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Articles 1591 - 1620 of 52414

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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 Dec 2025

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 …

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Nonfatal Injury Emergency Department Visits And Inpatient Hospitalizations Among Persons Under Age 65 With An Intellectual And Developmental Disability Or Deaf Or Hard Of Hearing Disability, Terry L. Bunn, Jacqueline Seals, Dana Quesinberry, Alaina Murphy, Julia F. Costich Dec 2025

Nonfatal Injury Emergency Department Visits And Inpatient Hospitalizations Among Persons Under Age 65 With An Intellectual And Developmental Disability Or Deaf Or Hard Of Hearing Disability, Terry L. Bunn, Jacqueline Seals, Dana Quesinberry, Alaina Murphy, Julia F. Costich

Epidemiology and Environmental Health Faculty Publications

Background: Vulnerable populations at risk of injury include persons with intellectual and developmental disabilities (IDD), and persons who are deaf or hard of hearing (DHH). The purpose of this study was to describe and compare emergency department and inpatient hospitalization (ED + IP) injury rates and rate ratios by injury type among persons under age 65 with IDD or with DHH to those without IDD or DHH. Methods: This is a descriptive population-based retrospective cross-sectional study of injuries among patients under the age of 65 with an IDD disability or a DHH disability using Kentucky ED + IP discharge datasets …

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Patterns And Characteristics Of Gabapentin Use Among Medicare Beneficiaries, Gyeon Oh, Daniela C. Moga, Patricia R. Freeman, Erin L. Abner Dec 2025

Patterns And Characteristics Of Gabapentin Use Among Medicare Beneficiaries, Gyeon Oh, Daniela C. Moga, Patricia R. Freeman, Erin L. Abner

Epidemiology and Environmental Health Faculty Publications

Background: Gabapentin is increasingly prescribed to older adults, yet prescribing patterns and characteristics of gabapentin initiators remain unclear. Methods: We conducted a retrospective cohort study of gabapentin initiators using a random sample of age-eligible fee-for-service Medicare beneficiaries (2012–2021) enrolled in Parts A, B, and D. Gabapentin initiators were identified from pharmacy claims. We required 180 days of continuous enrollment (washout period) prior to initiation (index date) for inclusion. We analyzed demographics, healthcare utilization within 3 months of initiation, chronic conditions, medication history during washout period, and patterns of gabapentin use. Subgroup analyses compared initiators by duration of continuous gabapentin use …

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Preferences For Harm Reduction Vending Machine Design Among Rural People Who Use Drugs, April M. Young, Tasfia Jahangir, Susan Westneat, Chelsi Cheatom, Amanda Fallin-Bennett, Laura C. Fanucchi, Patricia R. Freeman, Jennifer R. Havens, Hannah K. Knudsen, Kathryn E. Mccollister, Susannah Stitzer, Jack Stone, Peter Vickerman, Melvin D. Livingston Dec 2025

Preferences For Harm Reduction Vending Machine Design Among Rural People Who Use Drugs, April M. Young, Tasfia Jahangir, Susan Westneat, Chelsi Cheatom, Amanda Fallin-Bennett, Laura C. Fanucchi, Patricia R. Freeman, Jennifer R. Havens, Hannah K. Knudsen, Kathryn E. Mccollister, Susannah Stitzer, Jack Stone, Peter Vickerman, Melvin D. Livingston

Epidemiology and Environmental Health Faculty Publications

Globally, harm reduction vending machines (HRVMs) have been used for decades to dispense safe injection equipment and other supplies to people who use drugs (PWUD). However, HRVMs have only recently scaled up in the U.S. and few operate in rural settings. This study describes preferences for HRVM design among rural PWUD in two Appalachian Kentucky communities. Peer-referral and outreach were used to recruit participants (n = 731). Eligibility criteria were ≥ 18 years, residing in the target counties, and having used any drug (excluding alcohol, cannabis, and tobacco) to get high within 6 months. Interviewer-administered questionnaires elicited data on behavioral/demographic …

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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 Dec 2025

