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Full-Text Articles in Medical Specialties

Deaths Of Despair Among Cancer Survivors In Rural/Urban Appalachia (2000-2022), Jason Semprini, Anders Erickson, Nosa Osazuwa-Peters Aug 2026

Deaths Of Despair Among Cancer Survivors In Rural/Urban Appalachia (2000-2022), Jason Semprini, Anders Erickson, Nosa Osazuwa-Peters

Journal of Appalachian Health

Introduction: Rising deaths of despair (premature deaths from suicide, overdose, alcohol, and violence) in adults under age 65 persist across the United States, especially in Appalachia. People diagnosed with cancer may face elevated risks of such deaths due to pain, psychosocial distress, and financial hardship.

Purpose: Deaths of despair trends were compared among adults with cancer across Appalachian and non-Appalachian regions, stratified by sex and rurality.

Methods: Analyzing SEER-21 Incidence-Based Mortality data (2000–2022), deaths caused by suicide, cirrhosis of the liver, or accidents (includes overdose) were identified among adults aged 20–64 years. Annual mortality rates per 100,000 total population were …


Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith Feb 2026

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …


A Novel Less Invasive Single Port Pulsatile Ventricular Assist Device, Li Li, Jinsong Chen, Zhongjiang Zhuang, Stephen Topaz, Masashi Kawabori, Joseph B. Zwischenberger, Cherry Ballard-Croft, Dongfang Wang Jan 2026

A Novel Less Invasive Single Port Pulsatile Ventricular Assist Device, Li Li, Jinsong Chen, Zhongjiang Zhuang, Stephen Topaz, Masashi Kawabori, Joseph B. Zwischenberger, Cherry Ballard-Croft, Dongfang Wang

Surgery Faculty Publications

A less invasive paracorporeal single port pulsatile ventricular assist device (sppVAD) was developed for cardiogenic shock. This compact sppVAD includes a valved single lumen cannula (VSLC), valveless single port diaphragm displacement pump (spDDP), and portable console. A 33/27 Fr VSLC was fabricated for mock loop testing, a 28/25 Fr VSLC was made for 6 hours sheep testing (n = 5, 44–52 kg), and valveless spDDP with portable console was made. The sppVAD (33/27 Fr VSLC) achieved 6.2 L/min flow in mock loop. In sheep, the 28/25 Fr VSLC was inserted without cardiopulmonary bypass from apex to ascending aorta within 1 …


Inhibition Of Fatty Acid Synthase Enhances Therapeutic Efficacy And Delays Acquired Resistance To Braf-Targeted Therapy In Colorectal Cancer, Mariah E. Geisen, Elisane W. Tessmann, Courtney O. Kelson, Daheng He, Chi Wang, Abu Saleh Mosa Faisal, Ellen J. Beswick, Yasmine Baca, Stephanie Rock, Jill M. Kolesar, Yekaterina Y. Zaytseva Jan 2026

Inhibition Of Fatty Acid Synthase Enhances Therapeutic Efficacy And Delays Acquired Resistance To Braf-Targeted Therapy In Colorectal Cancer, Mariah E. Geisen, Elisane W. Tessmann, Courtney O. Kelson, Daheng He, Chi Wang, Abu Saleh Mosa Faisal, Ellen J. Beswick, Yasmine Baca, Stephanie Rock, Jill M. Kolesar, Yekaterina Y. Zaytseva

Toxicology and Cancer Biology Faculty Publications

The presence of BRAF V600E mutations is associated with poor prognosis in colorectal cancer (CRC). Although the FDA-approved combination of encorafenib and cetuximab provides clinical benefit in this population, only 22% of patients respond and most eventually develop resistance. This study investigated the mechanisms of resistance to PLX8394, a second-generation BRAF inhibitor. Using primary and established BRAF V600E CRC cells, we show that the development of resistance to PLX8394 results in cross-resistance of cells to encorafenib. Moreover, the acquired resistance is associated with increased proliferation, invasion, and upregulation of lipid metabolism, including increased expression of fatty acid synthase (FASN), a …


Twenty-First Century Data Systems: Evolving Cancer Registries To A Learning Health System, Peter P. Yu, W. Scott Campbell, Eric B. Durbin, Lawrence N. Shulman, Jeremy L. Warner Jan 2026

Twenty-First Century Data Systems: Evolving Cancer Registries To A Learning Health System, Peter P. Yu, W. Scott Campbell, Eric B. Durbin, Lawrence N. Shulman, Jeremy L. Warner

Markey Cancer Center Faculty Publications

Introduction: Oncology is a data-rich environment reflecting the increasing incidence of cancer in the US aging population, transformation of cancer into a chronic disease due to advances in treatment, and the emergence of new data categories such as genomics. Concomitantly, healthcare systems are challenged to meet regulatory and voluntary reporting of cancer data to support government, quality certification, research and strategic partnership needs.

