Medicine and Health Sciences Commons^™

Impact Of Trisomy 21 On Post Pull-Through Enterocolitis And Bowel Function In Children With Hirschsprung Disease: A Pcplc Analysis., Marshall W. Wallace, Scott S. Short, Rachel C. Crady, Ron W. Reeder, Hira Ahmad, Kelly Austin, Andrea Badillo, Casey M. Calkins, Megan M. Durham, Julie R. Fuchs, Christopher Gayer, Julia E. Grabowski, Jamie C. Harris, Charles R. Hong, Ankur Rana, Rebecca M. Rentea, Nelson Rosen, Payam Saadai, Caitlin A. Smith, K Elizabeth Speck, Cristine S. Velazco, Richard J. Wood, Michael D. Rollins

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: We evaluated whether Trisomy 21 (T21) affected bowel management use, ability to toilet train for stool, and rates of Hirschsprung-Associated Enterocolitis (HAEC) in children with Hirschsprung disease (HD). We hypothesized that T21 would be associated with increased rates of HAEC, bowel management program (BMP) use, and delayed toilet training for stool.

METHODS: Children with HD in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) database who underwent primary pull-through were included and stratified by T21 status: HD only versus HD + T21. Children requiring a redo pull-through, initially managed with a stoma, or those who had inadequate follow-up were …

A Replication Study - Mental Health And Suicide Risk Among High School Students And Protective Factors — Youth Risk Behavior Survey, United States, 2023, Hannah Baiyor

Capstone Experience: Master of Public Health

The original study (Verlenden et al., 2024) aims to analyze how various protective factors may buffer poor mental health and suicide risk outcomes among US students in grades 9-12, an important public health topic as suicide is one of the leading causes of death among US teens (Centers for Disease Control and Prevention, 2024a). Through studying these associations, this study aims to uncover pathways to positive mental health outcomes and reduced suicide risk. The study utilizes the 2023 YRBS dataset, a nationally representative sample of US public and private school students in grades 9-12, to estimate prevalence of four mental …

Hope Kit Program, Monica Reuber

Capstone Experience: Master of Public Health

Suicide is a leading cause of death in adolescents and young adults, with a disproportionate burden of those deaths in rural areas such as Kansas. High rates of depressive symptoms, suicidal thoughts, and suicidal attempts, combined with a shortage of mental health providers, emphasize the need for community-based intervention.

This capstone is designed to develop a plan for Hope Kits, a proposed suicide prevention program, among youth in grades 7-12 in Sheridan County, Kansas to improve coping skills, promote help-seeking behavior, and reduce suicide risks.

A logic model guides the program development, which aligns with available literature and Social Cognitive …

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

Duncan NRI Faculty and Staff Publications

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

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

Duncan NRI Faculty and Staff Publications

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

Co-Creation Of Global Public Health Interventions Within The Context Of Limited Resources: A Conceptual Qualitative Framework For Modest Co-Creation, Kahabi Isangula, Constance Constance Shumba

School of Nursing & Midwifery, East Africa

Co-creation is increasingly promoted in global public health as a participatory methodology that centres lived experiences, the preferences, and structural realities of those most affected by health interventions. Within human-centred design (HCD), co-creation is typically operationalised through intensive cycles of qualitative inquiry, in-person workshops, facilitation, and iterative prototyping. While these approaches are methodologically robust, they are often resource-intensive and difficult to implement in low- and middle-income countries (LMICs) and other low resource settings, precisely where context-sensitive and equitable intervention design is most needed. Despite this tension, existing literature offers limited guidance on how co-creation can be meaningfully adapted to such …

Maternal, Perinatal, Neonatal, And Postpartum Outcomes Following Severe Acute Respiratory Syndrome - Coronavirus-2 Infection In Pregnancy: A World Health Organization Multi-Country Prospective Cohort Study, Edna Kara, Sami Gottlieb, Nathalie Broutet, Anna Thorson, Marie Delnord, Ibukun-Oluwa Abejirinde, Ronaldo Silva, Marleen Temmerman, Rodney Adam, Ingrid Gichere

Pathology, East Africa

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised global concerns regarding its impact on pregnant women and their infants, particularly across evolving variants. This study aimed to determine if infection during pregnancy increased the risk of adverse maternal, perinatal, neonatal, or postpartum outcomes during pre-Omicron and Omicron periods.

