Digital Commons Network^™

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 …

Zero Tolerance Or Strong Cultural Diversity: The Hard Case Of Female Genital Surgery, James M. Donovan, Christiane Canant

Law Faculty Scholarly Articles

This article applies a thesis favoring strong cultural diversity to defend a subject-centered policy regarding female genital surgeries (FGS). That idea posits that cultural variation holds an intrinsic value that should be presumptively respected when setting policy and creating law. Correlatively, cultural homogenization, especially by force, should be resisted. 

Taking as a starting point the recent celebration of the United Nation’s Day of Zero-Tolerance for Female Genital Mutilation, the paper reviews the context of FGS practices in various societies and critiques the inconsistencies of U.N. arguments to advance its goal of total elimination by 2030. Especially problematic for the U.N. …

Characteristics Of Pulmonary Vs. Extrapulmonary Tuberculosis Cases In Kentucky From 2020 To 2024, Mariam M. Alkhairat

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objective: Tuberculosis (TB) remains an important public health concern in the United States, especially among people experiencing social and clinical vulnerabilities. Extrapulmonary TB, which occurs outside of the lungs, can be harder to detect and diagnose than pulmonary TB. This study aimed to describe the demographic and clinical characteristics of people with active TB in Kentucky and to identify factors associated with extrapulmonary TB.

Methods: Secondary surveillance data were obtained from the Kentucky Department for Public Health (KDPH) using the National Tuberculosis Surveillance System (NTSS). The study sample included 301 confirmed active TB cases reported in Kentucky. Descriptive statistics were …

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 …

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …

Unveiling The Shadows: An Exploratory Study On Ghostwriting, Gray Markets, And The Ethics Of Contract Cheating, Micah Crawford

Theses and Dissertations--Educational Policy Studies and Evaluation

Contract cheating has become an increasingly complex challenge for higher education, particularly as digital platforms, global academic labor markets, and generative artificial intelligence reshape the production and detection of academic work. While much of the existing literature examines contract cheating from the perspectives of students, faculty, and institutions, less attention has been given to the individuals who produce ghostwritten academic work. This dissertation addresses that gap by exploring how shadow scholars understand their roles, ethical boundaries, and participation within the academic integrity ecosystem.

Using an exploratory qualitative design, this study draws on twelve semi-structured narrative interviews with six freelance academic …

Are Multiple-Choice And Open-Ended Assessments Consistent In Predicting Science Achievement? Multivariate Multilevel Evidence From Chinese Students And Schools, Quan Wu

Theses and Dissertations--Education Sciences

A multivariate multilevel model was developed and applied to secondary data from a large-scale science assessment of Grade 8 students in China to examine the consistency between multiple-choice and open-ended formats of assessment in predicting science achievement at the student and school levels. The sample included 44,534 students from 159 schools across two regions. Multivariate multilevel results indicated a moderately positive consistency between the two formats at the student level and a strongly positive consistency at the school level; these consistencies were stable across regions and did not depend on student and school characteristics. The findings have important practical implications …

Role Of Estrogen Receptor Alpha In Modulating The Circadian System In Female Mice, Victoria Alvord

Theses and Dissertations--Biology

Circadian rhythms are approximately 24-hour cycles of physiology and behavior. Circadian rhythms of eating, or meal timing, are linked to cardiometabolic dysfunction in humans. Mistimed eating, such as breakfast skipping and eating late at night, increases the risk of obesity, diabetes, and cardiovascular disease in humans. Likewise, disrupted eating rhythms cause obesity in mice. This dissertation investigates how estrogens regulate eating behavior rhythms and tissue clock timing in female mice. Chapter 1 reviews three key components critical to this work. The first is an overview of the field of chronobiology and the function of the circadian system. The second is …

Visual Genealogies Of Disability In Mexican Visual Culture, Daniela Calvache Garcia

