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Dihydropyrimidine Enzyme Activity And Its Effect On Chemotherapy Toxicity: Importance Of Genetic Testing, Alexia Shamaei Zadeh, Danielle Roberts, Abby Williams, Deepali Pandey, John L. Villano

Markey Cancer Center Faculty Publications

Purpose

Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.

Case

A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000). Capecitabine is used as a component of first-line adjuvant therapy by approximately 2 million patients worldwide each year. Capecitabine is metabolized to fluorouracil via the enzyme dihydropyrimidine dehydrogenase (DPD). With worsening pancytopenia …

Astrovascular Decoupling In Awake 5×Fad Mice Is Associated With Reduced Astrocytic Calcium, Ruei-Lung Lin, Sophiya L. Sims, Nicholas A. Wright, Léopoldine B. Galopin, Blaine Weiss, Susan D. Kraner, Jacquelyn E. Rhinehart, Ting-Hsuan Lu, Pradoldej Sompol, Christopher M. Norris, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

INTRODUCTION

Evidence points to dysregulated Ca²⁺ in neurons and astrocytes in models of amyloidosis. While most of these data were obtained in vitro or in vivo under anesthesia, less work has investigated these variables in awake ambulating mice.

METHODS

Astrocytic Ca²⁺ fluctuations (GCaMP8f) were imaged concomitantly with vasoreactivity in S1 on a two-photon microscope during rest and ambulation. Single-cell resolution variables were extracted using continuous wavelet transform and traditional ΔF/F measures.

RESULTS

Along with increases in amyloid beta (Aβ) accumulation, we found significant reductions in measures of astrocyte functional connectivity, pairwise correlations, and network synchronicity in older 5×FAD …

A Framework For Ai Implementation In Construction: Use Cases, Challenges, And Benefits For Contractors, Jaqueline De Aquino Leite Gomes

Theses and Dissertations--Civil Engineering

The construction industry is one of the most important sectors that contribute to the economy worldwide, but it has been very slow in adopting digital transformation. Artificial Intelligence is the backbone of digital innovation, and it can help solve inefficiencies, improve safety, and enhance decision-making in construction. This thesis reviews 85 academic papers, identifies 354 AI use-cases, 180 benefits, and 173 challenges. Key findings have looked at the role of AI in safety monitoring, design optimization, and operational efficiency, while barriers involve data scarcity, high costs, and readiness of the workforce.

All of these challenges have one very handy framework …

Advancing Clinical Trial Readiness In White Matter Disease And Related Dementias: Key Steps For Future Research Progress, Pradoldej Sompol, Gregory A. Jicha, Jason D. Hinman, Adam M. Brickman, Steven M. Greenberg, Konstantinos Arfanakis, Marion S. Buckwalter, Irene Lorenzo Llorente, Jeff D. Williamson, Michael S. Wolf, Eric E. Smith, Aditi Gupta, Margaret E. Flanagan, Miguel A. Vazquez, Jeffrey M. Burns, S. Thomas Carmichael, Frank C. Barone

Pharmacology and Nutritional Sciences Faculty Publications

White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer’s disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate …

Description Of Implementing A Mail-Based Overdose Education And Naloxone Distribution Program In Community Supervision Settings During Covid-19, Carrie B. Oser, Margaret Louise Mcgladrey, Douglas Oyler, Hannah K. Knudsen, Sharon L. Walsh, Susannah Stitzer, Michael Goetz, Marisa Booty, Erica Hargis, Sarah Johnson, Michele Staton, Patricia R. Freeman

Behavioral Science Faculty Publications

Introduction: This study uses the Exploration, Preparation, Implementation , and Sustainment (EPIS) model to retrospectively describe the mail-based overdose education and naloxone distribution (OEND) program developed in collaboration with the Kentucky Department of Corrections (DOC) for use in the HEALing Communities Study in Kentucky (HCS-KY) and details the reach of this innovative delivery model.