Methods We conducted a prospective cohort study in 10 primarily low- and middle-income countries, comprising public and private maternity hospitals in rural and urban areas. Maternal age and comorbidity adjusted mixed-effects models with country-specific random intercepts were used to estimate relative risks (RRs) comparing participants with and without infection …

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

Faculty, Staff and Students Publications

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

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

Current Practices Of Index Hospitalization Anticoagulant Use In Pediatric Patients With Acute Myeloid Leukemia., Abbey Elsbernd, Natalie Grills, James W. Antoon, Kathyrn Kyler, Lucas E. Orth, Timothy J. Savage, Matt Hall, Jennifer Goldman, Shannon L. Carpenter

Manuscripts, Articles, Book Chapters and Other Papers

Management and prevention of thromboembolism (TE) in pediatric acute myeloid leukemia (AML) are challenging because of prolonged periods of thrombocytopenia and associated bleeding. There are no guidelines for prophylactic or therapeutic anticoagulation for children with AML. This study aimed to understand the use of anticoagulation and its association with bleeding events (BEs) during index hospitalization in children with AML, both with and without thromboses. A retrospective cohort study was performed using the Pediatric Health Information System administrative database of index hospitalizations for patients aged 1 to 21 years from 2016 to 2024 with the diagnosis of AML across 49 children's …

Are We Winning At Twinning? Persistent Cni Use In Identical Kidney Transplants., Nicholas S. Herrera, Shivani Wadnerkar, Diane M. Cibrik

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS).

METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year …

Demographic And Clinical Characteristics Of Participants In The Neuropsychiatric Genetics Of African Populations-Psychosis (Neurogap-Psychosis) Study: A Descriptive Analysis, Rocky Stroud, Kimberly Hook, Melkam Alemayehu, Lukoye Atwoli, Mark Baker, Lori Chibnik, Bizu Gelaye, Stella Gichuru, Symon Kariuki, Rehema Mwema

Internal Medicine, East Africa

Background Approximately 1.3 million individuals in sub-Saharan Africa, as well as millions of others worldwide, live with psychotic disorders. However, there is limited mental health research based on these populations and even less of a focus on neuropsychiatric genetics research within these settings.

Methods To address this gap, the Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis), a case-control study, collected data identifying genetic and environmental risk factors associated with psychotic disorders in Ethiopia, Kenya, South Africa, and Uganda. This paper describes baseline demographic and clinical characteristics of the 42,953 participants recruited between 2018–2023 and compares these characteristics by country and case …

Exploring The Paradoxical Association Between Chest Ct Pulmonary Involvement And Olfactory Dysfunction In Covid-19 Patients: A Prospective Cross-Sectional Study, Abdolkarim Ghadimi-Moghadam, Saed Askari, Mohammad Amin Ghatee, Alireza Mortazavi, Saeed Javdansirat, Ali Ghadimi Moghadam, Hassan Vafapour, Zaker Salehi, Seyed Mohammad Javad Mortazavi, Lembit Sihver

Informatics and Engineering Systems Faculty Publications

Background and Aims: Olfactory dysfunction (OD) is common in COVID-19, yet its relationship with pulmonary involvement remains inconsistent. We evaluated the association between CT-based lung involvement and OD in laboratory-confirmed COVID-19.

Methods: In a prospective cross-sectional study (Yasuj University of Medical Sciences hospitals; December 26, 2021–May 22, 2022), OD was assessed using the CCCRC protocol and pulmonary involvement was categorized using a CT lung involvement score. Associations were examined using chi-square testing (categorical) and ANOVA where appropriate (α = 0.05).