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 …

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Prospective Cohort Study Of Fentanyl Test Strip Use And Distribution In Three States, Janet E. Childerhose, Kitty Gelberg, Rachel Vickers-Smith, Megan E. Dzurec, Emmanuel Oga, Mallory Harris, Rachel Caspar, Denise C. Babineau, Megan E. Hall, Beth S. Linas, Katherine E. Marks, Amanda Fallin-Bennett, Laura C. Fanucchi, Louisa Gilbert, James L. David, Mary Russo, Kathryn E. Lancaster, Soledad Fernandez, Michael Konstan, Redonna K. Chandler, Carter Roeber, Jennifer Villani, Rebecca D. Jackson, Bridget Freisthler, Sharon L. Walsh, Nabila El-Bassel Dec 2025

Prospective Cohort Study Of Fentanyl Test Strip Use And Distribution In Three States, Janet E. Childerhose, Kitty Gelberg, Rachel Vickers-Smith, Megan E. Dzurec, Emmanuel Oga, Mallory Harris, Rachel Caspar, Denise C. Babineau, Megan E. Hall, Beth S. Linas, Katherine E. Marks, Amanda Fallin-Bennett, Laura C. Fanucchi, Louisa Gilbert, James L. David, Mary Russo, Kathryn E. Lancaster, Soledad Fernandez, Michael Konstan, Redonna K. Chandler, Carter Roeber, Jennifer Villani, Rebecca D. Jackson, Bridget Freisthler, Sharon L. Walsh, Nabila El-Bassel

Epidemiology and Environmental Health Faculty Publications

Background: The Stay Safe Study is the first observational prospective cohort study investigating fentanyl test strip (FTS) use by people who use drugs (PWUD) and distribution by community organizations that provide harm reduction services (e.g., naloxone distribution) in three states (Kentucky, New York, and Ohio). The purpose of this paper is to describe the study design, along with implementation successes and challenges. A related goal is to provide recommendations and encourage researchers to undertake multi-state and multilevel studies of FTS use and distribution. Methods: The Stay Safe Study has one primary, five secondary, and three exploratory objectives. From May-December 2023, …

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Referrals And Utilization Of Diabetes Self-Management Education And Support (Dsmes) Among Patients With Type 1 And Type 2 Diabetes At A Regional Medical Center In Kentucky, Omer Atac, George C. Bryant, William B. Burrows, Kory R. Heier, James W. Keck, Key C. Douthitt, Mary E. Lacy Dec 2025

Referrals And Utilization Of Diabetes Self-Management Education And Support (Dsmes) Among Patients With Type 1 And Type 2 Diabetes At A Regional Medical Center In Kentucky, Omer Atac, George C. Bryant, William B. Burrows, Kory R. Heier, James W. Keck, Key C. Douthitt, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

Background: The goal of this study was to examine referral and attendance patterns for diabetes self-management education and support (DSMES) among patients with both type 1 (T1D) and type 2 diabetes (T2D) at a regional medical center in Kentucky, and to identify demographic and clinical factors associated with these outcomes. Methods: We analyzed electronic health records of adults with diabetes (n = 10,587; n = 817 with T1D and n = 9,770 with T2D) who received care from 1/1/2016-12/31/2019 at University of Kentucky HealthCare. We compared DSMES referral and attendance rates by various demographic and clinical factors and used logistic …

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Using The Practical, Robust Implementation And Sustainability Model To Identify Implementation Determinants Of A Statewide Diabetes Learning Collaborative In Kentucky, Aaron J. Kruse-Diehr, Borsika A. Rabin, Jessica Elliott, Vance Drakeford, Laura Wright, Brent Mckune, Russell E. Glasgow, Key C. Douthitt, James W. Keck, Mary E. Lacy Dec 2025

Using The Practical, Robust Implementation And Sustainability Model To Identify Implementation Determinants Of A Statewide Diabetes Learning Collaborative In Kentucky, Aaron J. Kruse-Diehr, Borsika A. Rabin, Jessica Elliott, Vance Drakeford, Laura Wright, Brent Mckune, Russell E. Glasgow, Key C. Douthitt, James W. Keck, Mary E. Lacy

Epidemiology and Environmental Health Faculty Publications

Background: Prevalence of type 2 diabetes (T2D) in Kentucky is among the highest in the United States. Diabetes self-management education and support (DSMES) is an evidence-based intervention that teaches people living with T2D to self-manage their disease but is underutilized in Kentucky despite being available free-of-charge to residents of every county. One promising strategy to improve DSMES utilization is clinic participation in a learning collaborative, wherein participants undertake small tests of change to improve the referral process. The purpose of this study was to identify determinants related to successful implementation of the learning collaborative, as well as perceived progress on …