Materials and Methods: The National Academies of Science, Engineering, and Medicine organized a workshop entitled “Enabling 21st-century applications for cancer surveillance through enhanced registries and beyond” with representation from NCI Comprehensive Cancer Centers, oncology and medical informatics …


Clopidogrel Versus Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Updated Meta- Analysis Of 162,829 Patients, Mohammed A. Elbahloul, Ahmed Mansour, Amr Galal, Walaa M. Moawad, Manar Khaled, Ahmed Wahdan Kasem, Eman E. Labeeb, Islam Y. Elgendy Jan 2026

Clopidogrel Versus Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Updated Meta- Analysis Of 162,829 Patients, Mohammed A. Elbahloul, Ahmed Mansour, Amr Galal, Walaa M. Moawad, Manar Khaled, Ahmed Wahdan Kasem, Eman E. Labeeb, Islam Y. Elgendy

Gill Heart & Vascular Institute Faculty Publications

Background: Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains a cornerstone for preventing ischemic events; however, the optimal long-term single antiplatelet therapy after completion of DAPT remains unclear. We aimed to compare clopidogrel and aspirin monotherapy after completion of the standard duration of DAPT.

Methods: A systematic search was conducted on PubMed, Scopus, Cochrane Library, and Web of Science from inception to April 2025. We included randomized clinical trials and observational studies that compared aspirin versus clopidogrel monotherapy after completion of standard-duration DAPT. The primary and co-primary outcomes were major adverse cardiovascular events (MACE) and major bleeding, respectively. …


Colchicine Among Patients With Acute Coronary Syndrome: A Meta‑Analysis Of Randomized Trials, Mohamed Hamed, Sheref A. Mohamed, Mohamed Abdelazeem, Eric Lieberman, Abdelrahman Ali, Dharam J. Kumbhani, Anthony Bavry, Hani Jneid, Islam Y. Elgendy, Ayman Elbadawi Jan 2026

Colchicine Among Patients With Acute Coronary Syndrome: A Meta‑Analysis Of Randomized Trials, Mohamed Hamed, Sheref A. Mohamed, Mohamed Abdelazeem, Eric Lieberman, Abdelrahman Ali, Dharam J. Kumbhani, Anthony Bavry, Hani Jneid, Islam Y. Elgendy, Ayman Elbadawi

Gill Heart & Vascular Institute Faculty Publications

Introduction: Prior trials evaluating the benefit of colchicine in patients with acute coronary syndrome (ACS) have yielded mixed results. Hence, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of colchicine after ACS.

Methods: We performed an electronic search of MEDLINE, Embase, and Cochrane databases through November 2024 for studies comparing colchicine with placebo after ACS. Our study’s primary outcome was major adverse cardiac events (MACE).

Results: Our final analysis included five RCTs with 12,979 patients with a mean follow-up of 26.6 months. The weighted mean age was 59.8 years. Colchicine was associated with a modest …


Dark And Camouflaged Genomic Regions Remain Challenging In Chm13, Mark E. Wadsworth, Madeline L. Page, Bernardo Aguzzoli Heberle, Justin B. Miller, Cody J. Steely, Mark T. W. Ebbert Jan 2026

Dark And Camouflaged Genomic Regions Remain Challenging In Chm13, Mark E. Wadsworth, Madeline L. Page, Bernardo Aguzzoli Heberle, Justin B. Miller, Cody J. Steely, Mark T. W. Ebbert

Sanders-Brown Center on Aging Faculty Publications

Comprehensive genomic analysis is essential for advancing our understanding of human genetics and disease. However, short-read sequencing technologies are inherently limited in their ability to resolve highly repetitive, structurally complex, and low-mappability genomic regions, previously coined as “dark” regions. Long-read sequencing technologies, such as PacBio and Oxford Nanopore Technologies (ONT), offer improved resolution of these regions, yet they are not perfect. With the advent of the new Telomere-to-Telomere (T2T) CHM13 reference genome, exploring its effect on dark regions is prudent. In this study, we systematically analyze dark regions across four human genome references—HG19, HG38 (with and without alternate contigs), and …


Data-Driven Thresholds For Standardized Classification Of Severe Alzheimer’S Disease Neuropathology Using Digital Neuropathology, Ryan K. Shahidehpour, Allison M. Neltner, Mitchell A. Klusty, Cole Corbett, Angelique D. Gonzalez, David A. Gutman, David W. Fardo, Adam D. Bachstetter, Cody Bumgardner, Margaret E. Flanagan, Peter T. Nelson Jan 2026

