Digital Commons Network^™

Protecting The Vulnerable: Elderly Population Change In Kentucky & Nursing Home Floodplain Proximity, David M. Stevens, Austin Matthew Mullen, Nicklaus P. Hammond

MPA/MPP/MPFM Capstone Projects

This study explores Kentucky’s changing vulnerability to flooding. Relying on America Community Survey (ACS) survey data estimates for 2019 and 2024, we illustrate how Kentucky’s elderly population has changed over this five-year period. Using nursing home data and floodplain spatial data, provided by the Centers for Medicare & Medicaid Services and FEMA respectively, we identify all 269 facilities and their proximity to floodplains across Kentucky. To narrow the scope of our study, we highlight counties that (a) have seen the largest percentage increase in elderly residents and (b) have a large total elderly population. Using a quartile ranking system, we …

Discovering Naturally Occurring Antifreeze Peptides From Microbiome By Integrating Protein Language Models And Molecular Dynamics Simulation, Ibrahim A. Imam, Trevor Morey, Yuexu Jiang, Duolin Wang, Dong Xu, Qing Shao

Chemical and Materials Engineering Faculty Publications

Antifreeze peptides inhibit ice crystal growth and recrystallization, and are promising components of cryoprotective formulations for cell, tissue, and food preservation, as well as anti-icing surface coatings. However, the discovery of new antifreeze peptides has been hindered by their sequence diversity and the limited scalability of experimental screening. In this study, we identify novel antifreeze peptide candidates from a microbiome-derived sequence library using ensemble machine learning and molecular dynamics (MD) simulations. We developed an ensemble classifier composed of 10 adapter-tuned protein-language models and a random forest meta-learner. After training on a curated dataset of 73 766 sequences, we applied this …

Functionalization Of Microfiltration Media Towards Catalytic Hydrogenation Of Selected Halo-Organics From Water, Subrajit Bosu, Samuel S. Thompson, Doo Young Kim, Noah D. Meeks, Dibakar Bhattacharyya

Chemical and Materials Engineering Faculty Publications

Contaminated water detoxification remains difficult due to the presence of persistent halo-organic contaminants, such as perfluorooctanoic acid (PFOA) and chlorophenols, which are chemically stable and resist conventional purification methods. Functionalized membrane-based separation and decontamination have garnered immense attention in recent years. Commercially available microfiltration membrane (PVDF) and polymeric non-woven fiber filters (glass and composite) are functionalized with poly(methacrylic acid) (PMAA) that shows outstanding pH-responsive performance and tunable water permeability under ambient conditions perfect for environmental applications. Polymer loading based on weight gain measurements on PMAA–microglass composite fibers (137%) and microglass fibers (116%) confirmed their extent of functionalization, which was significantly …

Bmal1 Mediates Sex-Specific Circadian Regulation Of Cardiac Ion Channels And Temporal Arrhythmia Vulnerability, Brian P. Delisle, Ezekiel Rozmus, Abhilash Prabhat, Spencer B. Procopio, Xiping Zhang, Emilia Entcheva, Karyn A. Esser, Elizabeth Schroder

Physiology Faculty Publications

No abstract provided.

C/Ebpα Is Essential For Gonadal But Not Inguinal White Adipose Tissue Formation In Mice, Krista Y. Hu, Yu-Lin Ma, Esme A. Dodge, Olivia A. B. Maguire, Caio V. Matias, Ryan K. Barney, Hector S. Himede, Juliana Gomez Pardo, Miriam Cepeda, Scott M. Gordon, Robert C. Bauer

Physiology Faculty Publications

Objective: The distribution of excess white adipose tissue (WAT) in obesity correlates with risk for comorbidities. Thus, understanding depot-specific WAT developmental mechanisms is translationally relevant. SNPs near the gene CEBPA associate with waist to hip ratio, and while C/EBPα is a recognized regulator of adipogenesis, there is no previously known role for C/EBPα in regulating adipose distribution.