Methods: HCS-KY is a community-engaged cluster-randomized trial assessing the effects of implementing evidence-based practices, including OEND, on overdose death reduction across 16 communities highly impacted by the opioid epidemic in Kentucky. ⁶ The study launch coincided with the COVID-19 pandemic. All coalitions in the 16 HCS-KY …

Multi-Scale Computational Mechanical Modeling Of Complex Multi-Phase Materials Systems, Naji Al-Mashrafi

Theses and Dissertations--Chemical and Materials Engineering

This thesis employs finite-element–based computational methods to investigate how microstructural features and material heterogeneity govern mechanical behavior across three distinct complex systems. First, the elastic response of open-cell metallic foams is analyzed using large ensembles of model RVEs generated with the Kentucky Random Structures Toolkit (KRaSTk); finite-element homogenization reveals that effective stiffness is not dictated by relative density alone, as the skewness of ligament-length distributions—captured by the second Pearson’s coefficient—exerts a strong and previously unrecognized influence, with structures enriched in short load-bearing ligaments exhibiting consistently higher stiffness even at fixed density and connectivity. The second study examines heterogeneous polycrystalline solids …

A Knowledge-Based Planning Model To Identify Fraction-Reduction Opportunities In Brain Stereotactic Radiotherapy, Shane Mccarthy, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Objective: To develop and validate a HyperArc-based RapidPlan (HARP) model for three-fraction brain stereotactic radiotherapy (SRT) plans to then use to replan previously treated five-fraction SRT plans. Demonstrating the possibility of reducing the number of fractions while achieving acceptable organs-at-risk (OAR) doses with improved target biological effective dose (BED) to brain lesions. Methods: Thirty-nine high-quality clinical three-fraction HyperArc brain SRT plans (24–27 Gy) were used to train the HARP model, with a separate 10 plans used to validate its effectiveness. Fifty-eight five-fraction HyperArc brain SRT plans (30–40 Gy) attempted to be retrospectively replanned for three fractions scheme using the HARP …

An Investigation Into The Feasibility And Efficacy Of Stereotactic Radiosurgery For 1–3 Cm Single Brain Lesions On The Ring-Mounted Halcyon Linac, Kristin J. Hazelwood, Shane Mccarthy, Josh Misa, David Castelvetere, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose: An evaluation of the accuracy, safety, and efficiency of the Halcyon ring delivery system (RDS) for stereotactic radiosurgery (SRS) treatment to relatively small (1–3 cm) brain lesions.

Methods: After completing the extensive in-house quality assurance checks including Winston–Lutz test and independent dose verification via MD Anderson IROC SRS head phantom irradiation on Halcyon, fifteen brain SRS patients previously treated with a single dose of 20 Gy on TrueBeam (6MV-FFF) with HyperArc geometry were retrospectively replanned on Halcyon (6MV-FFF). Plan quality metrics including conformity index (CI), gradient index (GI), gradient distance (GD), PTV coverage, gross tumor volume (GTV) dose, heterogeneity …

A Predictive Quality Assurance Model For Patient-Specific Gamma Passing Rate Of Hyperarc-Based Stereotactic Radiotherapy And Radiosurgery Of Brain Metastases, Shane Mccarthy, Brent Harrison, Damodar Pokhrel

Radiation Medicine Faculty Publications

Objective: Measurement-based patient specific quality assurance (PSQA) is an increasingly debated topic among medical physicists. Developments like online adaptive radiotherapy and same-day stereotactic treatments limit the time to do measurement-based PSQA. Herein, we develop a predictive machine learning model to supplement PSQA by predicting the gamma passing rate (GPR) per stereotactic arc. This streamlines PSQA, providing planners the insight to replan potentially sub-optimal plans, to mitigate machine time inefficiencies.

Methods: 122 patients that had previously received HyperArc stereotactic radiosurgery/radiotherapy on a TrueBeam LINAC (Millenium 120 MLCs, 6MV-FFF) were used to generate a long short-term memory (LSTM) recurrent neural network to …

Automated Hippocampal Sparing Whole Brain Radiotherapy With Simultaneous Integrated Boost For Multiple Brain Metastases: Halcyon, Hyperarc On Truebeam, And Coplanar Truebeam, Shane Mccarthy, Ryan Clark, Anthony Magliari, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose: To demonstrate the ease and feasibility that hippocampal sparing whole brain (WB) simultaneous integrated boost (HSWB-SIB) plans can be generated using knowledge-based planning and Eclipse Scripting Application Programming Interface (ESAPI) for three different modalities, HyperArc on TrueBeam (TB-HA), a coplanar beam arrangement on TrueBeam (TB-Co), and the ring-mounted Halcyon LINAC (Hal).