Data-Driven Thresholds For Standardized Classification Of Severe Alzheimer’S Disease Neuropathology Using Digital Neuropathology, Ryan K. Shahidehpour, Allison M. Neltner, Mitchell A. Klusty, Cole Corbett, Angelique D. Gonzalez, David A. Gutman, David W. Fardo, Adam D. Bachstetter, Cody Bumgardner, Margaret E. Flanagan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease neuropathological changes (ADNC)—operationalized with semi-quantitative parameters—represent the consensus-based gold standard for diagnostic evaluation of disease severity. Although useful, ADNC diagnostic frameworks have limitations, particularly in advanced disease stages where pathological severity varies widely within a given diagnostic category. Further, some individuals lacking cognitive impairment are inappropriately categorized as having severe ADNC. In this study, quantitative pathology metrics and alternative tissue sampling schemes were integrated with data about premortem cognitive status, in order to derive clinically informed neuropathologic diagnostic thresholds. Specific goals of the current study were to generate data-driven, standardized diagnostic cut-points, with the most severe stages of …


Clonal Expansion Of Cytotoxic Cd8⁺ T Cells In Lecanemab-Associated Aria, Lance A. Johnson, Kai Saito, Akhil V. Pallerla, Jessica L. Funnell, Ashley R. Ezzo, Chelsea M. Song, Douglas A. Harrison, Noah J. Norton, Lauren C. Moore, Linda J. Van Eldik, David W. Fardo, Greg E. Cooper, Josh M. Morganti Jan 2026

Clonal Expansion Of Cytotoxic Cd8⁺ T Cells In Lecanemab-Associated Aria, Lance A. Johnson, Kai Saito, Akhil V. Pallerla, Jessica L. Funnell, Ashley R. Ezzo, Chelsea M. Song, Douglas A. Harrison, Noah J. Norton, Lauren C. Moore, Linda J. Van Eldik, David W. Fardo, Greg E. Cooper, Josh M. Morganti

Sanders-Brown Center on Aging Faculty Publications

Amyloid-related imaging abnormalities (ARIA) are the principal safety concern limiting anti-amyloid therapies for Alzheimer’s disease, yet their biology remains unclear. Here we show, through multi-omic profiling of peripheral blood from three ARIA+ patients and matched controls, that ARIA is associated with coordinated reprogramming of CD8 + T cells. CD8+ effector memory (TEM) and terminally differentiated (TEMRA) subsets were expanded, clonally enriched, and transcriptionally primed for cytotoxicity and vascular trafficking. Transcription factor inference and metabolomics converged on glycolytic reprogramming favoring short-lived effector function. Ligand-receptor modeling revealed enhanced monocyte-to-T cell signaling through antigen presentation, adhesion, and chemokine axes, while integration with a …


Knowledge Based Automated Planning For Non-Coplanar Vmat Stereotactic Radiosurgery In Ocular Malignancies, Chase Cochran, Shane Mccarthy, William St. Clair, Damodar Pokhrel Jan 2026

Knowledge Based Automated Planning For Non-Coplanar Vmat Stereotactic Radiosurgery In Ocular Malignancies, Chase Cochran, Shane Mccarthy, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Background and Purpose: Stereotactic radiosurgery/radiotherapy (SRS/SRT) has emerged as a less invasive alternative to enucleation in the management of ocular malignancies. SRS/SRT planning is time-consuming, complex, and the plan quality depends on the experience of the treatment planner. We demonstrate the use of RapidPlan modeling in conjunction with HyperArc for the treatment of ocular diseases to improve planning efficiency, consistency, and quality.

Materials and Methods: A HyperArc-based RapidPlan (HARP) model was iteratively trained on 80 patient datasets that simulated ocular malignancies. Twenty additional patient datasets were reserved for model testing and comparison with manual plans. Each testing dataset was both …


Designing Theranostic Radiopharmaceutical Trials For Uterine Cervix Cancer, Denise Fabian, Molly E. Buffington, Brianna S. Cagle, Steve M. Keefe, Michael K. Schultz, Charles A. Kunos Jan 2026

Designing Theranostic Radiopharmaceutical Trials For Uterine Cervix Cancer, Denise Fabian, Molly E. Buffington, Brianna S. Cagle, Steve M. Keefe, Michael K. Schultz, Charles A. Kunos

Radiation Medicine Faculty Publications

Designing and interpreting early phase trials of theranostic radiopharmaceuticals remains challenging because it is difficult to isolate effective levels of activity in enriched patient populations that would be worth following up in later-phase development. This study explores the known challenges and emerging opportunities for clinical research on patients with uterine cervical cancer. We identified eight randomized combination trials for advanced-stage uterine cervix cancer that were activated between 2011 and 2022 and tabulated their results to determine whether combinations were better than individual constituents and which suitable study population is best situated for the study of a new theranostic agent. In …


