Digital Commons Network^™

Daily Rhythms In Psychosocial Stress, Sleep, And Mood: A Multimethod Approach To Transdiagnostic Psychopathology Risk And Intervention, Gabriel Gilmore

Theses and Dissertations--Psychology

Rhythms are central to nearly every core physiological and psychological process and have profound influences on overall health and well-being, particularly in the context of mood disorders. This dissertation emphasizes a rhythm-centered framework for understanding transdiagnostic psychopathology, proposing that the temporal organization of psychosocial stress, sleep, and mood provides crucial information for the development and treatment of mood disorder symptomology. Current literature relies primarily on mean symptom levels, overlooking day-to-day patterns in psychosocial experiences. To address this key methodological gap, three studies are examined. Study 1 develops and validates the Psychosocial Stress Regularity Measure (PSRM), a brief single-item measure of …

The Relationship Between Estradiol And Progesterone Concentration Levels, Alcohol Consumption, And Inhibitory Control, Layne Elizabeth Robinson B.S.

Theses and Dissertations--Psychology

Alcohol use is increasing among women, with estimates for binge drinking having risen to levels similar to those seen in men. Despite this trend, sex differences regarding mechanisms of alcohol consumption have seldom been investigated. Our group and others have found evidence to suggest that ovarian sex hormones are associated with alcohol consumption and mechanisms that might be related to alcohol consumption, such as executive function deficits. The current study sought to extend this prior research in a larger sample with higher drinking rates and more rigorous methods, and to explore inhibitory control associations with drinking. Across the two samples …

Effects Of Transcranial Direct Current Stimulation On Urge During Cue-Exposure To Body-Focused Repetitive Behaviors, Hannah Rebecca Wild

Theses and Dissertations--Psychology

Body-focused repetitive behaviors (BFRBs) are unnecessary, repetitive grooming behaviors linked to abnormalities in sensory and reward processing, as well as top-down inhibition. The left dorsolateral prefrontal cortex (dlPFC) is implicated in these processes and plays a key role in cravings among individuals facing addiction. Transcranial direct current stimulation (tDCS) targeting the left dlPFC shows promise in reducing craving for addictive substances. Despite phenomenological similarities between BFRBs and addictive disorders, no controlled studies have examined tDCS’s effect on BFRBs. This study used a randomized, double-blind design to examine whether a single session of anodal multifocal tDCS targeting the left dlPFC reduced …

Correlates Of Recovery Capital Among Women In Jails: Leveraging A Dimensional Recovery Framework, Amanda Fallin-Bennett, Martha Tillson, Jaxin Annett, Hartley Feld, Michele Staton

Nursing Faculty Publications

Background: Recovery capital encompasses internal and external factors that support recovery from substance use disorder, such as employment, social support, and physical and mental health. There is a need for more research on recovery capital among women who are incarcerated, who often face complex barriers to recovery, such as poverty, unemployment, and histories of trauma.

Methods: Women (N ¼ 900) were recruited from Kentucky jails as part of the broader NIDA-funded Kentucky Justice Community Opioid Innovation Network (JCOIN) cooperative project. Measures from baseline interviews (during incarceration) were selected in alignment with the Substance Abuse Mental Health Service Administration (SAMHSA)’s four …

Unexpected Longevity In Myasthenia Gravis, Bhupendra O. Khatri, Scott Schutten, Sergey Tarima

Biostatistics Faculty Publications

Background: This study compares age at death in patients with myasthenia gravis (MG) and multiple sclerosis (MS) with the general U.S. population and examines age at death patterns during a period preceding modern high-efficacy therapies. Objective: To compare age at death among individuals with MG and MS with the general population and assess differences in age at death between MG and MS. Design: Retrospective population-based study using death certificate data from four U.S. states (Florida, Wisconsin, Texas, and New York) for 2000, 2005, 2010, and 2015. Methods: Individuals with MG or MS listed on death certificates were identified. Age at …

Integration Of Community-Engaged Research Technology And Methods To Guide Tobacco Regulatory Science In Rural Communities, Melissa H. Abadi, Stephen R. Shamblen, Mary Kay Rayens, Kirsten T. Thompson, Amy Wildman, Kathy Rademacher, William Wieczorek, Raphael Nishimura, Shyanika W. Rose, Mikhail N. Koffarnus, Seth Himelhoch, Ellen J. Hahn