Methods: We crossed Cebpa floxed mice to the AdipoQ-Cre transgenic mouse strain, generating mice with adipocyte-specific knockout of Cebpa (Cebpa_ASKO). Mice were phenotyped on a chow diet and after prolonged high-fat diet (HFD) feeding.

Results: Cebpa_ASKO mice almost entirely lack gonadal …

Dim Light At Night Worsens Cardiac Autonomic Dysregulation In Female Diabetic Mice, Abhilash Prabhat, Shrishti Naidu, Isabel G. Stumpf, Tanya S. Seward, Elizabeth A. Schroder, Brian P. Delisle

Physiology Faculty Publications

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. CAN is characterized by impaired cardiovascular autonomic control and is associated with increased mortality, especially among women with type 2 diabetes. Identifying environmental factors that exacerbate the CAN-associated phenotype may reveal modifiable strategies to reduce cardiovascular risk.

Nighttime light exposure is a novel cardiovascular risk factor. Among ∼90,000 individuals, greater nighttime light exposure correlated with increased atrial fibrillation and heart failure risk. Light at night disrupts sympathovagal balance and elevates nocturnal heart rate in humans. Dim light at night similarly disrupts autonomic regulation of heart rate in mice. We …

Pediatric Chop Chemotherapy Acutely Disrupts Satellite-Cell Dynamics And Blunts Muscle Mass In A Sex-Specific Manner, Jainil Daredia, Marc A. Magaña, Carla M.C. Nascimento, Jaden M. Wells, Nicholas T. Thomas, Yuan Wen, Savannah V. Rauschendorfer, Cory M. Dungan, Michael P. Wiggs

Physiology Faculty Publications

Pediatric cancer survival now exceeds 85% owing, in part, to advances and the use of combination chemotherapy treatments such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Despite its efficacy, CHOP may cause off-target effects during critical pediatric development periods such as impairments of skeletal muscle. We evaluated the acute effects of a CHOP administered to C57Bl/6J mice from postnatal day 28 to 48. CHOP slowed body-weight gain and led to a smaller gastrocnemius fiber cross-sectional area by ~25% in both sexes (n ¼ 11 or 12 males; n ¼ 8 or 9 females). RNA sequencing detected 214 differentially expressed genes …

Skeletal Muscle Methylome-Transcriptome Disruptions During The Onset And Progression Of Colorectal Cancer-Induced Cachexia, Ana Regina Cabrera, Ronald G. Jones, Eleanor R. Shrems, Francielly Morena, Yuan Wen, Tyrone A. Washington, Kevin A. Murach, Nicholas P. Greene

Physiology Faculty Publications

Cancer cachexia is a wasting condition, primarily affecting skeletal muscle, impairing patients’ quality of life, prognosis, and survival. The molecular triggers are incompletely defined, but given prior evidence for epigenetic plasticity in muscle, we speculate that dysregulated DNA methylation plays a role in muscle transcriptional alterations mediating cachexia severity. We aimed to describe and integrate the cachexia methylome and transcriptome. We used a time course approach in a mild cachexia model (colon-26, C26) coupled with a severe cachexia genetic model (Apc^Min/+) in both biological sexes to assess the methylome across degrees of cachexia pathology. The muscle methylome and …

Cytoprotective Role Of Octacosanol In Lipopolysaccharide-Induced Inflammation, Jingrong Tang, Zhi Hong Yang, Wenling Li, Huaitian Liu, Diego Lucero, Denis Sviridov, Olivia White, Julia Kun, Yoh Suke Mukouyama, Alan T. Remaley