Results: Among 120 patients (60 male/60 female; mean age 43.17 ± 14.76 years), 71 (59.2%) had hyposmia, and none had …

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

Duncan NRI Faculty and Staff Publications

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

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

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

Arts & Sciences Graduate Student Theses and Dissertations

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

The Effects Of Education And Training On Clinical Staff’S Knowledge, Perception, And Clinical Practice Of The Medication Reconciliation Process, Stephanie A. Williams

Doctor of Nursing Practice Projects

Medication-related harm affects approximately one in 30 patients in healthcare settings. Accurate medication reconciliation (MedRec) is essential for identifying medication discrepancies, preventing medication errors, and reducing adverse drug events. Clinical staff play a critical role in ensuring the accuracy of medication lists in primary care settings.

This evidence-based quality improvement project evaluated the effect of a structured MedRec training intervention on MedRec knowledge, perceptions, and practices among clinical staff in a primary care clinic in Southeast Texas. The project used a single-group, quantitative, quasi-experimental design. A convenience sample of 32 clinical staff members completed knowledge and perception assessments before and …

How Recent Medicaid Defunding Has Impacted San Bernardino County Residents Access To Health Care Services, Samantha I. Rios

Electronic Theses, Projects, and Dissertations

Background: Medicaid is a critical source of health insurance for low-income populations in the United States, providing access to essential preventative, primary, and reproductive health care services (Donohue et al., 2022). The Medicaid defunding of 2025 and policy changes that follow have raised concerns regarding increased barriers to care, particularly among low-income and vulnerable populations who rely on safety-net providers such as Planned Parenthood (Planned Parenthood, 2025). The purpose of this study was to examine how the 2025 Medicaid defunding has impacted access to general and reproductive health care services among residents of San Bernardino County, California.

Conclusion: The research …

A Culturally Responsive Sexual Health Education Framework For Community Clinics In The Inland Empire, Lilianna Mora Ledezma

Electronic Theses, Projects, and Dissertations

Sexually transmitted infections (STIs) continue to disproportionately affect underserved communities, where barriers such as limited healthcare access, stigma, healthcare anxiety, medical mistrust, and language differences may discourage individuals from seeking routine screening and timely treatment. This project examined current public health literature, surveillance data, and federal guidance to identify evidence-based strategies that community clinics can implement to improve patient engagement in sexual health services. The findings demonstrated that effective STI prevention extends beyond testing alone and is strengthened through culturally responsive care, stigma reduction, patient-centered communication, standardized clinic workflows, and effective patient navigation. As a result, this project developed a …

The Effect Of Telehealth Expansion On The Health Equity Of Underserved Populations, Mansi B. Satani

Electronic Theses, Projects, and Dissertations

The rapid expansion of telehealth, during and after the COVID-19 pandemic, has changed healthcare delivery in the United States. The use of telehealth can potentially decrease disparities related to isolation, shortage of providers and barriers to transportation, however, its impact on health equity in underserved populations is unknown. This paper explores how telehealth expansion impacts rural populations' access to healthcare, health outcomes, and equity. It also examines its impact on populations with low income, racial, ethnic minorities, and Medicaid recipients who frequently encounter obstacles to healthcare and digital access (Nouri et al., 2020; Shah et al., 2024). A mixed-method design …

How Establishing "Duration Of Treatment" Guidelines Shortens Workers' Compensation Cases, Annette Marie Smith M.D.