Theses and Dissertations--Hispanic Studies

Disability in Mexico is a visually constructed category, shaped by a long genealogy of representation in which images of bodily difference actively participate in defining power and the management of all bodies. The discursive forces that define disability as unproductivity reduce body-minds to the service of the economic system, affecting our relationship with death, illness, reproduction, size, youth, and beauty. Across the Mesoamerican visual space, such representations have long unsettled dominant systems of truth about bodies. This dissertation examines how conceptions of disability are produced, negotiated, and reimagined through three historical moments and cultural expressions: Pre-Hispanic Mayan imagery, Mexican colonial …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Environmental Predictors Of Human Lyme Disease Incidence Across Appalachian Counties In Kentucky, Virginia, And West Virginia, 2000-2019, Karlie D. Rennison

Theses and Dissertations--Epidemiology and Biostatistics

This ecological study examined county-level environmental, landscape, and host-related predictors of Lyme disease incidence across Kentucky, Virginia, and West Virginia from 2000-2019. Lyme disease is an emerging public health concern in the Appalachian region, where geographic expansion and shifting ecological conditions may influence disease risk.

Lyme disease case rates (per 10,000 population) were analyzed in relation to climate variables, land cover metrics, host density measures, and rurality using publicly available data sources. Descriptive and regression analyses were conducted to evaluate associations between candidate predictors and disease incidence.

Substantial geographic variation in Lyme disease incidence was observed, with higher case rates …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Exploring The Limitations Of Substrate Scope In Dimethylallyltryptophan Synthases, Evan T. Miller

Theses and Dissertations--Pharmacy

Natural products (NPs), are the largest source of bioactive compounds in Nature, and are essential to the treatment of human disease. Nearly 50% of drugs approved for use from 1981 to 2019 owe some aspect of their development to NPs, either in terms of their structure, pharmacophore, or mechanism of action. However, NPs are difficult to structurally optimize. Chemoenzymatic methods for NP derivatization have been increasingly seen as practical alternatives to traditional synthetic methods. Prenyltransferases (PTs) are involved in the primary and secondary metabolism of plants, bacteria, and fungi, and they are key enzymes in the biosynthesis of many clinically …

Investigating The Potential Role Of Toxoplasma Gondii In The Development Of Equine Protozoal Myeloencephalitis, Brooklyn Nicole Shirah

Theses and Dissertations--Veterinary Science

Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses prevalent in the Americas, caused by the coccidian parasites Sarcocystis neurona and Neospora hughesi. Toxoplasma gondii is a related parasite that infects nearly all warm-blooded animals, including horses. Prior studies show conflicting results on whether T. gondii contributes to EPM, in part because no validated T. gondii serologic assay exists in horses. This study developed a recombinant TgSAG1 ELISA and confirmatory Western blot. These assays evaluated T. gondii seropositivity in 789 serum samples from healthy and neurologic horses across multiple geographic regions and examined 31 paired serum:CSF samples for …

Molecular Mechanisms And Metabolic Consequences Of Glucocorticoid Resistance, Genesee J. Martinez

Theses and Dissertations--Pharmacology and Nutritional Sciences

Glucocorticoids are vital steroid hormones that govern metabolism, stress responses, and immune functions through intricate, tissue-specific mechanisms, both genomic and non-genomic. These hormones bind to the glucocorticoid receptor (GR), which then acts as a transcription factor to modulate gene expression. Chronic elevation of glucocorticoid levels may lead to glucocorticoid resistance, resulting in adiposity, inflammation, and insulin resistance, thereby adversely affecting multiple metabolic tissues. Whether produced endogenously or administered exogenously, excessive, chronic glucocorticoid concentrations impair glucocorticoid signaling. Although there are two primary isoforms of the receptor, GR⍺ and GRβ, only GR⍺ interacts with glucocorticoids.Through the research conducted in this dissertation, we …

Expanding The Role Of Muscle Stem Cell Fusion In Muscle Under Hypertrophic Stimulus, Jensen Goh Zhong Sheng