Physiology Faculty Publications

Inflammation and endothelial dysfunction are key steps in the pathogenesis of atherosclerosis. Octacosanol (C₂₈H₅₈O, OCT), a very-long-chain saturated aliphatic alcohol (VLCA) with 28 carbons, is the main component of policosanol, a nutraceutical mixture of VLCAs (C20-C34) extracted from plants. Polycosanol in animal models is known to reduce atherosclerosis, but its mechanism of action remains unclear. This study investigates the pathways by which OCT alleviates LPS-induced inflammation in primary human aortic endothelial cells (HAECs). After overnight pretreatment with purified OCT, inflammation in HAECs was induced by lipopolysaccharide (LPS) at 100 ng/ml. The effects of OCT on the …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G. Clina, Brian C. Helsel, Sigan L. Hartley, David A. White, Victoria L. Fleming-Batayneh, Benjamin Handen, Bradley Christian, Elizabeth Head, Mark Mapstone, Christy L. Hom, Beau Ances, Jeffrey Burns, H. Diana Rosas, Florence Lai, Sharon Krinsky Mchale, Joseph H. Lee, Frederick A. Schmitt, Jordan Harp, Ira T. Lott, Shahid Zaman, Lauren T. Ptomey

Neurology Faculty Publications

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS. METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (n = 82, mean age = 39.9 ± 8.5 years, 97.6% White race) were age- and sex-matched to participants without CHD (n = 82, mean age = 40.5 ± 8.1 years, 98.8% White race). Cognitive assessments and Centiloid load (CL) (positron …

Plasma P-Tau217 And Apoe Genotype, Ann M. Stowe, Bilal Kahn, Ali Ballesteros, Monique Cortez, Linda S. Hynan, Victoria Cantrell, Indu Raman, Guangchun Chen, Eric D. Vidoni, Ellen Binder, Jeffrey Burns, Jeffrey N. Keller, Diana R. Kerwin, Tristyn Hall, Pavel Yanev, Wanpen Vongapatanasin, David C. Zhu, Norman Scheel, C. Munro Cullum, Rong Zhang, Dwight C. German

Neurology Faculty Publications

Introduction: Plasma phosphorylated tau (p-tau)217 levels and apolipoprotein E (APOE) ε4 genotype are used for prodromal identification of individuals at high risk for dementia. We used baseline samples from cognitively normal subjects in the Risk Reduction for Alzheimer's Disease (rrAD) clinical trial (NCT02913664) to investigate the relationship between these two markers in older adults with additional vascular risk factors. Methods: We measured APOE genotype, plasma p-tau217, and standard neuroimaging metrics in 400 rrAD participants, aged 60 to 84 years, with sedentary lifestyle, hypertension, and hypercholesterolemia. Results: Plasma p-tau217 was 57% higher in subjects with at least one APOE ε4 allele, …

Impact Of Covid-19 Positive Status On Outcome For Individuals With Stroke Treated In Acute Inpatient Rehabilitation, Amy Ziems, Christopher J. Mclouth, Nicholas Elwert, Elissa Charbonneau, Joseph Stillo, Susan Mcdowell

Neurology Faculty Publications

Background: Stroke, whether or not accompanied by concurrent COVID-19 infection, has been associated with varying acute care outcomes, with patients who are COVID-19 positive typically faring worse. This study aims to explore the functional outcomes of patients with stroke —with and without simultaneous COVID-19 infection—who survived their acute care stay and progressed to acute inpatient rehabilitation (IRF). Objectives: To identify differences in sociodemographic factors, medical complexity, and rehabilitation outcomes from an IRF stay between patients with stroke with concurrent COVID-19 and those without. Design: A retrospective, observational cohort study using electronic medical records (EMR) data. Setting: EMR data from 138 …

Hyperacute Interleukin-1Β Production And Neutrophil Extracellular Trap Formation In The Cerebral Circulation Of Stroke Patients With Large Vessel Occlusion, Justine Münsterberg, Caspar Brekenfeld, Hanna Englert, Marius Piepke, Regine J. Dress, Martin Oertel, Tina Fischer, Romy Hackbusch, Mingming Zha, Haodi Cai, Christian Casar, Ines S. Schädlich, Leo Winter, Alina Jander, Karoline Degenhardt, Maxim Bester, Fabian Flottmann, Uta Hanning, Brigitte Holst, Anna Worthman, Johanna Hiefner, Berenike Rutz, Eckhard Schlemm, Götz Thomalla, Bettina H. Clausen, Ann M. Stowe, Immo Prinz, Thiruma V. Arumugam, Markus Glatzel, Thomas Renné, Jens Fiehler, Eva Tolosa