Biostatistics Faculty Publications

Objective – This study aims to build a rural Appalachian cohort to examine how US Food and Drug Administration (FDA) Center for Tobacco Products (CTP) regulatory policies influence tobacco and nicotine product use across levels of rurality. Methods – The AppalTRUST (Appalachian Tobacco Regulatory Science Team) Cohort integrates four inter-connected Community-engaged Research + Technology (CEnRT) elements to support recruitment and retention: (1) building trust and cultural relevance; (2) addressing barriers to participation in research; (3) focusing on ethics and confidentiality; and (4) fostering ongoing and consistent collaboration between the scientific and field teams. The study uses a dual sampling design …

Leveraging Community Health Worker’S Deep Community Knowledge To Address Food And Nutrition Security In Appalachia, Alexis Kimbro Scott, Melissa D. Olfert, Dawn Brewer, Makenzie Barr, Julie Plasencia

Journal of Appalachian Health

Introduction: Community health workers (CHWs) are trusted professionals in communities because of the deep understanding and cultural insights learned from their lived experiences. In Appalachia, CHWs are embedded in the community, giving them a unique understanding of how social determinants, like food and nutrition security, impact health outcomes.

Purpose: This study aimed to examine the professional characteristics and knowledge of CHWs while identifying culturally sensitive practices around food insecurity.

Methods: This cross-sectional, mixed-methods study used an online survey and in-depth phone interviews with CHWs in the Appalachian Region to examine their professional characteristics and knowledge on food security in their …

Influence Of Family Health History And Parental Education On Body Mass Index, Blood Pressure, And Lipid Levels In 5th Grade Children: A Secondary Data Analysis Of The Cardiac Project, Madha Rani Das, Lee A. Plyes, Eloise Elliott, Christa L. Lilly

Journal of Appalachian Health

Introduction: Childhood obesity and related cardiovascular risks reflect the interplay of genetic predispositions and socioeconomic adversity. Appalachia’s poverty, limited health care, and educational gaps worsen family health risks, driving early cardio-metabolic problems in children, highlighting the need for effective interventions.

Purpose: The purpose of this study is to examine the association of family health history and parental education with BMI, BP, and lipid profiles among 5^th grade children in West Virginia (WV).

Methods: The study used WV CARDIAC data from 2006–2009. Outcomes were BMI, SBP/DBP, and fasting lipids (HDL, LDL, TG). Predictors were parental education and family health history …

Migratory Songbirds As Potential Ectozoochorous Protist Dispersal Vectors, Silas E. Fischer, Joy J. Jackson, Elise C. Hoffman, Henry M. Streby, Trisha L. Spanbauer

Earth and Environmental Sciences Faculty Publications

Protist biogeography, speciation, and systematics continue to generate debate and inquiry because protist distributions and dispersal remain poorly resolved. Identifying potential vectors and basibionts for epibiont protists would contribute to our limited understanding of their ecology. Migratory animals seasonally link disparate landscapes, incidentally transporting other organisms in the process. Waterbirds are known microbe dispersers, but evidence for other avian groups is limited-such as taxa that often migrate longer distances. We asked whether terrestrial songbirds (Passeriformes) host diatoms (Bacillariophyta) by sampling tail plumage of four thrush species (Hermit Thrush Catharus guttatus, Swainson's Thrush C. ustulatus, Wood Thrush Hylocichla mustelina, American Robin …

Trends In Cardiovascular Disease Prevalence Among Adults With Type 1 Diabetes In The Usa, Orighomisan Freda Agboghoroma, Kory R. Heier, Omer Atac, Meredith S. Duncan, Anna Kucharska-Newton, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

Introduction Cardiovascular disease (CVD) is a common complication and major cause of mortality in people with type 1 diabetes (T1D). This study quantifies the prevalence of CVD among commercially insured adults with T1D in the USA from 2017 to 2021, overall and among age-defined and sex-defined subgroups. Research design and methods We used Merative MarketScan nationwide commercial insurance claims database (2017–2021) to identify adults ≥20 years with T1D (International Classification of Diseases, 10th Revision (ICD-10) codes). CVD ascertainment was based on ICD-10 codes for myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, peripheral artery disease, and stroke. Comorbidities included …