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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 Dec 2025

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 …

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Willingness To Receive Medication For Opioid Use Disorder (Moud), Hannah K. Knudsen, Maria Rockett, Carrie B. Oser Dec 2025

Willingness To Receive Medication For Opioid Use Disorder (Moud), Hannah K. Knudsen, Maria Rockett, Carrie B. Oser

Sociology Faculty Publications

Background: Medications for opioid use disorder (MOUD, i.e., buprenorphine, methadone, naltrexone) save lives, but many individuals are unwilling to receive MOUD treatment. Few longitudinal studies have examined whether social network support for MOUD is related to willingness to receive MOUD. Methods: Egocentric network data were collected from 393 adults with OUD who were incarcerated in 14 Kentucky prisons; follow-up data were collected about six months post-release. For each named alter, participants (egos) reported on perceived alters’ support for buprenorphine, methadone, and naltrexone at baseline and follow-up; baseline network scores were averaged into a network support for MOUD score and a …

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Overdose Education And Naloxone Distribution In Jails, Timothy Hunt, Carrie B. Oser, Peter D. Friedmann, Nicole Mack, Peter Balvanz, Bridget Freisthler, Redonna K. Chandler, Karli Hochstatter, Daniel R. Harris, La Shawn Glasgow, Lauren D’Costa, Mary R. Russo, Barry Eggleston, Arnie Aldridge, Paul Bellair, Allyson G. Cogan, James L. David, Nabila El-Bassel, Dawn Goddard-Eckrich, Steve Gomori, Holly Hagan, Steve Hanson, Ja Nae Holloway, Elizabeth N. Kinnard, Charlie Knott, Michael W. Konstan, Sharon L. Walsh, Patricia A. Lebaron Dec 2025

Overdose Education And Naloxone Distribution In Jails, Timothy Hunt, Carrie B. Oser, Peter D. Friedmann, Nicole Mack, Peter Balvanz, Bridget Freisthler, Redonna K. Chandler, Karli Hochstatter, Daniel R. Harris, La Shawn Glasgow, Lauren D’Costa, Mary R. Russo, Barry Eggleston, Arnie Aldridge, Paul Bellair, Allyson G. Cogan, James L. David, Nabila El-Bassel, Dawn Goddard-Eckrich, Steve Gomori, Holly Hagan, Steve Hanson, Ja Nae Holloway, Elizabeth N. Kinnard, Charlie Knott, Michael W. Konstan, Sharon L. Walsh, Patricia A. Lebaron

Sociology Faculty Publications

Background: Opioid-related overdose is the leading cause of mortality among individuals recently released from incarceration in the U.S. Naloxone is an FDA-approved opioid antagonist medication designed to rapidly reverse opioid overdose. Despite evidence of its acceptability and effectiveness at reducing the risk of opioid overdose death after release from incarceration, only an estimated 25% of US jails provide naloxone upon release. This study examines the effectiveness of the HEALing Communities Study (HCS) Communities That HEAL (CTH) intervention on enhancing access to overdose education and naloxone distribution (OEND) in participating jails in Kentucky, New York, Massachusetts, and Ohio. Methods: Communities were …

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The Importance Of Contextually Specific Support Relationships In Implementing Programs To Link People To Medication For Opioid Use Disorder (Moud) Treatment During Reentry From County Jails, Margaret Mcgladrey, Marisa Booty, Susannah Stitzer, Hannah K. Knudsen, Sharon L. Walsh, Michael Goetz, Hallie Mattingly, Michelle Lofwall, Laura Fanucchi, Devin Oller, Amanda Fallin-Bennett, Carrie B. Oser Dec 2025

The Importance Of Contextually Specific Support Relationships In Implementing Programs To Link People To Medication For Opioid Use Disorder (Moud) Treatment During Reentry From County Jails, Margaret Mcgladrey, Marisa Booty, Susannah Stitzer, Hannah K. Knudsen, Sharon L. Walsh, Michael Goetz, Hallie Mattingly, Michelle Lofwall, Laura Fanucchi, Devin Oller, Amanda Fallin-Bennett, Carrie B. Oser