Autologous Peripheral Nerve Tissue Grafts Implanted Into The Nucleus Basalis Of Meynert And Substantia Nigra At The Time Of Bilateral Deep Brain Stimulation In Parkinson Disease: A Report Of 2 Cases, Samuel R. Daly, Jorge E. Quintero, Lisa M. Koehl, Elizabeth Roslyn Wallace, Zain Guduru, Julie A. Gurwell, Tripp Hines, Jaimie Hixson, Saad Hulou, John T. Slevin, Frederick A. Schmitt, Greg A. Gerhardt, Craig G. Van Horne Jan 2026

Autologous Peripheral Nerve Tissue Grafts Implanted Into The Nucleus Basalis Of Meynert And Substantia Nigra At The Time Of Bilateral Deep Brain Stimulation In Parkinson Disease: A Report Of 2 Cases, Samuel R. Daly, Jorge E. Quintero, Lisa M. Koehl, Elizabeth Roslyn Wallace, Zain Guduru, Julie A. Gurwell, Tripp Hines, Jaimie Hixson, Saad Hulou, John T. Slevin, Frederick A. Schmitt, Greg A. Gerhardt, Craig G. Van Horne

Neurosurgery Faculty Publications

Background and Objectives: Cholinergic degeneration in the nucleus basalis of Meynert (NBM) is implicated in the cognitive impairment seen in Parkinson disease (PD) and is being examined as a potential therapeutic target. We have previously shown the safety of delivering investigational autologous cell-based therapy, ie, peripheral nerve tissue (PNT), to the substantia nigra (SN) at the time of deep brain stimulation (DBS) surgery in PD (DBS-Plus). In this study, we assessed the safety and feasibility of simultaneously delivering that PNT to both the NBM and SN at the time of DBS.

Methods: Two patients with idiopathic PD and mild cognitive …


A Unified Finite Element Framework For Cardiac Growth And Remodeling In Mitral Regurgitation Incorporating Fiber Reorientation And Baroreflex, Mohammad Mehri, Jonathan F. Wenk Jan 2026

A Unified Finite Element Framework For Cardiac Growth And Remodeling In Mitral Regurgitation Incorporating Fiber Reorientation And Baroreflex, Mohammad Mehri, Jonathan F. Wenk

Mechanical Engineering Faculty Publications

Mitral regurgitation (MR) triggers complex cardiac remodeling responses that alter the structure and function of the left ventricle (LV). While several models have been developed to predict myocardial growth in MR, they often neglect key concurrent adaptive mechanisms that influence both the pattern and severity of LV dilation. This study presents a unified finite element framework to systematically evaluate the individual and combined contributions of fiber reorientation (FR) and baroreflex regulation to LV growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of MR. A healthy baseline model and multiple …


Safety And Efficacy Findings From A Phase Ib/Ii Study Of Asp-1929 Photoimmunotherapy With Pembrolizumab In Recurrent And/Or Metastatic Head And Neck Squamous Cell Carcinoma, David M. Cognetti, Joseph M. Curry, Jennifer Johnson, Michael Kwon, Shirley Y. Su, Francisco Civantos, Coral Olazagasti, Joseph Valentino, Susanne Arnold, R. Bryan Bell, Michael K. Gibson, Kyle Mannion, Kathryn M. Van Abel, Katharine A. Price, Haiying Dong, Amy H. Thorne, Toshiaki Suzuki, Ann M. Gillenwater Jan 2026

Safety And Efficacy Findings From A Phase Ib/Ii Study Of Asp-1929 Photoimmunotherapy With Pembrolizumab In Recurrent And/Or Metastatic Head And Neck Squamous Cell Carcinoma, David M. Cognetti, Joseph M. Curry, Jennifer Johnson, Michael Kwon, Shirley Y. Su, Francisco Civantos, Coral Olazagasti, Joseph Valentino, Susanne Arnold, R. Bryan Bell, Michael K. Gibson, Kyle Mannion, Kathryn M. Van Abel, Katharine A. Price, Haiying Dong, Amy H. Thorne, Toshiaki Suzuki, Ann M. Gillenwater

Otolaryngology--Head & Neck Surgery Faculty Publications

Background: ASP-1929 photoimmunotherapy—cetuximab conjugated to IRDye 700DX and red light (690 nm) for localized drug activation—results in rapid, selective cell killing.

Methods: This phase Ib/II open-label study evaluated ASP-1929 photoimmunotherapy plus pembrolizumab in patients with recurrent/metastatic HNSCC (≥ 1 accessible lesion, PD-L1 combined positive score ≥ 1, ineligible for standard locoregional ther- apy). Primary objectives were safety/tolerability and objective response rate (ORR). Secondary objectives included overall sur- vival (OS) and progression-free survival (PFS).