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer’S Disease, Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan Ping Lee, Jacob Haut, Kara L. Hamilton-Nelson, Nicholas R. Wheeler, Yi Zhao, John J. Farrell, Michelle A. Grunin, Yuk Yee Leung, Pavel P. Kuksa, Donghe Li, Eder Lucio Da Fonseca, Jesse B. Mez, Ellen L. Palmer, Jagan Pillai, Richard M. Sherva, Yeunjoo E. Song, Xiaoling Zhang, Takeshi Ikeuchi, Taha Iqbal, Omkar Pathak

Epidemiology and Environmental Health Faculty Publications

Background : Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer’s Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer’s disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. Results: We identify 13 loci with cross-population associations including known loci at/near …

Probing Tau Citrullination In Alzheimer’S Disease Brains And Mouse Models Of Tauopathy, Huimin Liang, Jerry B. Hunt, Chao Ma, Andrii Kovalenko, John Calahatian, Cecelie Pedersen, Haiying Liu, Junyan Li, Malina Serrano, Danielle Blazier, Mallory Watler, Patricia Rocha-Rangel, Christopher Saunders, Laura J. Blair, Leonid Breydo, Kevin Nash, Zainuddin Quadri, Brian Kraemer, Peter Nelson, Christopher Norris, Erin L. Abner, Vladimir N. Uversky, Dale Chaput, Maj Linda B. Selenica, Daniel C. Lee

Epidemiology and Environmental Health Faculty Publications

Alzheimer’s disease (AD) includes a defining hallmark that correlates most closely to cognitive decline, namely misfolded tau protein. However, the “upstream” etiology and downstream clinical manifestations of tauopathies are quite diverse. Tau deposition elicits different pathological phenotypes and outcomes depending on the tau strain, proteoforms, and regional susceptibility. Posttranslational modifications (PTM) can alter tau structure, function, networks, and its pathological sequelae. We uncovered tau citrullination on multiple epitopes caused by peptidyl arginine deiminase (PAD) enzymes. PAD-induced citrullination irreversibly converts arginine residues to citrulline, producing a net loss of positive charge, elimination of pi–pi interactions, and increased hydrophobicity. We observed increased …

Multiple Bursts Of Speciation In Madagascar’S Endangered Lemurs, Kathryn M. Everson, Luca Pozzi, Meredith A. Barrett, Mary E. Blair, Mariah E. Donohue, Peter M. Kappeler, Andrew C. Kitchener, Alan R. Lemmon, Emily Moriarty Lemmon, Carlos J. Pavón-Vázquez, Ute Radespiel, Blanchard Randrianambinina, Rodin M. Rasoloarison, Solofonirina Rasoloharijaona, Christian Roos, Jordi Salmona, Anne D. Yoder, Rosana Zenil-Ferguson, Dietmar Zinner, David W. Weisrock

Biology Faculty Publications

Lemurs are often cited as an example of adaptive radiation, as more than 100 extant species have evolved and filled ecological niches on Madagascar. However, recent work suggests that lemurs lack a hallmark of other adaptive radiations: explosive speciation rates that decline over time. Thus, characterizing the tempo and mode of evolution in lemurs can reveal alternative ways that hyperdiverse clades arise over time, which might differ from traditional models. We explore lemur evolution using a phylogenomic dataset with broad taxonomic sampling that includes the lorisiforms of Asia and continental Africa. Our analyses reveal multiple bursts of diversification (without subsequent …

Acute Effects Of Lactate Infusion On Metabolism, Ad Biomarkers, And Cognition, Riley E. Kemna, Paul J. Kueck, Anneka Blankenship, Casey S. John, Chelsea N. Johnson, Zachary D. Green, Hana Mayfield, Lauren Yoksh, Lance Johnson, John P. Thyfault, Jonathan D. Mahnken, Benjamin F. Miller, Jill K. Morris

Physiology Faculty Publications

BACKGROUND: Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. METHODS: The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). RESULTS: …