Methods: Twelve patients with 2–14 brain metastases were retrospectively replanned for HSWB-SIB using a published HSWB RapidPlan model with modifications for the automated addition of SIB to metastases. Prescribed dose was 30 Gy to the WB planning target volume (PTV) and 50 Gy to the metastases in 10 …

Feasibility Of Treatment Planning With Hyperarc Stereotactic Radiosurgery Methods For Ocular Tumors, Chase Cochran, Shane Mccarthy, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objectives

Currently, ocular disease is primarily managed with COMS plaque brachytherapy. Various stereotactic radiosurgery (SRS) platforms have also been employed, yet widespread access remains a challenge. Herein, we demonstrate the feasibility of using the HyperArc SRS system to provide an additional platform for the treatment of ocular malignancies.

Materials/methods

Twenty previously treated COMS patients with ocular melanoma were selected for a retrospective HyperArc SRS planning study. The average gross tumor volume (GTV) derived from MRI was 1.19 ± 0.60 cc. Planning target volumes (PTV) were generated from a 2 mm expansion of the GTVs. HyperArc plans were created for a …

Establishing A Variant Allele Frequency Cutoff For Manual Curation Of Medical Exome Sequencing Data, Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B. Miller

Pathology and Laboratory Medicine Faculty Publications

Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. …

Ex Vivo Single-Molecule Analysis Of Ryanodine Receptor 2 Assembly In Cardiac And Neuronal Tissue, Qianye Yin, Christopher I. Richards

Chemistry Faculty Publications

Understanding receptor assembly is critical for elucidating the mechanisms underlying their function and regulation in physiological processes. While traditional in vitro single-molecule studies rely on isolating proteins from heterologous expression systems, they often fail to capture the in vivo physiological complexity involved in the organization and assembly of cell surface proteins. This protocol employs Total Internal Reflection Fluorescence Microscopy (TIRFM) to study GFP-tagged Ryanodine Receptor 2 (RyR2) molecules encapsulated within nanoscale vesicles. These vesicles, generated from organs rapidly extracted from the animal, effectively provide a snapshot of the receptor's assembly state at the time of extraction, enabling detailed analysis of …

Incarceration Reimagined: A Diversionary Option For Serious Felony Offenders, Jane Mitchell

Kentucky Law Journal

No abstract provided.

Converting “Nonlesional” Imaging Occult Epilepsy Into A Focal Lesional Entity Using Advanced Imaging Techniques: Illustrative Case, Muhammad Usman Khalid, Flavius D. Raslau, Valentinos Zachariou, David Powell, Zachary Winder, Ryan Cloyd, Sarah Helen Thomas, John Kuipers, Rachel Ward Mitchell, Riham H. El Khouli, Timothy J. Ainger, Sally Mathias, Farhan A. Mirza

Neurosurgery Faculty Publications

BACKGROUND To achieve the best possible outcome in surgical refractory epilepsy, the seizure onset zone must be accurately identified prior to treatment.

OBSERVATIONS A 38-year-old man presented with tonic-clonic and focal seizures 2–3 times per month, refractory to antiseizure medications. Scalp EEG, MRI, PET, ictal SPECT, magnetoencephalography, and stereo-EEG (SEEG) did not provide conclusive seizure onset zone localization. Subsequently, the patient was included in the authors’ ongoing postictal arterial spin labeling (ASL) study and additional postprocessing was performed with a morphometric analysis program (MAP) and texture analysis. Using these results, the authors reexamined the original structural MR images, with attention …

New Insights Into The Ovulatory Process In The Human Ovary, Misung Jo, Mats Brännström, James W. Akins, Thomas E. Curry

UK CARES Faculty Publications

BACKGROUND: Successful ovulation is essential for natural conception and fertility. Defects in the ovulatory process are associated with various conditions of infertility or subfertility in women. However, our understanding of the intra-ovarian biochemical mechanisms underlying this process in women has lagged compared to our understanding of animal models. This has been largely due to the limited availability of human ovarian samples that can be used to examine changes across the ovulatory period and delineate the underlying cellular/molecular mechanisms in women. Despite this challenge, steady progress has been made to improve our knowledge of the ovulatory process in women by: (i) …