Sociology Faculty Publications

Background: This study uses the Practical, Robust, Implementation, and Sustainability Model (PRISM) and Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model to describe how features of jail contexts are associated with the number of people linked to medication for opioid use disorder (MOUD) and sustainment of jail linkage programs implemented in Wave 1 of the HEALing Communities Study in Kentucky (HCS-KY) from 2021 to 22. The HCS-KY is part of a parallel-group, cluster-randomized wait-list controlled trial examining the effects of supporting wide-scale implementation of evidence-based practices to reduce opioid overdose deaths. One strategy involved implementation of MOUD linkage programs within …

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Exclusivity In Early Maya Monumentality, Scott R. Hutson, Mario Zimmermann, Iliana Ancona Aragón Dec 2025

Exclusivity In Early Maya Monumentality, Scott R. Hutson, Mario Zimmermann, Iliana Ancona Aragón

Anthropology Faculty Publications

Datasets from around the world suggest that people completed early monumental construction projects without long-term structures of hierarchy or authority. In the Maya area, some of the first monuments produced by semisedentary societies, such as those at Yaxuna and Ceibal, were built in the absence of substantial social inequality. The focus of these monuments was a relatively inclusive plaza. This article presents evidence of an eighth-century BC monumental construction at Ucí, another site that was probably not fully sedentary. At Ucí, however, the first large architecture is not inclusive. Structure 14sub5 lacks a front stairway, separating people in the plaza …

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Petrology And Geochemistry Of The Middle Pennsylvanian (Langsettian) Clintwood Coalbed, Pike County, Kentucky, James C. Hower, Cortland F. Eble, Shelley D. Hopps, Tonya D. Morgan, Vivian A. Edwards Dec 2025

Petrology And Geochemistry Of The Middle Pennsylvanian (Langsettian) Clintwood Coalbed, Pike County, Kentucky, James C. Hower, Cortland F. Eble, Shelley D. Hopps, Tonya D. Morgan, Vivian A. Edwards

Earth and Environmental Sciences Faculty Publications

The Middle Pennsylvanian, Langsettian sub-stage Clintwood coal, along with its correlatives, was one of the more important energy resources in eastern Kentucky. The coal thickens from the NE-SW-trending Belfry anticline in central Pike County to the southeast, towards the Virginia-Kentucky border. Much of the thickness increase is in the bright lithotypes below a dull lithology. The bright lithologies transition from a bright clarain + vitrain + fusain lithology to a clarain + fusain lithology to the southeast. Half of the lithotypes in the three analyzed sections exceed 1000-µg/g Rare earth elements + Y + Sc (REYSc) (ash basis). The La …

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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 Dec 2025

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: …

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Direct Measurement Of Mavacamten And Deoxyatp Perturbation Of The Srx/Drx Ratio In Porcine Cardiac Myofibrils Using A Simple, Accessible And Multiplexed Approach, Matvey Pilagov, Ateeqa Naim, Kenneth S. Campbell, Thomas Kampourakis, Michael A. Geeves, Neil M. Kad Dec 2025

Direct Measurement Of Mavacamten And Deoxyatp Perturbation Of The Srx/Drx Ratio In Porcine Cardiac Myofibrils Using A Simple, Accessible And Multiplexed Approach, Matvey Pilagov, Ateeqa Naim, Kenneth S. Campbell, Thomas Kampourakis, Michael A. Geeves, Neil M. Kad

Physiology Faculty Publications

Cardiac muscle adapts to varying physiological demands by modulating the number of active myosin II motors available for contraction. These motors are organized into thick filaments in the sarcomere and generate force through an ATP-dependent interaction with thin filaments that contain actin. To conserve energy, when demand is low myosin can occupy the super-relaxed (SRX) state, which acts as a reserve. Here, we build upon the earlier studies to quantify the size of this cardiac reserve using fluorescence imaging of Cy3-ATP directly in myofibrils. This approach employs a pulse-chase method and exploits the high permeability of isolated myofibrils to monitor …

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Apoe4 To Apoe2 Allelic Switching In Mice Improves Alzheimer’S Disease-Related Metabolic Signatures, Neuropathology And Cognition, Lesley R. Golden, Dahlia S. Siano, Isaiah O. Stephens, Steven M. Maclean, Kai Saito, Georgia L. Nolt, Jessica L. Funnell, Akhil V. Pallerla, Sangderk Lee, Cathryn Smith, Jing Chen, Haining Zhu, Clairity Voy, Callie M. Whitus, Gabriela Hernandez, Brandon C. Farmer, Kumar Pandya, Dale O. Cowley, Shannon L. Macauley, Scott M. Gordon, Josh M. Morganti, Lance A. Johnson Dec 2025