Inhibition Of Astrocyte Signaling Leads To Sex-Specific Changes In Microglia Phenotypes In A Diet-Based Model Of Cerebral Small Vessel Disease, Jenna L. Gollihue, Khine Zin Aung, Colin B. Rogers, Leopoldine B. Galopin, Nicholas A. Wright, Pradoldej Sompol, Erica M. Weekman, Yuriko Katsumata, Josh M. Morganti, Christopher M. Norris

Physiology Faculty Publications

Hyperhomocysteinemia (HHcy)-inducing diets recapitulate cerebral small vessel disease phenotypes in mice including cerebrovascular pathology/dysfunction, neuroinflammation, synaptic deficits, and cognitive decline. We recently showed that astrocyte signaling through calcineurin(CN)/nuclear factor of activated T cells (NFATs) plays a causative role in these phenotypes. Here, we assessed the impact of astrocytic signaling on microglia, which set the inflammatory tone in brain. Seven-to-eight-week-old male and female C57BL/6 J mice received intrahippocampal injections of adeno-associated virus (AAV) expressing EGFP (AAV2/5-Gfa2-EGFP) or AAV expressing the NFAT inhibitor VIVIT (i.e., AAV2/5-Gfa2-VIVIT-EGFP). Mice were then fed with control chow (CT) or B-vitamin-deficient chow for 12 weeks to induce …

Mirabegron Treatment Reduces Myofibroblasts And Cxcr2 Expression In Adipose Tissue In Obesity, Brian S. Finlin, Hasiyet Memetimin, Philip M. Westgate, Jin Chen, Esther E. Dupont-Versteegden, Philip A. Kern

Physiology Faculty Publications

Background: Treatment with the β3-adrenergic receptor (AR) agonist mirabegron improves insulin sensitivity β, cell function, and glucose tolerance in individuals with obesity, without weight loss or a change in brown adipose tissue (BAT) (Finlin et al, J Clin Invest. 2020 May 1;130(5):2319-2331). Furthermore, mirabegron treatment increased protein expression of beige adipose markers and the number of anti-inflammatory macrophages, and changed the expression of genes involved in fibrosis and tissue remodeling in subcutaneous white adipose tissue (SC WAT). Methods: We utilized RNA seq and enrichment analysis to identify biological pathways changed by mirabegron treatment in SC WAT thigh biopsies. We verified …

Emergence Of Inflammatory Fibroblasts With Aging In Hermansky-Pudlak Syndrome Associated Pulmonary Fibrosis, Brandon J.H. Banaschewski, Sylvia N. Michki, Sneha Sitaraman, Ruby Pan, Joanna Y. Wang, Dominique Stewart, Mary Kate Goldy, Susan M. Lin, Edward Cantu, Jeremy B. Katzen, Maria C. Basil, Amir M. Emtiazjoo, Jamie L. Todd, Jason J. Gokey, Jonathan A. Kropski, David B. Frank, Jarod A. Zepp, Lisa R. Young

Surgery Faculty Publications

The longitudinal cellular interactions that drive pulmonary fibrosis are not well understood. To investigate the disease underpinnings associated with fibrosis onset and progression, we generated a scRNA-seq atlas of lungs from young and aged mouse models of multiple subtypes of Hermansky-Pudlak syndrome (HPS), a collection of rare autosomal recessive diseases associated with albinism, platelet dysfunction, and pulmonary fibrosis. We have identified an age-dependent increase in SAA3⁺ inflammatory lung fibroblasts in HPS mice, including in double-mutant HPS1-2 mice which develop spontaneous fibrosis. HPS1 fibroblasts show increased expression of IL-1R1, whereas alveolar type II epithelial cells from HPS2 mice induce the …

Genomic, Transcriptomic, And Immunogenomic Landscape Of Over 1300 Sarcomas Of Diverse Histology Subtypes, Alex Soupir, Oscar E. Ospina, Oliver Hampton, Michelle Churchman, Michael Radmacher, Dale Hedges, David Mckean, Phaedra Agius, Saman Zeeshan, Nathan D. Seligson, Raphael Pollock, David Liebner, James L. Chen, Gabriel Tinoco, Bodour Salhia, Martin Mccarter, Breelyn A. Wilky, Benjamin J. Miller, Michael J. Cavnar, John S. Groundland, Bryan P. Schneider, Gregory Riedlinger, Stephen B. Edge, Christopher A. Moskaluk, Kenneth Cardona, Abdul Rafeh Naqash, Ricardo J. Gonzalez, John E. Mullinax