Clinicians Perspective On The Implementation Of Person-Centered Care In Persons With Aphasia, Carmen S. Alderman

Theses and Dissertations--Communication Sciences and Disorders

This paper examines speech-language pathologist perspective on implementing person-centered care for persons with aphasia. Person-centered care is based on the social model, which emphasizes the importance of including the client. The survey addressed clinicians’ use of person-centered care related to collaborative goal setting and treatment planning, as well as facilitators and barriers to implementing person-centered care for individuals with aphasia based on the view of practicing clinicians across a variety of settings. The results indicated most speech-language pathologists have heard of person-centered care, understand the importance of involving clients in goal setting, ask clients about their preferences when setting goals, …

Exploiting Artificial Intelligence And Optimization For Smart Agriculture, Jackson K. Butcher

Theses and Dissertations--Computer Science

Dynamic integration of Cyber-Physical Systems (CPS) and Artificial Intelligence (AI) has become a vital component for unlocking the potential of smart agriculture. Currently, limitations such as limited computational resources, poor network connectivity, and rigid treatment strategies stifle optimal agricultural outcomes. This creates a challenge of leveraging the capabilities of modern artificial intelligence to combat the natural and artificial constraints of the smart agriculture environment. The primary contribution of this thesis is the development of frameworks to alleviate the overhead data and computational demand for AI within smart agriculture settings. The first framework, iCrop+, utilizes TinyML and LoRa to guarantee high-precision …

Biomedical Relation Extraction In The Era Of (Large) Language Models, Yuhang Jiang

Theses and Dissertations--Computer Science

Biomedical relation extraction is a key task in information extraction supporting downstream applications such as knowledge discovery, information retrieval, and question answering. As such, improvements in relation extraction (RE) are expected to have major implications for other information needs in biomedicine. In this dis- sertation, we pursue biomedical relation extraction in several advanced settings with recent advances in large language models (LLMs) and retrieval augmented generation (RAG). First, we address an important slot filling task on social media that arose during the Covid-19 pandemic, using the idea of continuous prompts with encoder models. Next, we handle a tricky dynamic n-ary …

Efficacy Of Deferoxamine Mesylate In Serum And Serum-Free Media: Adult Ventral Root Schwann Cell Survival Following Hydrogen Peroxide-Induced Cell Death, Yee Hang Ethan Ma, Abhinay R. Putta, Cyrus H. H. Chan, Stephen R. Vidman, Paula V. Monje, Giles W. Plant

Neurosurgery Faculty Publications

Schwann cell (SC) transplantation shows promise in treating spinal cord injury as a pro-regenerative agent to allow host endogenous neurons to bridge over the lesion. However, SC transplants face significant oxidative stress facilitated by ROS in the lesion, leading to poor survival. deferoxamine mesylate (DFO) is a neuroprotective agent shown to reduce H₂O₂-induced cell death in serum-containing conditions. Here we show that DFO is not necessary to induce neuroprotection under serum-free conditions by cell survival quantification and phenotypic analysis via immunohistochemistry, Hif1α and collagen IV quantification via whole cell corrected total cell fluorescence, and cell death …

Injection-Related Infections And Self-Treatment Practices Among People Who Inject Drugs In Rural Appalachia, Laura C. Fanucchi, Jennifer R. Havens, Matthew Fahmy, April M. Young

Center on Drug and Alcohol Research Faculty Publications

In this study of self-reported serious injection-related infections among people who inject drugs in rural Appalachia (n = 463), 50% reported reusing syringes/needles, 70.6% ever had an injection-site abscess, and 44.4% of those with a recent abscess took nonprescribed antibiotics. The study identifies opportunities to improve harm reduction services.

Comparison Of Video Modeling And Naturalistic Time Delay For Children With Autism In Preschool Classrooms, Makenna A. Briggs

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

This study presents findings from an alternating adapted treatments design (AATD) that compared the use of video modeling and naturalistic time delay to teach language targets to children with autism. The research included two U.S. preschool students with a provisional diagnosis of autism spectrum disorder (ASD). Both participants met criterion with time delay.