Results: Eighteen patients (median age 63 years, 74% male) comprised the photoimmunotherapy-evaluable population. The confirmed ORR was 27.8% (95% CI 9.7–53.5); four of five responders had complete …


Assessment Of Hearing Health Among Adults In Rural Health Clinics, Mit A. Patel, David Adkins, Laura Bellnier, Anthony Mahairas, Matthew L. Bush Jan 2026

Assessment Of Hearing Health Among Adults In Rural Health Clinics, Mit A. Patel, David Adkins, Laura Bellnier, Anthony Mahairas, Matthew L. Bush

Otolaryngology--Head & Neck Surgery Faculty Publications

Objective: Hearing loss (HL) negatively impacts all aspects of health, yet poor access to hearing healthcare (HHC) among adults is a pervasive public health problem. The inaccessibility of HHC is amplified in rural adults. Rural health clinics (RHC) are a critical healthcare system tasked with improving health in rural communities and the objective of this study is to assess the prevalence of HL and the utilization of HHC within RHCs.

Methods: Using cross-sectional study design, adults were recruited from 10 RHC throughout rural Kentucky, mostly within Appalachia. The primary outcomes were (1) presence of HL on screening and (2) history …


Durable Left-Ventricular Assist Device Inflow Thrombosis Following External Outflow Graft Obstruction, Mohammad J. Malik, Jin Woo Chung, Matthias Loebe, John C. Gurley, Emma J. Birks, Dhruv Kothari, Masashi Kawabori Jan 2026

Durable Left-Ventricular Assist Device Inflow Thrombosis Following External Outflow Graft Obstruction, Mohammad J. Malik, Jin Woo Chung, Matthias Loebe, John C. Gurley, Emma J. Birks, Dhruv Kothari, Masashi Kawabori

Surgery Faculty Publications

Background: External outflow graft obstruction (EOGO) is an emerging complication due to improved pump durability. We experienced a rare sequence of complications, inflow thrombus formation following EOGO with reduced left-ventricular assist device flow.

Case Summary: A 41-year-old man, 2 years post HeartMate 3 (HM3) implantation, presented with low-flow from EOGO. Outflow graft stenting resulted in improvement but returned 1 month later with persistent low flow. Pump thrombosis was excluded. Flow had minimal response to RPM increase. Outflow graft was widely patent. Inflow obstruction was suspected, and HM3-to-HM3 exchange revealed extensive thrombus formation within the inflow cannula. Left-ventricular assist device flow …


Liposome-Encapsulated Clodronate And Cox-2 Inhibitor Treatment Impair Ventilatory Recovery But Improve Compensatory Locomotor Function Following Cervical Spinal Cord Injury In Rats, Aaron L. Silverstein, Chris M. Calulot, Christopher J. Mclouth, John C. Gensel, Warren J. Alilain Jan 2026

Liposome-Encapsulated Clodronate And Cox-2 Inhibitor Treatment Impair Ventilatory Recovery But Improve Compensatory Locomotor Function Following Cervical Spinal Cord Injury In Rats, Aaron L. Silverstein, Chris M. Calulot, Christopher J. Mclouth, John C. Gensel, Warren J. Alilain

Spinal Cord and Brain Injury Research Center Faculty Publications

Over half of all spinal cord injuries (SCIs) in the United States occur at the cervical level and can cause locomotor deficits and life-threatening breathing dysfunction. Interestingly, the bisphosphonate drug clodronate has shown efficacy in ameliorating tissue damage and improving locomotor recovery acutely after experimentally induced thoracic SCI. Thus, we hypothesized that clodronate treatment would improve recovery of breathing and locomotor function following a C2 hemisection (C2Hx) model of cervical SCI in rats. Serendipitously, changes to animal use guidelines led to the inclusion of carprofen, a non-steroidal anti-inflammatory drug (NSAID), as another independent variable in our study. We treated adult …


Traumatic Brain Injury Exacerbates Mitochondrial Dysfunction In App/Ps1 Knock-In Mice Through Time-Dependent Pathways, Elika Z. Moallem, Hemendra J. Vekaria, Teresa Macheda, Margaret R. Hawkins, Kelly N. Roberts, Samir P. Patel, Patrick G. Sullivan, Adam D. Bachstetter Jan 2026

Traumatic Brain Injury Exacerbates Mitochondrial Dysfunction In App/Ps1 Knock-In Mice Through Time-Dependent Pathways, Elika Z. Moallem, Hemendra J. Vekaria, Teresa Macheda, Margaret R. Hawkins, Kelly N. Roberts, Samir P. Patel, Patrick G. Sullivan, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cerebral hypometabolism occurs in both traumatic brain injury (TBI) and Alzheimer's disease (AD), but whether these conditions act through distinct or overlapping mechanisms is unclear. TBI disrupts cerebral metabolism via blood–brain barrier damage, altered glucose transporter expression, calcium buffering abnormalities, and oxidative damage to metabolic enzymes. AD-related hypometabolism is linked to amyloid-β (Aβ) effects on mitochondria, including impaired respiration, oxidative stress, and altered mitophagy, fusion, and fission. We tested whether TBI-induced mitochondrial dysfunction exacerbates Aβ-mediated impairment using a closed-head injury (CHI) model in APP/PS1 knock-in (KI) mice. Injuries were delivered at 4–5 months of age, before plaque formation and mitochondrial …