Surgery Faculty Publications

Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. To better define the molecular landscape of this group of diseases, we perform matched whole exome sequencing and RNA sequencing on a cohort of 1340 sarcoma tumor specimens. We identify recurrent somatic mutations and observe an increased mutational burden in metastatic vs. primary samples (p < 0.001). We observe frequent copy number alterations including whole genome doubling, with this feature being more common in metastatic tumors (p = 0.026). Estimation of immune cell abundances followed by hierarchical clustering identifies five immune subtypes ranging from low to high and we observe inferior overall survival in immune deplete clusters compared to immune enriched (p < 0.01). Interestingly, GIST predominantly form a distinct “immune intermediate” cluster that is marked by a specific enrichment for NK cells (FDR < 0.01).

Mir-181a-5p Mediates The Effects Of Bmp4 On Intestinal Cell Proliferation And Differentiation, Chang Li, Yuning Zhou, Zhijie Yin, Yinping Jiang, Jinpeng Liu, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Surgery Faculty Publications

The intestinal mucosa undergoes a dynamic process of continual proliferation, differentiation, and apoptosis. Delineating the mechanisms involved in intestinal epithelial cell (IEC) differentiation is crucial to our understanding of not only normal gut adaptation but also aberrant intestinal growth. Bone morphogenetic protein (BMP) signaling is a pivotal regulator of intestinal proliferation and differentiation. However, the molecular underpinnings of the BMP pathway in this context are not entirely known. Here, we show a key role for the BMP4/microRNA (miR)-181/glycolysis signaling pathway in the maintenance of intestinal epithelial cell proliferation and differentiation. Treatment with BMP4 increased the expression of enterocyte markers and …

Prevalence And Biological Impact Of Clinically Relevant Gene Fusions In Head And Neck Cancers, Emily L. Hoskins, Raven Vella, Julie W. Reeser, Michele R. Wing, Eric Samorodnitsky, Altan Turkoglu, Leah Stein, Elizabeth Breuning, Zachary A. Risch, Wilnelly M. Hernandez-Sanchez, Lianbo Yu, Michelle Churchman, Nancy Single, Jad Chahoud, Antonio Jimeno, Michael J. Cavnar, Matthew Reilley, Courtney Scaife, Kenneth G. Nepple, Minh Phan, Bryan Schneider, Stephen Edge, Bodour Salhia, Aliza Leiser, Trisha M. Wise-Draper, Michael K. Wendt, Sameek Roychowdhury

Surgery Faculty Publications

Head and neck cancer (HNC) is the seventh most common cancer worldwide. Currently-approved systemic therapies include chemotherapy, anti-EGFR antibodies, and PD-1 immunotherapy, with few genomic-based targeted therapies. Gene fusions involving cancer-driving kinase genes such as FGFR, NTRK, and ALK are clinically targetable in other solid tumors; however, there is limited knowledge about their prevalence in HNC. Here, we describe the genomic landscape and the biological impact of oncogenic fusions in a combined dataset of over 13,000 HNC tumors (excluding salivary gland tumors). We identified 66 cases (2.8%) harboring oncogenic fusions, including previously-reported FGFR3 fusions (n = 19) and gain-of-function EGFR …

Hiring Expectations For New And Future Workers In Animal Genetics Careers, Meghan C. Wulster-Radcliffe, James N. Macleod, Robert J. Coleman, John S. Radcliffe, Rebekah B. Epps, Carol D. Hanley, Cheyenne S. Summers, Steven A. Zinn, Sarah A. Reed

