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Advancements In Glycogen Detection And Spatial Profiling Reveals A New Therapeutic Path For Ewing Sarcoma: A Non-Traditional Glycogen Storage Disease, Lyndsay E. A. Young

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the primary glucose storage carbohydrate in mammals, and it is synthesized in most tissues. As glycogen architecture modulates its role in metabolism, it is essential to accurately evaluate and quantify glycogen, glycogen phosphate, and chain length of glucose monomers. Simultaneous quantitation of glycogen architecture is challenging. This work describes a highly-sensitive method for the detection of both glycogen-derived glucose and glucose-phosphate esters utilizing gas-chromatography coupled mass spectrometry (GCMS). We then integrated this glycogen quantitation workflow into a routinely utilized metabolomics-based assay. The work presented describes a workflow for the normalization of polar metabolites utilizing amino acids derived from …

Investigating The Roles Of Platelet Bioenergetics In Hemostasis And Thrombosis, Kanakanagavalli Shravani Prakhya

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelets use a series of energy-dependent processes to mediate hemostasis, yet it is unclear which metabolic fuels/pathways are critical for platelet function. Platelets are metabolically flexible, switching between glycolysis and oxidative phosphorylation (OxPhos) depending on oxygen tension and substrate availability. The deletion of GLUT1 and GLUT3 together revealed an essential role in platelet function and hemostasis. To study platelet bioenergetics, we used clot contraction. We created a sensitive and inexpensive method to simultaneously assess clot contraction kinetics to directly compare and define the effects of different treatments or genetic manipulations on platelet function.

Since the pharmacological inhibitors cannot be used …

Data Curation For Modeling Tall Fescue Biomass Dynamics With Dssat-Csm, M. B. Hanson, P. D. Alderman, T. J. Butler, A. Caldeira Rocateli

IGC Proceedings (1977-2023)

While models for predicting forage production are available to aid management decisions for some forage crops, there is limited research for a yield model designed specifically for tall fescue (Schedonorus arundinaceus). Therefore, our objective was to adapt an existing perennial forage model, the Decision Support System for Agrotechnology Transfer Cropping Systems Model (DSSAT-CSM) for predicting forage biomass of tall fescue in the southern Great Plains. To evaluate model performance, there must first be a high level of data manipulation and cleaning. In this project, a cohesive dataset combining biomass, weather, soil, and management data were structured into DSSAT …

Placing The Evolutionary History Of Desmognathus Salamanders In Context: A Phylogeographic Approach, Kara Jones

Theses and Dissertations--Biology

Patterns of genetic variation do not arise in a vacuum but are instead shaped by the interplay between evolutionary forces and ecological constraints. Here, I use a phylogeographic approach to examine the role that ecology played in lineage divergence in the Desmognathus quadramaculatus species complex (Family: Plethodontidae), which consists of three nominal species: D. quadramaculatus, D. marmoratus, and D. folkertsi. Previous phylogenetic studies have shown that individuals from these species do not form clades based on phenotype. My approach to reconciling phylogenetic discordance was two-fold, using (1) genome-wide markers to provide insight into the …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …

Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K. Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M. Kurie, Kevin N. Dalby, Pengyu Ren, G. Andrés Cisneros

Markey Cancer Center Faculty Publications

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross- links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We …

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

Comparison Of Botanical Composition Methods And Change Over Time In Kentucky Pastures, Echo Elizabeth Gotsick

Theses and Dissertations--Plant and Soil Sciences

Botanical composition of pastures has been measured with numerous methods over the last century, but there have been limited direct comparisons between methods. The objective of this study was to compare botanical composition methods, to determine the most accurate and efficient method, and to access pasture composition change over time. Six farms with two pastures each were monitored across the state of Kentucky. Sampling occurred fall 2020 through fall 2022, three times a year using the following methods: step point, visual estimation, occupancy grid, and point quadrat (used as a reference method). The occupancy grid showed the highest similarity to …

Black Women And The Weight Of The World: When The Weight Becomes Too Much To Bear, April R. Edmonds

DSW Capstone Projects

ABSTRACT

Black women’s mental health continues to go largely underrepresented. Black women are seen as having many protective factors such as their faith communities, family and friends, and what others see as strength and resilience. A review of the literature depicts Black women as traditionally being caretakers, nurturers, and depicted as strong (Castelin & White, 2022). Because of this perception, terms such as the Strong Black Woman Schema and the Black Superwoman Phenomena are what many equate Black women with. This scholarship instead shows how associations such as these impact Black women negatively and impose additional stigma and hardship. Research …

A Phase Change Memory And Dram Based Framework For Energy-Efficient And High-Speed In-Memory Stochastic Computing, Supreeth Mysore

Theses and Dissertations--Electrical and Computer Engineering

Convolutional Neural Networks (CNNs) have proven to be highly effective in various fields related to Artificial Intelligence (AI) and Machine Learning (ML). However, the significant computational and memory requirements of CNNs make their processing highly compute and memory-intensive. In particular, the multiply-accumulate (MAC) operation, which is a fundamental building block of CNNs, requires enormous arithmetic operations. As the input dataset size increases, the traditional processor-centric von-Neumann computing architecture becomes ill-suited for CNN-based applications. This results in exponentially higher latency and energy costs, making the processing of CNNs highly challenging.