Current Concepts In Hip And Core Assessment To Reduce The Risk Of Acl Injury, Jeremy M. Burnham, Anthony T. Drazick, Ghislain Aminake, Darren L. Johnson, Mary Lloyd Ireland, Brian W. Noehren Jan 2026

Current Concepts In Hip And Core Assessment To Reduce The Risk Of Acl Injury, Jeremy M. Burnham, Anthony T. Drazick, Ghislain Aminake, Darren L. Johnson, Mary Lloyd Ireland, Brian W. Noehren

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: Hip and trunk (“core”) muscle dysfunction has emerged as a modifiable contributor to lower-limb biomechanics linked with non-contact anterior cruciate ligament (ACL) injuries. Clinicians increasingly target core stability and control during injury-prevention screening and post-operative rehabilitation programs; however, the literature lacks a focused synthesis of core-directed strategies for ACL injury mitigation. The purpose of this current concepts review is to synthesize current evidence on hip- and core-focused assessment and rehabilitation strategies that may mitigate ACL injury risk.

Design: Current Concepts Review.

Methods: A narrative search of PubMed and Google Scholar (January 2000 – April 2025) identified biomechanical, prospective, interventional, …


Candidate Interaction Partners Of Calpain-5 Suggest Clues To Its Involvement In Neovascular Inflammatory Vitreoretinopathy, Jozsef Gal, Vimala Bondada, Rachel Crasta, Dorothy E. Croall, Calvin P. Vary, James W. Geddes Jan 2026

Candidate Interaction Partners Of Calpain-5 Suggest Clues To Its Involvement In Neovascular Inflammatory Vitreoretinopathy, Jozsef Gal, Vimala Bondada, Rachel Crasta, Dorothy E. Croall, Calvin P. Vary, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

Although calpain-5/CAPN5 is widely expressed in mammals, little is known regarding its functions. Pathogenic mutations of CAPN5 are causal for a devastating autoimmune eye disease, neovascular inflammatory vitreoretinopathy (NIV). To provide insight into both the physiological and pathological roles of CAPN5, it is essential to identify candidate interaction partners and possible substrates. Human SH-SY5Y neuroblastoma cells, transfected with full-length catalytically dead (Cys81Ala) CAPN5-3×FLAG, were used for anti-FLAG co-immunoprecipitation (co-IP) and quantitative proteomics using Sequential Window Acquisition of all THeoretical mass spectra (SWATH-MS). Fifty-one proteins were enriched at least four-fold, p < 0.01, relative to cells transfected with an empty FLAG vector. A high proportion (24/51) of candidate CAPN5 interaction partners are associated with protein quality control, including components of the chaperonin, chaperone, and ubiquitin–proteasome systems. Additional candidate interactors include tubulins, kinases, phosphatases, G proteins, and mitochondrial proteins. CAPN5 interactions for 14 of the candidate proteins were confirmed by co-IP and immunoblotting. Of these 14 proteins, 11 exhibited in vitro calcium-induced proteolysis following co-IP with WT CAPN5-3×FLAG. Impaired calcium-induced proteolysis of co-IP proteins was observed for the pathogenic CAPN5 variants R243L and R289W. Further studies are needed to validate the association of candidate CAPN5 interactors with proteins and complexes suggested by the SWATH-MS and co-IP results, and the possible role of CAPN5 within such complexes. The possible involvement of CAPN5 in protein quality control is relevant to NIV, as defects in protein quality control have been implicated in inherited retinal disorders. Proteomic data are available via ProteomeXchange with identifier PXD068008.


Difficult-To-Treat Rheumatoid Arthritis With Concomitant Yao Syndrome With Response To Dual-Inhibitor Therapy, Nawar Aljundi, Paramarajan Piranavan Jan 2026

Difficult-To-Treat Rheumatoid Arthritis With Concomitant Yao Syndrome With Response To Dual-Inhibitor Therapy, Nawar Aljundi, Paramarajan Piranavan

Internal Medicine Faculty Publications

No abstract provided.