Animal and Food Sciences Faculty Publications

To better align educational outcomes with workforce demands in animal and equine genetics, this study surveyed 65 industry professionals on entry-level competencies, hiring trends, and graduate preparedness of undergraduate students. The survey assessed employer ratings on the importance and perceived proficiency of seven core competencies: critical thinking, communication, teamwork, leadership, professionalism, career/self-development, and equity/inclusion, as well as technical knowledge and broader skills relevant to animal breeding and genetics. Results revealed oral communication, teamwork, and work ethic were rated as the most critical transferable skills, though notable proficiency gaps persist, particularly in leadership and professionalism. Foundational technical knowledge in genetics, molecular …

Protein Structural Modeling Explains Rapid Oxidation In Poultry And Fish Myoglobins Compared To Livestock Myoglobins, Greeshma Sreejesh, Surendranath P. Suman, Gretchen G. Mafi, Morgan M. Pfeiffer, Ranjith Ramanathan

Animal and Food Sciences Faculty Publications

Background: This study aimed to investigate rapid oxidation in poultry and fish myoglobin compared to livestock myoglobin using protein structural differences and bioinformatics tools. Methods: Myoglobins from beef (Bos taurus), bison (Bos bison), sheep (Ovis aries), goat (Capra hircus), red deer (Cervus elaphus), pork (Sus scrofa), chicken (Gallus gallus), turkey (Meleagris gallopavo), yellowfin tuna (Thunnus albacares), and tilapia (Oreochromis niloticus) were analyzed to understand differences in structure and function that may influence oxidative behavior. Results: Fish and poultry had shorter or absent D-helix in their myoglobin structure than other species. Tilapia showed the largest heme cavity surface area, indicating significant …

Temporal Endocrine And Hematological Consequences Of Biological Extremes In Porcine Birth Weight, Alyssa A. Smith, Dayeon Jeon, Kaylyn Rudy, Sarah Innis, J. Scott Radcliffe, J. Alex Pasternak

Animal and Food Sciences Faculty Publications

To characterize the potential long-term impact of intrauterine growth restriction (IUGR), we assessed the endocrine and hematological consequences of IUGR at birth and in the early postnatal period. Piglets (n = 911) were collected pre-suckling, weighed, and blood sampled, with rectal temperatures assessed two hours later, and sampling repeated at 20 days of age (D20). A subset of piglets was classified as IUGR (n = 92) or large for gestational age (LGA; n = 92) based on birthweight. At birth, IUGR piglets had decreased T3 and T4 relative to LGA, which may be associated with concomitantly decreased rectal temperatures. T4 …

A Bioinformatic Survey Of Rna Isoform Diversity And Expression Across 9 Gtex Tissues Using Long-Read Sequencing Data, Madeline L. Page, Bernardo Aguzzoli Heberle, J. Anthony Brandon, Mark E. Wadsworth, Lacey A. Gordon, Kayla A. Nations, David W. Fardo, Mark T.W. Ebbert

Biostatistics Faculty Publications

Background: Even though alternative RNA splicing was discovered nearly 50 years ago (1977), we still understand very little about most isoforms arising from a single gene, including in which tissues they are expressed and if their functions differ. Human gene annotations suggest remarkable transcriptional complexity, with approximately 252,798 distinct RNA isoform annotations from 62,710 gene bodies (Ensembl v109; 2023), emphasizing the need to understand their biological effects. For example, 256 gene bodies have ≥ 50 annotated isoforms, and 30 have ≥ 100, where one protein-coding gene (MAPK10) even has 192 distinct RNA isoform annotations. Whether such isoform diversity results from …

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

Biostatistics Faculty Publications

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 (P_EA = 3.0 × 10^-8) fasting insulin PSs with total cranial volume, …

Quantifying Nuanced Differences In Hand Dexterity Between The Dominant And Nondominant Hands Of Healthy, Right-Handed, Young Adults, Brian J. Conway, Léon Taquet, Timothy F. Boerger, Kaitlin Goetschel, Kate B. Krucoff, Sergey Tarima, Brian D. Schmit, Max O. Krucoff

Biostatistics Faculty Publications

When individuals present with hand injuries, clinicians often use the contralateral hand as an internal control. However, subtle differences in baseline dexterous abilities between the dominant and nondominant hands are poorly understood. To address this gap, here we quantified such differences, measured as independence (individuation) and smoothness of finger movements. A cohort of 47 right-hand-dominant healthy adults (22 males and 25 females) moved each finger independently 10 times, while joint angle data were tracked with a dataglove (CyberGlove III, CyberGlove Systems, San Jose, CA). Each finger’s performance was compared with its counterpart on the opposite hand using Wilcoxon-signed rank tests. …

