territories, 1990-2023, Global Burden Of Cardiovascular Diseases And Risks 2023 Collaborators, Mohammadreza Abbasian

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging.

OBJECTIVES: We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure.

METHODS: The Global Burden of Disease (GBD) 2023 study, a multinational …

Refractory Cutaneous Symptoms In Systemic Mastocytosis, Laura Gleason, Safiyyah Bhatti, Molly Wallace, Jason B. Lee, Onder Alpdogan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Association Of Genetic Scores Related To Insulin Resistance With Neurological Outcomes In Ancestrally Diverse Cohorts From The Trans-Omics For Precision Medicine (Topmed) Program, Chloé Sarnowski, Yixin Zhang, Farah Ammous, Lincoln M P Shade, Daniel Dicorpo, Xueqiu Jian, Donna K Arnett, Thomas R Austin, Alexa Beiser, Joshua C Bis, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Charles S Decarli, Harsha Doddapaneni, Josée Dupuis, David W Fardo, Jose C Florez, Stacey Gabriel, Richard A Gibbs, David C Glahn, Namrata Gupta, Hector M González, Kevin A González, Konstantinos Hatzikotoulas, Kathleen M Hayden, Susan R Heckbert, Bertha Hidalgo, Alicia Huerta-Chagoya, Timothy M Hughes, Sharon L R Kardia, Charles L Kooperberg, Lenore J Launer, W T Longstreth, Ravi Mandla, Rasika A Mathias, Andrew P Morris, Thomas H Mosley, Ilya M Nasrallah, Paul Nyquist, Bruce M Psaty, Qibin Qi, Laura M Raffield, Nigel W Rayner, Alexander P Reiner, Claudia L Satizabal, Elizabeth Selvin, Magdalena D R Sevilla-Gonzalez, Albert V Smith, Jennifer A Smith, Kirk Smith, Beverly M Snively, Lorraine Southam, Tamar Sofer, Ken Suzuki, Henry J Taylor, Miriam S Udler, Karine A Viaud-Martinez, Sylvia Wassertheil-Smoller, Alexis C Wood, Lisa R Yanek, Xianyong Yin, Alisa K Manning, Jerome I Rotter, Stephen S Rich, James B Meigs, Myriam Fornage, Sudha Seshadri, Alanna C Morrison, Topmed Neurocognitive Working Group, Topmed Diabetes Working Group

The Brown Foundation: Institute of Molecular Medicine

To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P <  0.002) of the cross-population (P = 1.3 × 10-5) and European (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P <  0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells In The Aging Kidney: Secondary Results Of A Parkinson’S Disease Clinical Trial, Juan D Martinez-Lemus, Donald A Molony, Jessika Suescun, Emily Tharp, Tia S Thomas, Charles Green, Chiamaka Onuigbo, Robert Ritter, Mya C Schiess

Faculty, Staff and Student Publications

Background: Kidney function declines with age, largely due to chronic low-grade inflammation. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory effects in certain immune-mediated kidney diseases, but their role in preserving renal function in aging individuals without chronic kidney disease (CKD) remains unclear. This study presents secondary outcome findings from a randomized clinical trial in Parkinson's disease (PD), evaluating the impact of allogeneic human bone marrow-derived MSCs (allo-hMSCs) on kidney function in an aging population with PD with preserved renal function.

Methods: Subjects with PD aged 50-79 years with baseline estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 were randomized to …

Associations Between Adhering To 24-Hour Movement Guidelines And Anxiety Among Adolescents Across Intersectional Identities: Kyrbs 2020-2022., Suryeon Ryu, Eun Young Lee, Zan Gao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Identifying preventive measures for adolescent mental health is a global public health priority, as poor mental health heightens the risk of early death from related issues, including suicide. This study examined the associations between adherence to the 24-Hour Movement Guidelines and anxiety among a nationally representative sample of South Korean adolescents, using an intersectional identity framework.

METHODS: Data from the 2020-2022 Korea Youth Risk Behavior Surveys were analyzed. Adolescents aged 12-17 years were grouped based on adherence to guidelines: none, physical activity (PA), sedentary behavior (SB), sleep, two guideline combinations, and all three. Anxiety was the mental health outcome. …