Apoe4 To Apoe2 Allelic Switching In Mice Improves Alzheimer’S Disease-Related Metabolic Signatures, Neuropathology And Cognition, Lesley R. Golden, Dahlia S. Siano, Isaiah O. Stephens, Steven M. Maclean, Kai Saito, Georgia L. Nolt, Jessica L. Funnell, Akhil V. Pallerla, Sangderk Lee, Cathryn Smith, Jing Chen, Haining Zhu, Clairity Voy, Callie M. Whitus, Gabriela Hernandez, Brandon C. Farmer, Kumar Pandya, Dale O. Cowley, Shannon L. Macauley, Scott M. Gordon, Josh M. Morganti, Lance A. Johnson

Physiology Faculty Publications

Compared to individuals carrying two copies of the ε4 allele of apolipoprotein E (APOE), ε2 homozygotes have an approximate 99% reduction in late-onset Alzheimer’s disease (AD) risk. Here we develop a knock-in model that allows for an inducible ‘switch’ between risk and protective alleles (APOE4s2). Gene expression and proteomic analyses confirm that APOE4s2 mice synthesize E4 at baseline and E2 after tamoxifen administration. A whole-body allelic switch results in a metabolic profile resembling E2/E2 humans and drives AD-relevant alterations in the lipidome and single-cell transcriptome, particularly in astrocytes. Finally, when crossed to the 5xFAD background, astrocyte-specific E4 to E2 switching …

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Insulin Resistance, Cognition, And Functional Brain Network Topology In Older Adults With Obesity, Clayton C. Mcintyre, Robert G. Lyday, Yixin Su, Barbara Nicklas, Sean L. Simpson, Gagan Deep, Shannon L. Macauley, Christina E. Hugenschmidt Dec 2025

Insulin Resistance, Cognition, And Functional Brain Network Topology In Older Adults With Obesity, Clayton C. Mcintyre, Robert G. Lyday, Yixin Su, Barbara Nicklas, Sean L. Simpson, Gagan Deep, Shannon L. Macauley, Christina E. Hugenschmidt

Physiology Faculty Publications

Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral insulin resistance (PIR) and neuronal insulin signaling abnormalities (NISAs) relate to executive function and functional brain network topology. Older adults (n = 71) with obesity but without type 2 diabetes were included. PIR was quantified by HOMA2-IR. NISAs were quantified according to an established neuron-derived small-extracellular-vesicle-based metric, R. An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1–5, and functional brain networks generated from resting-state functional magnetic resonance imaging data were outcomes in analyses. We used general linear …

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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 Dec 2025

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 …

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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 Dec 2025

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 …

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Right Ventricular Vulnerability, Cheavar A. Blair, Bryana M. Levitan, Tori Brown, Nakeya Dewaswala, Amit Arbune Dec 2025

Right Ventricular Vulnerability, Cheavar A. Blair, Bryana M. Levitan, Tori Brown, Nakeya Dewaswala, Amit Arbune

Physiology Faculty Publications

Background: Right ventricular (RV) dysfunction may arise from several reasons, including pulmonary embolism (PE) or cancer therapy-related cardiotoxicity. PE elevates pulmonary pressures, straining the RV, which can cause dysfunction, while anthracyclines, though primarily recognized for impacting the left ventricle, can also impair the RV. The interplay between these conditions remains poorly understood, particularly the RV’s susceptibility to anthracycline cardiotoxicity after recovering from PE-induced strain. This case study highlights a patient who initially had PE-related RV dysfunction; however, data from three medical centers revealed RV recovery after PE, followed by RV failure, with subsequent left ventricular (LV) failure after chemotherapy. Case …

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Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B. Graf, Yuriko Katsumata, Jessica J. Moorleghen, Chen Zhang, Yanming Li, Scott A. Lemaire, Ying H. Shen, Hong S. Lu, Alan Daugherty, Hisashi Sawada Dec 2025

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B. Graf, Yuriko Katsumata, Jessica J. Moorleghen, Chen Zhang, Yanming Li, Scott A. Lemaire, Ying H. Shen, Hong S. Lu, Alan Daugherty, Hisashi Sawada

Physiology Faculty Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

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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 Dec 2025

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 …

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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 Dec 2025

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).