Neurology Faculty Publications

Objective: Cerebral ischemia remains a major cause of disability, and the contribution of the hyperacute immune response is increasingly recognized. The aim of this study was to investigate the local inflammatory response in the affected brain of stroke patients with large vessel occlusion during the hyperacute phase of stroke. Methods: To decipher the role of myeloid immune cells in stroke-induced inflammation, we performed an unsupervised multiomics analysis of innate immune pathways in ischemic blood obtained directly from the occluded middle cerebral artery in 54 patients undergoing mechanical recanalization. Paired nonischemic arterial blood served as an internal control. Results: Stroke triggered …

Decoding The Human Pbmc Isonome, Patricia Hayes Doyle, Madeline L. Page, J. Anthony Brandon, Bernardo Aguzzoli Heberle, Brendan J. White, Ann Marie Stowe, Mark T.W. Ebbert

Neurology Faculty Publications

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at a level difficult to resolve with bulk or short-read methods. This approach enables isoform-level investigation of cellular diversity and disease mechanisms and definition of cell-types, rather than using genes alone. Using a modified, microfluidic-free PIPseq workflow and computational pipeline adapted for Oxford Nanopore long-read sequencing, we generated the largest long-read single-cell dataset of human peripheral blood mononuclear cells (PBMCs) from a single donor to date, the first with sufficient cell numbers to detect megakaryocytes. This study profiled isoform usage across immune cells, integrating marker expression and …

Post-Approval Study 3-Year Outcomes Of The Neuroform Atlas Stent For The Treatment Of Wide-Necked Intracranial Aneurysms, Brian Jankowitz, Ashutosh P. Jadhav, Bradley Gross, Tudor G. Jovin, Abdulnasser A. Alhajeri, Justin F. Fraser, Ricardo A. Hanel, Eric Sauvageau, Amin Aghaebrahim, Donald Frei, Richard Bellon, David N. Loy, Ajit S. Puri, Adel M. Malek, Ajith J. Thomas, Gabor Toth, Demetrius Klee Lopes, R. Webster Crowley, John Reavey-Cantwell, Eugene Lin, Adnan Siddiqui, Michael J. Alexander, Ahmad Khaldi, Geoffrey P. Colby, Justin M. Caplan, Sudhakar R. Satti, Aquilla S. Turk, Alejandro M. Spiotta, Richard Klucznik, Danial K. Hallam, David Kung, Michael T. Froehler

Neurology Faculty Publications

Introduction The ATLAS trial was a prospective, multicenter, single-arm, investigational device exemption (IDE) study to evaluate the safety and effectiveness of the Neuroform Atlas Stent System for the treatment of widenecked bifurcation aneurysms. This analysis presents the 36-month follow-up data for the anterior and posterior cohorts. Methods Of the 182patients in the IDE anterior cohort, 146 consented to participate in the post-approval study (PAS) and, of the 116patients in the IDE posterior cohort, 101 consented to participate in the PAS. The primary effectiveness endpoint was core laboratory adjudicated (Raymond–Roy 1; RR1) without retreatment or parent artery stenosis (>50%) at …

Critical Discourse Analysis Of Nil Policies: Examining Institutional Control And Economic Opportunities For Division I Football Athletes In Power Four Universities, Allen T. Alvarez

Theses and Dissertations--Educational Policy Studies and Evaluation

The adoption of Name, Image, and Likeness (NIL) policies has redefined the economic landscape of collegiate athletics, expanding opportunities for student-athletes and reshaping institutional authority. This dissertation nvestigates how NIL policy language at Division I universities frames economic possibilities for football student-athletes and sustains systems of governance. Through a Critical Discourse Analysis of policy documents from Power Four and mid-major institutions, this study reveals that NIL participation is persistently conditioned by institutional approval, compliance monitoring, and ambiguous definitions, especially regarding boosters and collectives.

