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The Role Of Tumor Microenvironment In Glioblastoma Multiforme(Gbm) Therapeutic Resistance, Kwesi E. Taylor

Master's Theses or Doctor of Nursing Practice

Despite significant advances in cancer research and treatment, Glioblastoma multiforme (GBM) remains one of the most difficult cancers to treat effectively, with minimal improvement in long-term survival rates over the past few decades. This is largely attributed to tumor heterogeneity and the ability of tumor cells to develop adaptive resistance mechanisms supported by the tumor microenvironment (TME). Although the TME is recognized as a key contributor to tumor progression and therapeutic resistance, the underlying molecular pathways and regulatory genes remain incompletely understood. This study investigated the role of the tumor microenvironment in GBM therapeutic resistance using a bioinformatics approach. Single-cell …

Bayesian Multivariate Modelling Of Lone Star (Amblyomma Americanum) Tick Life Stage Abundance And Temporal Trends To Inform Public Health Risk In Virginia, Thabo Lephoto, Henry Mwambi, Oliver Bodhlyera, Holly Gaff

Biological Sciences Faculty Publications

The increasing abundance of ticks poses a growing public health concern due to heightened human exposure to tick bites. The lone star tick (Amblyomma americanum: Ixodida: Ixodidae), a common human-biting species in the United States, has expanded its range in recent years. However, how its different life stages vary across time, habitats, and locations remains insufficiently understood. We analyzed tick abundance data collected in southeastern Virginia between 2009 and 2018, focusing on larval, nymphal, and adult life stages. A Bayesian multivariate modelling framework was used to examine seasonal patterns, habitat effects, spatial variation, and biological links between life stages. Two …

The Rhesus Macaque Model Of Mycobacterium Avium Infection Reveals That Age-Related Disease Is Due In Part To Chronic Inflammation And Lung Microbial Dysbiosis, Ethan G. Napier

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Aging is associated with dysregulated immunity and increased susceptibility to infection, a phenomenon dubbed as immunosenescence and characterized by reduced naïve T and B cell pools, altered innate immune function, and chronic low-grade inflammation. Nontuberculous mycobacterial (NTM) pulmonary disease (NTMPD) is an increasingly relevant chronic lung infection that disproportionately affects older adults (65+ years) and immunocompromised individuals. However, the host factors underlying increased disease severity in aged patients remain poorly defined. Literature suggests that effective control of NTM relies on coordinated innate and adaptive immune responses, particularly macrophage activation and Th1 cytokine signaling. Using a rhesus macaque model that closely …

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 …

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 …

Roles Of Cytokines In Modulating Trypanosoma Brucei Rhodesiense Infection Outcomes In Vervet Monkeys, Clarah Jebet, John Kibuthu Thuita, Daniel Masiga, Benedict Owino Orindi, John Oidho, Mark C. Field, Enock Matovu, Vincent Owino Adung’A

All Peer-Reviewed Publications

Introduction:

Human African trypanosomiasis (HAT), caused by Trypanosoma brucei rhodesiense, is categorized as acute due to rapid disease progression but presents varying clinical outcomes. Although the mechanisms underpinning differential clinical progression are poorly understood, both host and parasite factors are implicated. Therefore, we sought to elucidate roles of primate host factors in mediating varying T. b. rhodesiense infection outcomes.

Methods:

Here, we assessed the roles of selected host cytokines in disease progression using a tsetse-mediated infection in a non-human primate (NHP) vervet monkey model that closely mimics HAT and natural infection. We quantified eight cytokines, including TNF-α, IFN-γ, IL-10, IL-6, …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

An Assessment Of Disease Risks, Population Genetics, And Spatial Ecology Of Appalachian Cottontails (Sylvilagus Obscurus) And Snowshoe Hares (Lepus Americanus) In West Virginia, Usa, Madison Leigh Miller

Graduate Theses, Dissertations, and Problem Reports (ETD)

Snowshoe hares (Lepus americanus) occupy a large range across the United States and Canada. While snowshoe hare populations are generally considered stable in the interior of their range, populations along range edges are experiencing declines, possibly driven by climate-related factors such as seasonal coat color mismatch. West Virginia represents one of the southernmost extents of the species’ range, yet little is known about the population genetic status or population sizes of snowshoe hares in the state. Appalachian cottontails (Sylvilagus obscurus) are another lagomorph species found in West Virginia. This species experienced a historical decline and currently …

Dielectrophoretic Biomarkers For Cancer Detection And Cell Analysis: Integrating Microfluidics And Ai, Raphael Olumide Oladokun

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pancreatic ductal adenocarcinoma (PDAC) carries a five-year survival rate of 13%, driven largely by late-stage diagnosis and the absence of sensitive noninvasive screening tools. Current diagnostic methods lack the sensitivity to detect disease-associated systemic changes at early and precancerous stages, representing a critical clinical gap. This dissertation addresses the central hypothesis that PDAC and its pathological subtypes induce measurable, disease-associated electrophysiological changes in circulating PBMCs that can serve as correlative liquid-biopsy biomarkers. To test this hypothesis, this work asks: can dielectrophoresis (DEP), impedance and zeta potential analysis with AI-assisted classification distinguish benign pancreatic conditions (non-malignant control), precancerous lesions (primarily IPMNs), …

Repurposing Cyclin-Dependent Kinase Inhibitors For The Discovery Of Novel Antiplasmodial Compounds, Ritam Bhowmik