Genome Annotations Matter, Madeline L. Page, Mark E. Wadsworth, Bernardo Aguzzoli Heberle, David W. Fardo, Mark T.W. Ebbert

Biostatistics Faculty Publications

Background: An accurate genome annotation is essential in many contexts, including RNA sequencing studies. Annotations include known genes and isoforms, detailing their location (chromosome, start, and end) and coding sequence, among other important metadata. Results: We characterized changes in human Ensembl annotations from 2014 to 2023 and the important gains in our biological understanding in recent years. While generally gene and isoform annotations increased (2014: 58,812 genes ; 2023: 62,710), some years dropped (e.g., 2016). A similar pattern exists for the gene and isoform biotypes; both 2015 (19,825) and 2017 (19,828) have fewer genes annotated as protein-coding than 2014 (19,953) …

High-Throughput Screens Identify Genotype-Specific Therapeutics For Channelopathies, Christian L. Egly, Alex Shen, Tri Q. Do, Carlos Tellet Cabiya, Paxton A. Ritschel, Suah Woo, Matthew Ku, Brian P. Delisle, Brett M. Kroncke, Björn C. Knollmann

Physiology Faculty Publications

Genetic diseases such as ion channelopathies substantially burden human health. Existing treatments are limited and not genotype specific. Here, we report a 2-step high-throughput approach to rapidly identify drug candidates for repurposing as genotype-specific therapy. We first screened 1,680 medicines using a thallium-flux trafficking assay against Kv11.1 gene variants causing long QT syndrome (LQTS), an ion channelopathy associated with fatal cardiac arrhythmia. We identified evacetrapib as a suitable drug candidate that improves membrane trafficking and activates channels. We then used deep mutational scanning to prospectively identify all Kv11.1 missense variants in an LQTS hotspot region responsive to treatment with evacetrapib. …

Trajectories Of Recovery After Acute And Critical Illness (Tracer), Felipe González-Seguel, Louisa A. Summers, Lindsey E. Fresenko, Douglas E. Long, Logan N. Scott, Stacey A. Slone, Srushan Shankara Bhaktula, Yuan Wen, Benjamin F. Miller, Peter E. Morris, Amy L. Salyer, Anna G. Kalema, Ashley A. Montgomery-Yates, Esther E. Dupont-Versteegden, Kirby P. Mayer, Isabelle D. Bach, Davis A. Englund, Zachary R. Hettinger, Ahmed Ismaeel, Audrey M. Johnson, Philip A. Kern, Gerald V. Klim, Allison M. Owen, Jocelyn C. Porchia, Heba H. Qaissi

Physiology Faculty Publications

Introduction Patients who survive admission to intensive care unit (ICU) for critical illness are at high risk of developing muscle atrophy and weakness, commonly diagnosed as ICU-acquired weakness (ICUAW). The development of ICUAW is closely linked to long-term symptoms and impairments known as post-intensive care syndrome (PICS). Despite heightened recognition of impairments, there is limited research supporting effective interventions to improve muscle and physical outcomes after hospital discharge. Prior to developing and testing interventions for ICU survivors, it is imperative to understand the trajectory of muscle and physical function recovery following an ICU stay. The purpose of this study is …

Introducing Neuro Social Work: A Brief Reflection On Neuroscience And The Profession, Priscila Llamosa

Social Work Faculty Publications

Neuroscience offers language and evidence that can strengthen interdisciplinary communication, support advocacy in biomedically dominated settings, and validate relational practices long recognized in social work, including the impacts of early adversity, attachment, and healing through connection. At the same time, an epistemological tension underlies the profession’s unease with neuroscience when brain-based narratives are used to individualize structural harm or justify surveillance of marginalized families and communities. This teaching note introduces Neuro Social Work as a justice-oriented specialization that integrates contemporary neuroscience with social work’s person-in-environment commitments, relational practice traditions, and anti-oppressive ethics.The author argues that the key question is no …