Electronic Theses, Projects, and Dissertations

Jobs provide financial security for individual workers and their families in the community until a worker gets hurt on the job, and then things are up in the air until their workers’ compensation claim is approved. It is a well-known fact within the workers compensation literature that one third of all workers’ compensation (WC) claims are “low back sprains and strains” which are the leading cause of global disability (Ummey, 2023). This project proposed to explore the relationship of x-ray and MRI result interpretations by the physician and standardize the duration of treatment with a physical therapist and new concept …

Decision-Making Criteria In Polygenic Embryo Screening: A Survey Of Reproductive Medicine Physicians, Rémy A Furrer, Aayushi Gandhi, Dorit Barlevy, Shai Carmi, Todd Lencz, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) examines embryos for their genetic likelihood of developing complex conditions and traits. The commercialization of PES places reproductive endocrinologists and infertility specialists (REIs) as the primary decision-makers in its use, despite professional guidelines cautioning that PES is not ready for clinical use.

Methods: This survey examines how 152 US REIs perceive and approach potential clinical decision-making scenarios regarding the use of PES.

Results: REIs were more likely to offer PES for medical conditions (up to 62% for cancer) than for traits (eg, 0% for skin color, 10% for body mass index). When evaluating 11 potential …

Navigating The Dark Side: Emotional Labor's Impact On Hr Professionals' Wellness, Esmeralda Amelia Rendón

Electronic Theses and Dissertations

This qualitative descriptive study was designed to document and describe how female-identifying human resource (HR) generalist practitioners serving as sole or primary employee relations practitioners in small- to medium-sized organizations across the United States experience and manage emotional labor in their roles, cope with its demands, and how these experiences impact their wellness and perceptions of organizational support. Despite the centrality of emotional labor (EL) in human resource professionals’ (HRPs) roles, little was known about how HRPs in these underresourced environments cope with these demands. Data were collected through semistructured virtual interviews with eight participants and analyzed using Braun and …

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.

Research design and methods: We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Results: There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, …

Obsessive-Compulsive Training Experiences In United States (Us) Medical School Education Programs, Carlos Valenzuela-Flores, Leanne Maduka, Dale Shepherd, Megan C Alam, Juliana E Avery, Hannah C Moore, Gian Depamphilis, Megan M Dailey, Caitlin M Pinciotti, Andrew D Wiese, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Objective: To evaluate the content and structure of OCD-specific training within United States osteopathic (D.O.) and allopathic (M.D.) medical schools. Although many physicians encounter patients with obsessive-compulsive disorder (OCD) in clinical practice, limited familiarity with the full range of OCD presentations, including typical and atypical forms, may contribute to misdiagnosis and delays in accurate diagnosis and treatment.

Methods: Respondents from 35 of the 154 (22.73%) medical schools within the United States (28 (80%) allopathic, 7 (20%) osteopathic schools) completed a survey assessing demographics, school information, and OCD-focused training within medical school curriculums. Descriptives were gathered to characterize the level of …

Colocalization Of Eqtls With Type 2 Diabetes And Glycemic Traits Using Whole-Genome Sequences In Diverse Populations From The Nhlbi Trans-Omics In Precision Medicine (Topmed) Program, Ningyuan Wang, Daniel A Dicorpo, Yixin Zhang, Erica Kleinbrink, Donna K Arnett, John Barnard, John Blangero, Donald W Bowden, April P Carson, Yii-Der Ida Chen, Mina K Chung, Joanne E Curran, Dawood Darbar, Ravindranath Duggirala, Patrick T Ellinor, Diane Fatkin, Myriam Fornage, Nancy Heard-Costa, Jiang He, Lifang Hou, Sharon L R Kardia, Charles Kooperberg, Ruth J F Loos, David D Mcmanus, Braxton D Mitchell, Ryan L Minster, Kari E North, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Dan Roden, Jerome I Rotter, Moore B Shoemaker, Jonathan D Smith, David R Van Wagoner, Francois Aguet, Kristin Ardlie, Joshua C Bis, Jennifer A Brody, Brian E Cade, Clary B Clish, Paul S De Vries, James S Floyd, Barry I Freedman, Stacey Gabriel, Robert E Gerzsten, Mark O Goodarzi, Charles Gu, Xiuqing Guo, Namrata Gupta, Susan R Heckbert, Sarah Hsu, Yi-Jen Hung, Rita R Kalyani, Tanika N Kelly, Gregory L Kinney, Changwei Li, Simin Liu, Yongmei Liu, Donald M Lloyd-Jones, Joann E Manson, Rasika A Mathias, Josep M Mercader, Alanna C Morrison, Take Naseri, Suna Onengut, Nicholette D Palmer, Patricia A Peyser, Qibin Qi, Sridharan Raghavan, Alex P Reiner, Mary R Rooney, Magdalena Sevilla-Gonzalez, Chloe Sarnowski, Joshua D Smith, Jennifer A Smith, Nicole L Spartano, Usman Tahir, Kent D Taylor, Deirdre K Tobias, Russel P Tracy, Satupa'itea Viali, Heming Wang, Alexis C Wood, Lisa R Yanek, Wei Zhao, Yinan Zheng, Josée Dupuis, Ching-Ti Liu, Robert Sladek, Jennifer Wessel, James B Meigs, Alisa K Manning, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium

Faculty, Staff and Students Publications

Large-scale multiancestry genome-wide association studies have identified hundreds of loci associated with type 2 diabetes (T2D) and glycemic traits, yet imputed genotyping arrays limit the detection of low-frequency and rare variants. Whole-genome sequencing (WGS) offers a more complete view of genetic variation, especially across diverse populations. We analyzed high-coverage (38×) WGS data from 21,913 T2D case subjects, 61,036 control subjects, and up to 50,011 individuals with no diabetes with fasting glucose, fasting insulin, and HbA1c from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program. We performed single-variant association testing, conditional analysis, fine-mapping, and Bayesian colocalization to …

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

Faculty, Staff and Students Publications

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

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

The Kdm-Family Inhibitor Jib-04 Sensitizes Aml Cells To Venetoclax By Inducing A Ferroptosis-Like Phenotype, Katharina Wohlan, Dandan Fan, Anna G Guzman, Alexis Quezada, Hyunji Park, Elmira Khabusheva, Farzane Sivandzade, Matthew Wither, Amber Alcorn, Tamara Thevarajah, Steven M Kornblau, Courtney D Dinardo, Jianzhong Su, Margaret A Goodell, Rachel E Rau

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with various molecular and cytogenetic subtypes. Treatment options for older adult patients are limited due to high toxicity of conventional chemotherapy. The B-cell leukemia/lymphoma 2 inhibitor venetoclax is effective in combination with hypomethylating agents or low-dose cytarabine, but ∼30% of patients do not respond to the initial combination treatment. Thus, alternative combinations are needed to sensitize AML cells to venetoclax and overcome resistance mechanisms. Here, we report that targeting histone lysine-specific demethylases induces a ferroptosis-like phenotype driven by oxidative stress in various AML subtypes. In both patient samples and cell lines, …

Multi-Level Disparities In Survival Among Patients Diagnosed With Oral Cavity Cancer In Texas Between 1995 And 2020, Guillermo A Tortolero, Erich M Sturgis, Jose-Miguel Yamal, Melissa F Peskin, Cici Bauer, Caitlin C Murphy

Faculty, Staff and Students Publications

Background: Multi-level factors, including demographic and neighborhood social conditions, related to disparities in oral cavity cancer (OCC) are not fully understood. We examined the association between these factors and survival outcomes among patients diagnosed with OCC.

Methods: We identified 14,416 patients diagnosed with OCC from 1995 to 2020 using population-based data from the Texas Cancer Registry. Neighborhood-level social vulnerability was measured using the 2010 US Centers for Disease Control and Prevention's Neighborhood Social Vulnerability Index (CDC-SVI). We examined race and ethnicity, CDC-SVI (as sample-based quintiles), and their joint effects with survival outcomes.

Results: Five-year survival probability was 38.6% (95% CI: …

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

Faculty, Staff and Students Publications

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

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