German Cockroach Allergen Mitigation, Olivia Katz

Theses and Dissertations--Entomology

German cockroaches (Blatella germanica L.) remain one of the most challenging indoor pests to manage, due in large part to their cryptic nature, rapid reproduction, and resistance to insecticides. Because of their close proximity to humans, they also pose several serious health threats, including the production and dissemination of several potent allergens linked to asthma development and exacerbation. Given the risks associated with cockroach allergens, we examined the longevity of two distinct cockroach allergens (Bla g 1 and Bla g 5) in the home environment and the efficacy of cleaners at removing these allergens. Our findings show that Bla …

Including Black Farmers, Excluding Pests: Perspectives On Participation In The Cooperative Extension Service, Briana Bazile

Theses and Dissertations--Entomology

In recent years, the U.S. Department of Agriculture has faced renewed scrutiny for documented discrimination against Black farmers, yet far less attention has focused on its century-old partner in public service delivery, the Cooperative Extension Service (CES). This gap is especially notable considering 1) federal parity mandates extant since 1972 in response to significant disparities between Black and White constituents and staff,2) public commitments to Diversity, Equity & Inclusion in 2020 and, 3) the contributions of Black leaders at the origins of CES, at Tuskegee University in the late nineteenth century. Using the Kentucky Cooperative Extension Service (KYCES) as a …

Sedimentary Archives Of Late Quaternary Limnological, Ecological, And Environmental Change In The Eastern Sierra Nevada (California, Usa), Bailee Hodelka

Theses and Dissertations--Earth and Environmental Sciences

The Sierra Nevada essentially serve as the headwaters of California, providing crucial freshwater to the state through seasonal snowmelt. This water supply is threatened by climate change in complex ways that are not fully understood. Geological records provide a valuable source of information on how the hydrology, limnology, and ecology of the Sierra Nevada region has responded to climate changes of the past. This dissertation presents new sedimentary and paleoecological research from Mono Lake and Convict Lake (Mono County, California) and aims to shed light on environmental changes in the eastern Sierra Nevada from ~16 ka to present.

At Mono …

Implications Of Nutrient Fate And Transport Following Nanopesticide Applications In Agricultural Field Plots In Central Kentucky, William Rud, Manuel D. Montaño, Daniel M. Miller, Wayne T. Sanderson, Carmen Agouridis, Brianna F. Benner, Tiffany L. Messer

Biosystems and Agricultural Engineering Faculty Publications

The potential benefits of nanopesticide use over standard pesticides include more precise application at reduced application rates, lower premature degradation, and decreased direct impacts to target organisms. However, field scale investigations of the fate and transport of common nanopesticides such as copper (II) hydroxide and imidacloprid combinations, remain limited. A field study evaluating nano-scale copper (II) hydroxide (Cu), standard imidacloprid (I), nanoimidicloprid (NI), and nano-scale copper (II) hydroxide and imidacloprid (CuNI) compared to control (C) plots was conducted using thirty 14.6 m² field plots to determine the impacts of nanopesticide applications on nutrient cycling and quantify the persistence of …

Folliculin (Flcn) In Thyroid Tumors: Incidence, Significance, And Role As A Driver Gene And Secondary Alteration, Faisal Hassan, Camryn Slone, Robert J. Mcdonald, Julie C. Dueber, Adeel M. Ashraf, Melina Windon, Oliver J. Fackelmayer, Cortney Y. Lee, Therese J. Bocklage, Derek B. Allison

Pathology and Laboratory Medicine Faculty Publications

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (FLCN), best known for its role in Birt–Hogg–Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic FLCN alterations—one germline and one somatic—and analyze the broader prevalence and significance of FLCN in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline FLCN mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma. Molecular testing confirmed biallelic FLCN inactivation, but no additional mutations or aggressive features were observed, and the patient …

Characterizing And Targeting The Non-Catalytic Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) In Oncogenesis And Cancer Progression, Jeffery T. Jolly

Theses and Dissertations--Molecular and Cellular Biochemistry

Phosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity …

La Parole Comme Outil De Résistance Contre Les Tabous Oppressifs Des Femmes Marocaines : Une Étude Comparative De Paroles D’Honneur Et Hshouma, Roseline Adeleke

Students' Supported Scholarship

No abstract provided.

Alzheimer’S Disease And The Immune System: The Emerging Role Of Temra Cells, Edric D. Winford, Adam D. Bachstetter

Neuroscience Faculty Publications

No abstract provided.