Theses and Dissertations--Physiology

Muscle stem cells (MuSCs) are a unique stem cell population that can activate in response to both injury and growth stimuli. Studies on muscle regeneration have shown MuSC activation follows a uniform progression through proliferation, differentiation, and fusion. Therefore, to determine whether MuSC replication is a prerequisite for differentiation under hypertrophic stimulus, I used a lineage-tracking mouse model (Pax7^rtTA; TRE-H2B-GFP) to label MuSC nuclei and simultaneously tracked DNA synthesis via EdU incorporation. This dual-labeling approach allowed us to not only distinguish MuSC-derived nuclei but also demarcate which MuSC had proliferated prior to fusion. I then employed a mechanical …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Investigation Into The A/Ss Of Cervical Cancer And Its Effects On Tumor Control Probability In Radiation Therapy, Cameron Thayer-Freeman

Theses and Dissertations--Radiation Medicine

The standard of care for locally advanced cervical cancer is chemoradiation, consisting of conventional external beam therapy (EBT) followed by a boost of high dose rate (HDR) brachytherapy. These two radiation treatments will illicit different degrees of biological response depending on the tissue in question, and quantifying the overall effect the combined treatments will have require some form of biological modeling. The linear quadratic (LQ) model of cell survival is the most widely used radiobiological model in clinics across the nation.

It is quantified by the parameters a and ß, which model how radiation generates lethal damage in a population …

Seasonal Population Dynamics And Interspecific Interactions Of Drosophila Suzukii, Eleanor Mccabe

Theses and Dissertations--Entomology

Invasive species are a growing problem, and it is important to investigate how invasives interact with novel ecosystems, which are characterized by distinct abiotic and biotic factors. In this dissertation, I investigate abiotic and biotic factors affecting two invasive pests in central Kentucky, Drosophila suzukii and Zaprionus indianus. In Kentucky, seasonality, and landscape features on population dynamics and fitness are unknown. I found that D. suzukii overwinters in Kentucky and that wild berry species improve winter survival. I used local weather data to identify meteorological variables that best predict D. suzukii populations. I tested the extent to which D. suzukii …

Fusarium Head Blight Of Hemp: A Destructive Disease Emerges On A New Host, Henry Smith

Theses and Dissertations--Plant Pathology

Hemp was reintroduced as a commercial crop in 2018 after a near 50-year production ban under the Controlled Substances Act. Since reintroduction, Kentucky has consistently ranked among the top five hemp producing states in the US. Surveys have shown that hemp is susceptible to a multitude of diseases that impact production. Among the most concerning diseases in Kentucky is Fusarium head blight (FHB). FHB is a major disease of cereals that is caused by various Fusarium species, predominately F. graminearum. FHB of hemp caused by F. graminearum was first reported in Kentucky in 2020. A survey of 25 different …

Managing Dietary Nonstructural Carbohydrates In Insulin Dysregulated Horses: Pasture, Long-Stem Forage, And Restrictive Grazing Strategies, Morgan J. Askins

Theses and Dissertations--Veterinary Science

Insulin dysregulation (ID) is a complex endocrine disorder, impacting a large percentage of the equine population. ID is the defining characteristic of equine metabolic syndrome (EMS). Within the various classifications of EMS horses, the commonality is ID and their higher risk of laminitis. To mitigate insulin response and laminitis risk in ID horses, current management focuses on restricting pasture exposure and feeding low nonstructural carbohydrate (NSC) rations. Minimal studies have evaluated how ID horses respond to pasture of various NSC, long-stem forages, and restrictive grazing strategies. Providing horse owners and managers with improved nutritional management recommendations for ID horses with …

Equid Major Histocompatibility Complex (Mhc) Evolution & Genome Organization, Lauren C. Johnson

Theses and Dissertations--Veterinary Science

The evolution of modern horses has a well-documented fossil record and has long been of interest to the genetics community. Although non-caballine equids (e.g. zebras, donkeys, and asses) can hybridize with horses, the resulting offspring are typically infertile. Despite these reproductive barriers, genomic analyses reveal regions of high sequence similarity among equid species. This dissertation investigates the role of historical introgression in the evolution of modern Equus species. The first chapter re-evaluates earlier findings derived from a limited horse population and a single reference genome. The variants of the identified regions were pushed through Ensembl’s Variant Effect Predictor to assess …

Environmental Detection And Quantification Of Equid Alphaherpesviruses In Equine Facilities Using Air Sampling, Emma E. Hyde