Policy language presents NIL as an opportunity but embeds institutional control through oversight structures. The analysis further …

The Operationalization Of Student Success: How Institutions And Divisions Of Student Affairs Define And Align Non-Academic Student Success With External Accountability Expectations, Madeline N. Trudeau

Theses and Dissertations--Educational Policy Studies and Evaluation

This qualitative multi-case study investigates how higher education institutions and their divisions of student affairs publicly discuss and define non-academic student success through their strategic planning, within the context of external pressures from state legislatures and accrediting bodies. Grounded in Organizational Learning Theory, Transition Theory, and Theory of Student Involvement and Engagement, this study analyzes the alignment and divergence between external policy expectations and internal institutional and divisional strategic plans.

The findings reveal a fundamental tension; while external stakeholders increasingly demand quantifiable outcomes tied to economic productivity - like post-graduate wages and employability metrics - divisions of student affairs continue …

Climate Change Effects On Biomass And Greenhouse Gas Emissions Are Ameliorated By Nontoxic Endophytes In Southeastern Usa Transition Zone Tall Fescue Pastures, Rebecca Kay Mcgrail, Jonathan D. Moore, A. Elizabeth Carlisle, Jim A. Nelson, Rebecca L. Mcculley

Plant and Soil Sciences Faculty Publications

Background: The plant–microbe interaction between tall fescue and its endophyte Epichloë coenophiala can affect ecosystem responses to changing rainfall patterns and increasing temperatures. Endophyte-infected (E+) stands often exhibit improved stress tolerance and differing soil greenhouse gas (GHG) emissions compared to endophyte-free (E−) stands. However, it is unknown if mammalian nontoxic endophyte (NTE) strains introduced into some tall fescue cultivars confer differing stress tolerances or reduce soil GHG emissions.

Methods: We quantified the impact of fescue-NTE symbioses in Jesup and Texoma on biomass and GHG emissions in response to increased temperature (+3°C) and altered precipitation (50% lengthened interval between events) using …

Impacts Of Rotation, Tillage, Cover Cropping, And Drainage On Soil Health In Soybean-Based Cropping Systems, Tatiane Severo Silva, Lindsay Chamberlain Malone, Matthew D. Ruark, Chad D. Lee, David Jordan, Hanna J. Poffenbarger, Herman J. Kandel, Jeremy Ross, John M. Gaska, Joseph G. Lauer, Laura E. Lindsey, Maninder Pal Singh, Mark A. Licht, Michael Plumblee, Rachel A. Vann, Rodrigo Werle, Spyridon Mourtzinis, Seth L. Naeve, Trenton L. Roberts, Shawn P. Conley

Plant and Soil Sciences Faculty Publications

Recent studies highlight conservation management practices as an effective strategy to enhance soil health. However, results vary, particularly regarding which soil health parameters respond most sensitively to these practices. More studies covering a wide range of soil types and climatic conditions are needed to assist farmers in making management decisions on production practices related to soil health. In this study, we collected soil samples (0–15 cm) from 21 (4–50 years) soybean [Glycine max (L.) Merr.]-based cropping systems trials across the United States (US) to assess the impact of management practices on soil health indicators. Soil indicators included wet aggregate stability …

Separation Of Trichothecene Mycotoxins In A Matrix Of Hemp (Cannabis Sativa L.) Seed, And Quantification Of Deoxynivalenol In Hemp Grain Infected With Fusarium Graminearum, Isabelle A. Kagan, Magdalena Ricciardi, Henry S. Smith, Rachel R. Schendel, Robert Pearce, Nicole Gauthier

Plant and Soil Sciences Faculty Publications

Background: Fusarium graminearum, one of the causal agents of ear rot in maize and head blight of cereal grains, also infects hemp (Cannabis sativa L. containing a maximum of 0.3% tetrahydrocannabinol or THC). This fungal pathogen produces trichothecene mycotoxins when it infects maize and cereal grains, but little is known about its production of mycotoxins in hemp. A method was developed to separate mycotoxins deoxynivalenol (DON), 15-acetyldeoxynivalenol (15-ADON), and 3-acetyldeoxynivalenol (3-ADON) in commercial hemp seed and grain (harvested tissue), using high-performance liquid chromatography (HPLC) with ultraviolet detection. Results: In HPLC analysis of commercial hemp seed, DON was separated from matrix …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …

Predicting Self-Administered Biologic Nonadherence In Medicare Fee-For-Service Beneficiaries With Inflammatory Bowel Disease Using Machine Learning Models, Christian Rhudy, Courtney Perry, Cody Bumgardner, Michael J. Wesley, David W. Fardo, Terrence Barrett, Jeffery Talbert

Psychiatry Faculty Publications

BACKGROUND: Nonadherence to self-administered biologic therapies increases risk for disease flares and adverse outcomes in inflammatory bowel disease (IBD). OBJECTIVE: To use machine learning and Medicare fee-for-service claims to create models predictive of medication nonadherence. METHODS: This study included Medicare fee-for-service beneficiaries with at least 2 IBD claims separated by 30 days between 2017 and 2021 and analyzed claims data from 2021. Beneficiaries with missing data or fewer than 3 self-administered biologic dispenses (adalimumab, certolizumab, golimumab, ustekinumab) on different dates in 2021 were excluded. Beneficiary-level nonadherence was defined as a proportion of days covered less than 0.8, and dispenselevel nonadherence …

Health Communication Campaign Performance During The Healing Communities Study, Nicky Lewis, Jennifer Reynolds, Diane Krause, Philip M. Reeves, Jamie Luster, Michael D. Stein, Sharon L. Walsh, Amy Farmer, Michelle R. Lofwall, Monica F. Roberts, Hilary L. Surratt, Brooke N. Crockett, Kara Stephens, Kelli Bursey, Kristin Mattson, Michael D. Slater

Psychiatry Faculty Publications

Background: Research on the effectiveness of digital health campaign strategies is lacking. Understanding performance outcomes is essential for the successful implementation of campaigns. Two studies examined platforms, tactics, and content of digital health campaigns using paid media performance data. Objective: This analysis compared 2 digital advertising methods (social media and banner or display) using click-through rate (CTR) and cost-per-click (CPC) as performance measures. Performance differences by state, community type, message approach, format, and image type were assessed. CTR and CPC served as measures in determining performance differences between social media and banner or display. Methods: This cross-sectional secondary analysis examined …

Positive Developmental Cascades, Melody R. Altschuler, Xiaoran Tong, Punit Shah, Edelyn Verona, Julianne M. Bowling, Robert F. Krueger, Roman Kotov, Jordan H. Mcallister, Michaela Voit, Sachina Paudel, Scott C. Leon, Shashwat Kala, John S. Lyons

Psychiatry Faculty Publications

Background: Strength development in children across a range of psychiatric diagnoses may reduce needs for mental health, social, and functioning support over time. A strength-based adjunct to child and adolescent mental health may foster the developmental context most helpful for achieving desired outcomes with positive developmental cascading effects. Methods: We longitudinally examined changes across 5 years in the Child and Adolescent Needs and Strengths Assessment in 2- to 18-year-old children (N = 30,103) from a public mental health system. Results: First, children who began with a greater number of strengths consistently had fewer support needs, not only at entry but …

Reach Of Community-Selected Strategies To Reduce Opioid-Related Overdose Deaths In The Healing Communities Study, Megan E. Hall, La Shawn Glasgow, Ja Nae Holloway, Rouba A. Chahine, Jill Davis, Miriam T.H. Harris, Hannah K. Knudsen, Jessica L. Neufeld, Emmanuel Oga, David W. Lounsbury, Nasim Sabounchi, Alissa Davis, Marissa Smith, Rachel P. Chase, Sylvia A. Ellison, Judy Harness, Hilary L. Surratt, Sharon L. Walsh, Peace Julie Nakayima, Redonna Chandler

Psychiatry Faculty Publications

Introduction: Despite recent declines, the U.S. opioid overdose crisis persists. The HEALing Communities Study (HCS) aimed to reduce opioid overdose deaths through community-level adoption of evidence-based practices (EBPs), including overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD). This paper describes the reach of OEND and MOUD strategies implemented by the 33 HCS wait-list control communities. Methods: We conducted descriptive statistical analysis of reach data collected from July 2022 through December 2023 to (1) summarize overall EBP implementation and reach and (2) compare the demographic representation of individuals reached to community demographic population estimates. Results: Communities …