To overcome these challenges, researchers have explored the Processing-In Memory (PIM) …

A Flexible Photonic Reduction Network Architecture For Spatial Gemm Accelerators For Deep Learning, Bobby Bose

Theses and Dissertations--Electrical and Computer Engineering

As deep neural network (DNN) models increase significantly in complexity and size, it has become important to increase the computing capability of specialized hardware architectures typically used for DNN processing. The major linear operations of DNNs, which comprise the fully connected and convolution layers, are commonly converted into general matrix-matrix multiplication (GEMM) operations for acceleration. Specialized GEMM accelerators are typically employed to implement these GEMM operations, where a GEMM operation is decomposed into multiple vector-dot-product operations that run in parallel. A common challenge that arises in modern DNNs is the mismatch between the matrices used for GEMM operations and the …

Application Of Conventional Feedforward And Deep Neural Networks To Power Distribution System State Estimation And State Forecasting, James Paul Carmichael

Theses and Dissertations--Electrical and Computer Engineering

Classical neural networks such as feedforward multilayer perceptron models (MLPs) are well established as universal approximators and as such, show promise in applications such as static state estimation in power transmission systems. This research investigates the application of conventional neural networks (MLPs) and deep learning based models such as convolutional neural networks (CNNs) and long short-term memory networks (LSTMs) to mitigate challenges in power distribution system state estimation and forecasting based upon conventional analytic methods. The ability of MLPs to perform regression to perform power system state estimation will be investigated. MLPs are considered based upon their promise to learn …

Modeling The Early Visual System, Nicholas Lanning

Theses and Dissertations--Electrical and Computer Engineering

There are two encoding schema present in simple cells in the early visual system of vertebrates: the retinal simple cells activate highly when the receptive field contains a center surround stimulus, while the primary visual cortex’s (V1) simple cells activate highly when the receptive field contains visual edges. Work has been done in the past to enforce constraints on visual machine learning such that the retinal or V1 encoding is learned, but this work is often done to emulate retinal and V1 encoding in a vacuum. Recent work using convolutional neural networks focuses on anatomical constraints along with a supervised …

An Interprofessional Collaboration To Increase Total Enteral Nutrition In Critically Ill Patients On Vasopressor Agents In Cvicu, Priyanka Shah

DNP Projects

Background: Delayed enteral nutrition (EN) in critically ill patients increases the risk of complications and poor outcomes. The 2016 American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and Society of Critical Care Medicine (S.C.C.M.) evidence-based guideline recommends initiating EN within 24-48 hours of Intensive Care Unit (ICU) admission once resuscitation and hemodynamically stability have been achieved. The evidence-based guideline notes that critically ill patients on low-dose vasopressors can be started on EN with close monitoring.

Purpose: This interprofessional project aims to increase the amount of EN delivered to all qualifying Cardiovascular Intensive Care Unit (CVICU) patients who are at risk …

Evaluating The Effectiveness Of Family-Based Treatment Education On Provider's Knowledge, Anticipatory Use, And Attitudes Who Treat Adolescent Patients Diagnosed With Anorexia Nervosa, Treven Back

DNP Projects

Background. Anorexia Nervosa is a chronic, disabling, and costly disease with a higher mortality rate than any other psychiatric illness. Because of the need for medical, psychiatric, and nutritional care, treatment is complex. The current literature supports Family-Based Treatment as a first-line treatment for adolescent patients diagnosed with Anorexia Nervosa. However, a gap exists between translating family-based treatments into clinical practice. Literature shows that education and understanding providers' attitudes and beliefs are the first steps to successfully implementing family-based treatments.

Purpose. This DNP project aimed to evaluate the effectiveness of a family-based treatment education intervention on providers' attitudes, knowledge, and …

Assessing Palliative Care Knowledge Among Medicine/Pulmonary Intensive Care Unit Staff To Identify Barriers And Increase Palliative Care Referrals, Ryan Mckendrick

DNP Projects

Background: To conduct a needs assessment to identify areas of opportunity for increased awareness of the interdisciplinary medicine/pulmonary intensive care unit (MICU) staffs’ knowledge of palliative care and identify potential barriers to initiating referrals for palliative care consultations. Then provide an educational intervention and assess effectiveness with a post interventions assessment of referrals. The goal of this project is to increase referrals for palliative care consults.