Theses and Dissertations--Veterinary Science

Equid alphaherpesvirus 1 and 4 (EHV-1/-4) circulate at equestrian facilities, contributing to outbreaks. Due to the complexities of the pathogen, including the limited predictability of reactivation from latency and the effects associated with secondary sites of viral replication, abortion, and neurologic disease, EHV infections are of utmost concern to the equine industry. Recent studies have highlighted the prevalence of the viruses in stabling areas at competitions, though little is known about this phenomenon in other high-traffic equine environments. This thesis presents two studies using air sampling surveillance methods to further explore the viral detection in other equine environments (veterinary facility …

Using Camera-Based Unmarked Spatial Capture-Recapture Modeling To Estimate Reintroduced Elk (Cervus Canadensis) Population Parameters And Distribution In Southeastern Kentucky, Claire Marie Muia

Theses and Dissertations--Forestry and Natural Resources

Estimation of population parameters is important for wildlife management decisions. Elk reintroduced to southeastern Kentucky experienced early irruptive population growth and are currently monitored using a statewide harvest-based statistical population reconstruction model (SPR) across the Kentucky Elk Restoration Zone (KERZ). Because the SPR model is spatially coarse and difficult to scale to the smaller management units comprising the KERZ, we conducted a spatially explicit capture-recapture study using a clustered camera-trapping array deployed for 10 weeks from June–August 2024 to estimate elk population parameters within Management Unit 4. Due to a lack of resights of GPS-marked elk, population parameters were estimated …

From Floodplain To Floodplain: Analyzing Stream And Riparian Restoration Methodologies And Impacts, Noah P. Lane

Theses and Dissertations--Biosystems and Agricultural Engineering

Stream restoration is a relatively new scientific field. Currently, there is not a definitive methodology for performing restorations that all professionals in industry and academia can agree upon. This has allowed for multiple ideologies to be developed and altered that vary by geographic location and the professional using them. In addition to the methodologies used, the publicly available design guidance published by state government organizations also varies by regulatory authority, method of analysis, ecoregion, and restoration objectives. In some cases, design guidance is replicated from a different geographical area and may not satisfy local needs or existing site conditions. Since …

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 …

Exploring High School Students’ Learning Interests And Information Sources On Viruses And Covid-19, Sahar Alameh, James W. Keck, Elizabeth Loh, Lin Xiang, Scott M. Berry, Anna G. Hoover, Abigail Knapp, Savannah Tucker

Science, Technology, Engineering, and Mathematics (STEM) Education Faculty Publications

This study investigates high school students’ health-information seeking behaviors related to COVID-19 and viruses in a rural area of the south-central United States, and how these behaviors relate to students’ knowledge, perceptions, and learning interests. Survey data were collected from 83 students in Spring 2023, during the post-pandemic period, as part of a STEM and public health unit. Drawing on frameworks from Health Information-Seeking Behavior and student interest, the study examines students’ COVID-19 information sources, how these sources relate to their knowledge about viruses and their perceptions of COVID-19, and the specific topics about which they were most interested in …

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

Signaling Scaffold Shoc2 Regulates Lymphangiogenesis By Suppressing Mtorc1-Mediated Ifn Responses, Patricia Wilson, Vishakha Vishwakarma, Rebecca Norcross, Kashmira Khaire, Van N. Pham, Brant M. Weinstein, Hyun Min Jung, Emilia Galperin

Molecular and Cellular Biochemistry Faculty Publications

An interplay of growth factors and signaling pathways governs the development and maintenance of lymphatic vasculature, ensuring proper fluid homeostasis and immune function. Disruption of these regulatory mechanisms can lead to congenital lymphatic disorders and contribute to various pathological conditions. However, the mechanisms underlying the molecular regulation of these processes remain elusive. Here, we reveal a critical and previously unappreciated role for the signaling scaffold protein Shoc2 in lymphangiogenesis. We demonstrate that loss of Shoc2 results in near-complete loss of lymphatic vasculature in vivo and senescence of lymphatic endothelial cells in vitro. Mechanistically, Shoc2 is required for balancing signaling through …