An Unbiased Molecular Characterization Of Peripartum Cardiomyopathy Hearts Identifies Mast Cell Chymase As A New Diagnostic Candidate, J. F. Mulvey, C. Sailer, J. S. Achter, Gregory Nathaniel Milburn, R. C. Bretherton, K. Kahnert, S. Erbil Bilir, H. Hvid, C. Pyke, F. Gustafsson, L. Adamo, Kenneth S. Campbell, K. M. Herum, A. Lundby Jan 2026

An Unbiased Molecular Characterization Of Peripartum Cardiomyopathy Hearts Identifies Mast Cell Chymase As A New Diagnostic Candidate, J. F. Mulvey, C. Sailer, J. S. Achter, Gregory Nathaniel Milburn, R. C. Bretherton, K. Kahnert, S. Erbil Bilir, H. Hvid, C. Pyke, F. Gustafsson, L. Adamo, Kenneth S. Campbell, K. M. Herum, A. Lundby

Internal Medicine Faculty Publications

Peripartum cardiomyopathy (PPCM) is a rare form of acute heart failure that develops in women toward the end of pregnancy or early postpartum. No effective, specific treatment for PPCM is available and heart transplantation or mechanical circulatory support may be required in severe cases where drug treatment for heart failure is insufficient. The mechanisms through which the disease progresses are not well understood, and despite similar clinical characteristics to dilated cardiomyopathy of other etiologies (nonperipartum cardiomyopathy; NPCM) it is not known how the molecular remodeling differs between these groups. We aimed to provide insight into the human PPCM heart using …


The Receipt Of Psychological Services And Acceptability Of Local Follow- Up Care For Childhood Cancer Survivors: Are There Rural Vs. Urban Differences?, Tyrone F. Borders, Abigayle Feather, Jerod L. Stapleton, John A. D’Orazio, Eric B. Durbin Jan 2026

The Receipt Of Psychological Services And Acceptability Of Local Follow- Up Care For Childhood Cancer Survivors: Are There Rural Vs. Urban Differences?, Tyrone F. Borders, Abigayle Feather, Jerod L. Stapleton, John A. D’Orazio, Eric B. Durbin

Psychology Faculty Publications

Purpose This study examined rural and urban parents’ reports of their children’s receipt of general follow-up care and psychological services, ratings of the acceptability of common sources of follow-up care, and ratings of local/nearby follow-up care access and effectiveness.

Methods A cross-sectional, quantitative survey was conducted among 238 (139 urban, 46 rural adjacent, and 53 rural non-adjacent) parents of childhood cancer survivors (ages 2–17 and at least 2 years since cancer diagnosis) recruited through the Kentucky Cancer Registry. Bivariate analyses and multivariable logistic regressions adjusting for predisposing, enabling, and need factors tested for differences across residence in urban counties, rural …


Comparative Evaluation Of R134a And Hfo‐1234ze Cryogen Spray Cooling Using A Mouse Model With Controllable Epidermal Pigmentation, Wangcun Jia, Yurie Jeong, Crystal Huynh, Oswald Lai, Emily Nguyen, Grant Swajian, Jade Niu, Ayana Kashikar, Joshua Khaw, Hong Pu, Bernard Choi, John August D'Orazio, J. Stuart Nelson, Bahman Anvari Jan 2026

Comparative Evaluation Of R134a And Hfo‐1234ze Cryogen Spray Cooling Using A Mouse Model With Controllable Epidermal Pigmentation, Wangcun Jia, Yurie Jeong, Crystal Huynh, Oswald Lai, Emily Nguyen, Grant Swajian, Jade Niu, Ayana Kashikar, Joshua Khaw, Hong Pu, Bernard Choi, John August D'Orazio, J. Stuart Nelson, Bahman Anvari

Pediatrics Faculty Publications

Objectives: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance.

Methods: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1re/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold …


In Vivo Telemetry To Record Long-Term Cardiovascular Parameters, Temperature, And Activity In Spinal Cord Injury Rat Models, Sajeev Kaur, Anna M. Baur, Jillian A. Condrey, Dorottya P. Gal, Samir P. Patel, John C. Gensel Jan 2026

In Vivo Telemetry To Record Long-Term Cardiovascular Parameters, Temperature, And Activity In Spinal Cord Injury Rat Models, Sajeev Kaur, Anna M. Baur, Jillian A. Condrey, Dorottya P. Gal, Samir P. Patel, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Higher-level spinal cord injury (SCI) above thoracic level 6 (T6) disrupts autonomic function and contributes to secondary complications, including fluctuations in blood pressure, heart rate, and temperature. In rats, the placement of telemetric implants in the descending aorta offers a robust methodology for assessing various cardiovascular parameters, such as systolic and diastolic pressure, mean arterial pressure, and heart rate. Core body temperature and animal activity can also be recorded following telemetric implant placement. A rat with a telemetric implant is kept on the receiver plate connected to a computer system for recording various parameters. Continuous long-term recordings at defined time …


Leveraging The Clinical Potential Of Spatially Fractionated Radiotherapy For Enhanced Therapeutic Impact & Rapid Management Of Large And Unresectable Tumors, Joshua Misa Jan 2026