Methods: A pre-/post-survey design will be utilized to assess palliative care knowledge to identify barriers to palliative care consultation referrals. An educational intervention that addresses palliative care knowledge deficits and addresses barriers will be …

Evaluating Kentucky Advanced Practice Registered Nurses’ Confidence, Comfort, And Knowledge Levels Regarding Dermatology Care After A Web-Based Video Training, Victoria Hayden

DNP Projects

Background: It can take an average of 38.9 days to see dermatology from referral to initial appointment. As a result, delays in diagnosis and treatment of life-threatening conditions such as malignant melanoma could occur. Primary care providers frequently refer patients for benign conditions that can be appropriately managed in the primary care setting; often due to lack of knowledge or confidence in their clinical management skills. Educational resources equip providers with the knowledge and tools to feel confident in their management of various skin conditions in a primary care setting. Purpose: The purpose of this project was to …

Impact Of Physical Activity Vital Sign Screening On Physical Activity Counseling And Referrals In Primary Care, Anna Selepina

DNP Projects

Background/Purpose: Physical Activity Guidelines for Americans recommend 150-300 minutes of moderate-intensity physical activity each week for adults; however, half of the adults do not meet this goal, which leads to increased chronic health conditions and poor health outcomes. The physical activity vital sign (PAVS) screening tool is an evidence-based assessment tool associated with increased physical activity counseling, which can lead to increased physical activity and improved patient outcomes.

Objective: The purpose of this study was to examine the impact of PAVS screening on physical activity counseling and referrals in primary care.

Methods: This prospective study took place in a small …

Evaluating The Effect Of Electronic Health Record Patient Portal Use On Medication Adherence In Adults With Chronic Conditions, Jennifer Averbeck

DNP Projects

Background Medication non-adherence is prevalent among fifty percent of the United States population. This behavior leads to increased morbidity and mortality as well as increased healthcare costs for both the patient and the healthcare system. More than two-thirds of nonadherence exists in those aged over 65 years old who are diagnosed with Multiple Chronic Conditions (MCC). Several studies have researched and trialed interventions to improve rates of adherence, limit poor health outcomes, and decrease overall cost of care. The patient portal is an interactive tool which encourages participation of the patient in their healthcare management. Implementation of this tool has …

Knowledge & Attitudes Towards Pediatric Pain With Needle-Based Procedures In The Emergency Department Setting, Charlstyn Paige Brown

DNP Projects

PURPOSE: By the time a child enters kindergarten, they may have faced as many as thirty-three vaccine-related injections. Throughout these experiences, parents and patients associated pain and fear regarding the administration of multiple vaccines concurrently to a child has played a role in vaccine hesitancy and refusal. Parents and patients experience associated fear and pain regarding the administration of multiple concurrent scheduled vaccines, thus leading to vaccination hesitancy and refusal. In addition to scheduled immunizations, there is also the possibility of unexpected needle-based procedures taking place when emergencies arise. The purpose of the study is to explore the current …

Improving Nursing Comfort In Relation To Difficult Conversations, Sarah Clifton

DNP Projects

Abstract

Background/Purpose

Conversations between care providers and patients are integral to medicine and are the most performed “procedure” (Luff et al., 2016). In Pediatric Intensive Care Units (PICUs) and Pediatric Cardiac Intensive Care Units (PCICUs), children of all ages with diverse diagnoses and needs are treated for critical illnesses and traumatic events. Therefore, providers frequently have difficult conversations with patients and their families. Pediatric critical care nurses are often invited to participate in these discussions. However, their role during, and after, these conversations is not always clear. The goal of this project was to evaluate the impact of an educational …

Implementation Of A Death Anxiety Screening Protocol Specific To Patients With Advanced Cancer In An Outpatient Palliative Care Setting, Olivia M. Sasdi

DNP Projects

Abstract

Background: Recent studies have shown that upwards of 80% of patients with advanced cancer suffer from death anxiety resulting in increased physical and psychological suffering. Despite death anxiety’s ubiquitous nature and negative impact, the literature regarding this condition consistently indicates that it remains under-identified and undertreated in patients with advanced cancer. The “Death and Dying Distress Scale” (DADDS) is a clinically validated tool used to identify, measure, and guide effective treatment modalities for death anxiety specifically in patients with advanced cancer, but is scarcely used routinely in practice. Incorporating this screening tool to be used regularly could improve identification …

Effectiveness Of A Multimodal Educational Program In Increasing Understanding And Utilization Of Tele-Icu Resources By Critical Care Nurses: A Pilot Study, Olga Vulakh

DNP Projects

Background. Integration of tele-intensive care units (tele-ICUs) into healthcare systems is associated with improved patient outcomes and organizational performance. Inadequate bedside nurses’ knowledge about tele-ICU is associated with poor communication and lack of trust between bedside and tele-ICU teams. These problems might diminish tele-ICU’s ability to maximally impact patient outcomes.