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Neurotensin Promotes Hepatic Steatosis By Regulating Lipid Uptake And Mitochondrial Adaptation In Hepatocytes, Moumita Banerjee, Jun Song, Baoxiang Yan, Haoming Wu, Shaghayegh Norouzi, Tomoko Sengoku, Savita Sharma, Teresa W.M. Fan, Eun Lee, Daheng He, Chi Wang, Jinpeng Liu, Timothy M. Schmitt, Tianyan Gao, Heidi L. Weiss, Jing Li, B. Mark Evers Dec 2025

Neurotensin Promotes Hepatic Steatosis By Regulating Lipid Uptake And Mitochondrial Adaptation In Hepatocytes, Moumita Banerjee, Jun Song, Baoxiang Yan, Haoming Wu, Shaghayegh Norouzi, Tomoko Sengoku, Savita Sharma, Teresa W.M. Fan, Eun Lee, Daheng He, Chi Wang, Jinpeng Liu, Timothy M. Schmitt, Tianyan Gao, Heidi L. Weiss, Jing Li, B. Mark Evers

Surgery Faculty Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disease characterized by hepatic steatosis. Mitochondrial dysfunction resulting in the incomplete digestion of surplus fat is one of the key factors that lead to hepatic steatosis but the reason for this remains unclear. We investigated the role of neurotensin (NTS), a gut hormone, in inducing maladaptive fat metabolism in steatotic liver. We identify CD36 and PGC1α, two critical drivers of MASLD, as direct NTS signaling targets in the liver. NTS upregulates CD36, a free fatty acid receptor, in hepatocytes and promotes long chain lipid uptake. Conversely, NTS inhibits PGC1α, which acts …

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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 Dec 2025

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 …

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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 Dec 2025

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 …

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Barriers And Facilitating Factors For Covid-19 Vaccination In Rural Appalachia, Kathryn M. Cardarelli, Rachel Gillespie, Anna Goodman Hoover, Diane B. Francis, Marc T. Kiviniemi Dec 2025

Barriers And Facilitating Factors For Covid-19 Vaccination In Rural Appalachia, Kathryn M. Cardarelli, Rachel Gillespie, Anna Goodman Hoover, Diane B. Francis, Marc T. Kiviniemi

Epidemiology and Environmental Health Faculty Publications

Background: Since the onset of the pandemic, COVID-19 mortality has disproportionately impacted populations impacted by health inequities. This study aimed to identify the barriers and facilitators to COVID-19 vaccination uptake in Appalachian Kentucky as a first step to developing vaccination interventions. Methods: Key informant interviews were conducted with 36 community leaders in 14 Appalachian Kentucky counties from January-June 2023. Interviews focused on leaders’ perspectives about their community’s COVID-19 experiences, community impacts of the pandemic, and vaccine facilitators and barriers in their communities. Iterative inductive-deductive coding was used to characterize responses. Results: There were barriers and facilitators at multiple levels of …

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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 Dec 2025

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 …

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Integrating Eem Fluorescence Spectroscopy With Machine And Deep Learning Models For Multi-Output Prediction Of Fish Freshness, Yanwei Fan, Zengtao Ji, Chuanheng Sun, Daming Xu, Xinting Yang, Ce Shi, Hongbing Fan Dec 2025

Integrating Eem Fluorescence Spectroscopy With Machine And Deep Learning Models For Multi-Output Prediction Of Fish Freshness, Yanwei Fan, Zengtao Ji, Chuanheng Sun, Daming Xu, Xinting Yang, Ce Shi, Hongbing Fan

Animal and Food Sciences Faculty Publications

A precise and real-time assessment of the freshness of aquatic products during storage can effectively reduce economic losses and food safety problems. This study developed a novel multi-output freshness monitoring model integrating excitation-emission matrix (EEM) fluorescence spectroscopy with two machine learning (ML) and one deep learning (DL) approach to simultaneously predict freshness indices and classify freshness stages. We Utilized bighead carp (Hypophthalmichthys nobilis) andrainbow trout (Oncorhynchus mykiss), to predict TVB-N, K value, and TVC freshness indices via PCA-RF regression, achieving R² = 0.85-0.98 and RMSE = 0.23-3.63 significantly outperforming PARAFAC-SVR/RF and PCA-SVR; classify freshness into fresh, sub_fresh, and rot stages …

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