Leveraging The Clinical Potential Of Spatially Fractionated Radiotherapy For Enhanced Therapeutic Impact & Rapid Management Of Large And Unresectable Tumors, Joshua Misa

Theses and Dissertations--Radiation Medicine

Annually, about two million people are diagnosed with cancer in the United States alone, with nearly half receiving radiation therapy during their course of treatment. Advances in radiation therapy focuses on widening the therapeutic window by maximizing the tumor local control while minimizing normal tissue toxicities. Since the 1950s, spatially fractionated radiotherapy (SFRT) has been a niche treatment technique for treating large, unresectable tumors while sparing the skin tissue. Unlike conventional radiation therapy, which delivers a uniform dose to the tumor, SFRT utilizes an alternating pattern of high- and low-dose irradiation regions. However, significant challenges and knowledge gaps remain, most …


Establishing An Advanced Practice Provider-Led Transient Ischemic Attack Clinic: A Quality Improvement Initiative, Brittany A. Young Jan 2026

Establishing An Advanced Practice Provider-Led Transient Ischemic Attack Clinic: A Quality Improvement Initiative, Brittany A. Young

DNP Projects

Background: Due to lack of subspecialized neurological care in many rural community settings, care in tertiary hospitals is in demand. Insufficient care pathways can lead to lack of bed and provider availability. Advanced Practice Provider Transient Ischemic Attack clinics have been shown to be safe alternatives to hospital admission, for patients who meet criteria. This study targeted practice change at a 1000 bed tertiary academic hospital.

Methods: The quasi-experimental study sample inclusion criteria included Transient Ischemic Attack patients presenting to the emergency department with an ABCD2 < 4, complete symptom resolution, and no new cardiac changes on monitoring. A pre and post survey with educational PowerPoint intervention was provided to all emergency department and Neurology providers and nurses. A Transient Ischemic Attack clinic was established with a corresponding order set to be utilized for streamlined outpatient work up.

Results: During the pilot period, 29 admissions were deferred with 69% …


Wastewater Surveillance For Sars-Cov-2 In Rural Kentucky, 2021–2023, James W. Keck, Reuben Adatorwovor, Ann Noble, Savannah Tucker, William Strike, Soroosh Torabi, Mohammad Dehghan Banadaki, Blazan Mijatovic, Steven K. Roggenkamp, Donna Mcneil, Lindell Ormsbee, Scott M. Berry Jan 2026

Wastewater Surveillance For Sars-Cov-2 In Rural Kentucky, 2021–2023, James W. Keck, Reuben Adatorwovor, Ann Noble, Savannah Tucker, William Strike, Soroosh Torabi, Mohammad Dehghan Banadaki, Blazan Mijatovic, Steven K. Roggenkamp, Donna Mcneil, Lindell Ormsbee, Scott M. Berry

Family and Community Medicine Faculty Publications

Wastewater testing for SARS-CoV-2 provided useful public health information during the COVID-19 pandemic yet was underutilized in rural communities. We addressed this gap by implementing wastewater surveillance and assessing its performance in 10 communities in Eastern Kentucky. We collected wastewater samples 1–2 times weekly at 10 wastewater treatment plants (WWTPs) from May 2021 until April 2023 and measured SARS-CoV-2 RNA concentrations using polymerase chain reaction testing. We calculated time-lagged correlations between wastewater concentrations and county-level reported COVID-19 cases by site. We developed a generalized linear model to estimate COVID-19 incidence from wastewater SARS-CoV-2 concentrations. The 10 participating WWTPs served 2430 …


Perceptions Of The Proposed Food And Drug Administration Graphic Cigarette Warnings Among Adults Who Smoke On A Nondaily Or Daily Basis: A Within-Subjects Experiment, Bethany Shorey Fennell, Renee E. Magnan, Jennifer I. Vidrine, Damon J. Vidrine Jan 2026

Perceptions Of The Proposed Food And Drug Administration Graphic Cigarette Warnings Among Adults Who Smoke On A Nondaily Or Daily Basis: A Within-Subjects Experiment, Bethany Shorey Fennell, Renee E. Magnan, Jennifer I. Vidrine, Damon J. Vidrine

Family and Community Medicine Faculty Publications

Introduction: People who smoke nondaily represent nearly one third of U.S. adults who smoke and experience significant smoking-related morbidity and mortality, yet they are rarely considered when evaluating the efficacy of graphic cigarette warnings.

Method: In October 2019, U.S. adults who smoked nondaily ( n =59) and daily ( n =183) evaluated 13 Food and Drug Administration–proposed graphic warnings and 13 equivalent text-only warnings on the extent to which they elicited understanding, perceived new knowledge, worry about smoking, and discouragement to smoke and were believable. Repeated-measures ANOVA and planned comparisons tested for between-subjects (smoking status) and within-subjects (warning type) effects. …