Purpose. The purpose of this project was to create a multimodal educational program with the goal of improving knowledge, attitudes, and skills related to tele-ICU among critical care nurses and to assess the effect of the educational intervention on tele-ICU utilization among bedside nurses as evidenced by the number of …

Relationship Between Number Of Mechanical Ventilation Days Prior To Ecmo Initiation And Outcomes In Covid-19 Patients, Brittany Bergman

DNP Projects

Background: Since the start of the pandemic, there has been over 16,000 COVID-19 positive patients placed on Extracorporeal Membrane Oxygenation (ECMO). Little is known about the effect of long mechanical ventilation prior to ECMO initiation. Purpose: The first purpose of this project is to evaluate whether a longer mechanical ventilator time (ten or more days) prior to ECMO initiation is associated with increased mortality and longer total lengths of time on ECMO in patients with COVID-19, as opposed to being on a ventilator for under ten days prior to being placed on ECMO. The second purpose is to increase provider …

Utilizing Podcast Education To Improve Nurse Knowledge, Confidence, And Behaviors Related To Palliative Care Conversations In The Intensive Care Unit, Brittany Estridge

DNP Projects

Background: The personal connection that Registered Nurses (RNs) build with patients and their families puts them at the forefront of many conversations during the patient’s stay in the intensive care unit (ICU). Some of the most difficult conversations are related to palliative care (PC). It can be challenging to know how to respond to the complex questions posed in palliative care conversations (PCC) when patients and their caregivers are making decisions that will alter the course of the patient’s treatment, as well as affect the quality and length of their life.

Purpose: Nurses receive inadequate training in PCC. The purpose …

Modified Early Warning Scoring (Mews) Versus Epic Deterioration Index (Edi): Battle Royale For Which Has The Best Patient Outcomes In The Inpatient Setting, Dirk A. Church

DNP Projects

Abstract

Background: The increased workload bedside nurses face today requires new tools to assist with the identification of deteriorating patients during hospitalization. The Modified Early Warning Score (MEWS) tool has formed the background of early warning tools. Newer, more complex tools, like Epic’s Deterioration Index (EDI), have been developed to identify patient deterioration earlier. There is lack of evidence in the literature comparing different early warning tools, implementation, and patient outcomes.

Objective: The purpose of the study was to examine models for EWS notification for RRT and patient outcomes between the use of the MEWS and EDI in an adult, …

Building A Kentucky Baguette: Agronomic Traits, Bread Baking Quality Measurements, And Sensory Evaluation Of Modern And Landrace Wheat Cultivars Grown Under Conventional And Organic Nitrogen Management, Bryan Brady

Theses and Dissertations--Plant and Soil Sciences

The demand by artisan bread bakers across the United States for local wheat varieties has increased in recent years. The southeast is traditionally a soft winter wheat (SWW) region, producing low gluten flours more suitable for biscuits and cookies. Recently, hard winter wheat (HWW) varieties have been bred to produce acceptable yields in the high humidity environment of the southeastern United States. Artisan bread bakers in Kentucky would like to create a niche food value chain benefitting farmers, small-scale millers, bakers, consumers, and their local and regional food systems (LRFS). The increased demand and the availability of adapted hard wheat …

Application Of Multi-Scale Computational Techniques To Complex Materials Systems, Mujan N. Seif

Theses and Dissertations--Chemical and Materials Engineering

The applications of computational materials science are ever-increasing, connecting fields far beyond traditional subfields in materials science. This dissertation demonstrates the broad scope of multi-scale computational techniques by investigating multiple unrelated complex material systems, namely scandate thermionic cathodes and the metallic foam component of micrometeoroid and orbital debris (MMOD) shielding. Sc-containing "scandate" cathodes have been widely reported to exhibit superior properties compared to previous thermionic cathodes; however, knowledge of their precise operating mechanism remains elusive. Here, quantum mechanical calculations were utilized to map the phase space of stable, highly-faceted and chemically-complex W nanoparticles, accounting for both finite temperature and chemical …

Developing And Modeling Tunable Nanofiltration And Functionalized Membranes For The Separation Of Organics And Inorganics From Water: Per- And Polyfluoroalkyl Substances, Lanthanides, And More, Francisco Cecil Leniz-Pizarro

Theses and Dissertations--Chemical and Materials Engineering

In a world where clean water predictability is challenged by both global warming and the contamination of our natural resources, it is our responsibility to advance water separation technologies into more efficient processes and to lessen their environmental footprint. Pore and surface functionalization of membranes can enhance the separation of ions from water and even help overcome intrinsic challenges that some current separation technologies possess. If we begin with a complete fundamental understanding of the nanoscale interactions that occur in the process of separating ions from water, then we can engineer new functionalized composite membranes to provide alternative processes keeping …