The Association Between Naloxone Distribution, Buprenorphine Treatment And Retention And Incident High-Risk Opioid Prescribing With Opioid Overdose Death In Kentucky, Massachusetts, New York And Ohio, United States, Alexander Y. Walley, Debbie M. Cheng, Nathan Vandergrift, Marc Larochelle, Ja Nae Holloway, Jennifer L. Brown, Redonna Chandler, Laura C. Fanucchi, Daniel J. Feaster, Patricia Freeman, Timothy Hunt, Michelle R. Lofwall, Hannah K. Knudsen, Edward V. Nunes, Emmanuel Oga, Douglas R. Oyler, Jeffrey H. Samet, Jennifer Villani, Sharon Walsh, T. John Winhusen

Psychiatry Faculty Publications

Aim: We evaluated whether community-level naloxone distribution, medication for opioid use disorder treatment and retention and incident high-risk opioid prescribing rates were associated with opioid overdose death rates. Design: Observational cohort conducted using 2019 to 2023 community-level data as an exploratory analysis of the HEALing (Helping to End Addiction Long-term®) Communities Study (HCS). Exposures included: (1) community-level naloxone distribution, past 12-months, categorized as ≤1000 units per 100 000 population vs. 1001–3000 units per 100 000 population vs. >3000 units per 100 000 population; (2) individuals treated with buprenorphine per 100 000 adult population in the current quarter; (3) individuals retained …

The Role Of Small Extracellular Vesicles In Modulating Radiation Resistance In H3k27m-Pediatric Diffuse Midline Glioma, Viral Oza

Theses and Dissertations--Molecular and Cellular Biochemistry

Pediatric diffuse midline gliomas with H3K27M alteration (H3K27M-pDMG) are the leading cause of pediatric brain tumor-associated deaths. All H3K27M-pDMG are initially treated with fractionated radiotherapy, the standard of care, and most children succumb to their disease within two years of diagnosis. There are no universally effective chemotherapies and full resection is impossible due to the diffuse nature of the tumor and sensitive location. There has not been a significant clinical advancement in more than 40 years.

Tumors become completely resistant to radiation within the first six months of treatment. The mechanism of radiation resistance is unknown but is thought to …

Colon Cancer In Appalachian Kentucky: Unique Genetic, Microbiome And Obesity Findings In A Cohort Comparison, Zeta Chow, Jinpeng Liu, Daheng He, Chi Wang, Tong Gan, Akila Mansour, Nuha Shaker, Caroline Dravillas, Rebecca Hoyd, Eric B. Durbin, Dana L. Napier, Tianyan Gao, Kurt Schaberg, Lyen Huang, Neli Ulrich, Erin Siegel, Stephen Edge, Linda Cook, Bodour Salhia, Michelle L. Churchman, Jill Kolesar, Daniel Spakowicz, B. Mark Evers, Therese J. Bocklage

Markey Cancer Center Faculty Publications

We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell …

Hexavalent Chromium Promotes Malignant Transformation Via Enhanced Translation Of Suv39h1, Yiwei Gu, Yanan Cao, Qing Ye, Yujing Zhang, Zhishan Wang, Chengfeng Yang, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Hexavalent chromium [Cr(VI)] is a widespread environmental carcinogen linked to lung cancer and other malignancies. Although genetic and epigenetic mechanisms of Cr(VI)-induced carcinogenesis have been extensively investigated, the role of translational control has remained largely unexplored. Here, we show that chronic low-dose Cr(VI) exposure in BEAS-2BR human bronchial epithelial cells activates eIF4E-driven cap-dependent translation through mTORC1-mediated phosphorylation and inactivation of the translational repressor 4E-BP1. Pharmacological inhibition of this pathway markedly suppresses Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like properties, and DNA damage. Comparable inhibitory effects are observed following raptor knockdown, which disrupts mTORC1, or expression of a constitutively active non-phosphorylatable …