Honors Undergraduate Theses

Malaria remains a major global health burden with over 282 million cases annually and rising resistance to artemisinin-based combination therapies. Plasmodium falciparum, the most lethal malaria parasite species in humans, relies on tightly regulated cell cycle progression during replication within red blood cells. Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell division and transcription, and several CDK-like enzymes in P. falciparum, including Pfmrk and PfPK6, are essential for parasite growth and structurally distinct from human kinases. This study evaluated whether commercially available human CDK inhibitors (CDKIs) targeting cancer pathways could be repurposed as novel antimalarial compounds. A library of …

Impact Of Lifestyle Factors On Allergic Rhinitis Symptoms And Quality Of Life Among College Students, Lina Saint-Hilaire

Honors Undergraduate Theses

This study aims to examine the influence of certain lifestyle factors on the presentation of allergic rhinitis symptoms and the quality of life of college students. Factors of interest include residential setting, household cleaning habits, age of symptom onset, and exposure to household pets. Additional analysis includes assessment of the impact of allergic rhinitis symptoms on sleep. Using a cross-sectional survey design, student responses were self-reported through a paper survey distributed during tabling days at the University of Central Florida (UCF) main campus. Eligible participants had to be 18 years or older and current UCF graduate and undergraduate students. Survey …

Impact Of Prostate Cancer Tumor Microenvironment On Alternative Splicing Landscapes In Nk Cells: An Lncap-Based In Vitro Model, Pratham N. Modi

Honors Undergraduate Theses

NK cells play a significant role in anti-tumor activity, yet the transcriptomic mechanisms underlying NK cell dysfunction in the prostate cancer tumor microenvironment remain generally poorly characterized. While most transcriptomic studies focus on gene-level expression, alternative splicing and isoform-level analysis may reveal additional levels of regulation not identified in traditional analysis. The overall goal of this study was to characterize gene and isoform-level changes in NK cells exposed to in vitro prostate cancer conditions and to evaluate whether isoform-level analysis could provide additional depth and insights beyond gene-level analyses. NK92-MI cells were co-cultured with LNCaP prostate cancer cells using direct-contact …

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …

Development Of A Split Deoxyribozyme-Based Assay For Detecting Hepatitis B Virus, Dalila Zovko

Honors Undergraduate Theses

Rapid, accessible nucleic acid-based detection methods are needed for hepatitis B virus (HBV). A split deoxyribozyme assay was developed for sequence-specific fluorescence detection. The assay was evaluated using synthetic target and plasmid-derived material. The assay showed target-dependent fluorescence and low-concentration linear range with a LOD of 1.9 nM. The assay supports detection and semi-quantification of HBV genetic material as shown using plasmid-derived transcript samples from HBV genotypes B, C, and D. The selected target corresponded to nt 363–406 of the HBV genome and was chosen based on sequence alignment showing conservation across most genotypes. Genotype-specific detection remains a future application …

Analysis Of Alternative Gene Splicing Of Natural Killer Cell Exhaustion Markers During Siv Infection, Soledad B. Zayas

Honors Undergraduate Theses

Natural killer cells play a critical role in the innate immune response against Human Immunodeficiency Virus and Simian Immunodeficiency Virus infections. During HIV/SIV infection, NK cells undergo functional impairment characterized by an imbalance between activating and inhibitory surface receptors. The upregulation of inhibitory receptors, TIGIT and TIM-3, has proven to contribute to NK cell exhaustion during different retroviral infections. Although alternative splicing regulates immunity related genes, its role in TIGIT and TIM-3 expression during SIV infection remains poorly understood. This study aimed to characterize alternative splicing patterns of TIGIT and TIM-3 and evaluate transcript variant expression during SIV infection in …

Nanoparticle Carriers Enhance The Prophylactic Antiviral Effects Of Dsrna In Vitro And Ex Vivo, Shayne Oberhoffner, Stephanie Dewitte-Orr, Starla Richardson, Leah Haile, Dominique Daniels, Erin Cooper, Aizah Ijaz, Janet Velasquez Perez, Mathilde Peruzzi, Bertrand Collet, Paul Craig, Kristof Jenik

Theses and Dissertations (Comprehensive)

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a …

Investigating The Immunostimulatory Potential Of Dsrna-Silk Nanoparticle Complexes In Melanoma, Samuel J. Peters

Theses and Dissertations (Comprehensive)

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they …

Ovarian Cancer Immunology And Immunotherapy: Editorial Note, Chris D. Platsoucas

Biological Sciences Faculty Publications

[Introduction] As the guest editor of the Special Issue on Ovarian Cancer Immunology Immunotherapy, I would like to include certain brief comments on the current state of the field and to introduce the Special Issue. Ovarian carcinoma and malignant melanoma are the first human tumors where immune responses, primarily restricted to autologous tumor cells, were first demonstrated. T-cell lines and clones developed in recombinant interleukin-2 (rIL-2) from tumor-infiltrating lymphocytes (TIL) from these tumors exhibited cytotoxicity and/or cytokine production, primarily restricted to autologous tumor cells. The T-cell receptor (TCR) and the CD3 differentiation antigen on effector T cells and HLA on …

Effects Of Desiccation On Invasive Faucet Snail (Bithynia Tentaculata) And Trematode Survival, Elise Marie Jordahl

Graduate Research Theses & Dissertations

Parasitism is one of the most common and diverse life history strategies, yet relatively little is known about the role of parasites as invasive species. Invasive species, which present one of the greatest threats to biodiversity, often need to overcome adverse environmental conditions as they establish and spread in new habitats. Invasive parasites are subject to these same conditions, though the effects may be mediated through their hosts. Here, I use an invasive snail and its trematode parasites to quantify the effects of desiccation on survival to better understand how processes of invasion play out in host-parasite systems. The faucet …

The Effect Of Sex On A-To-I Editing In Skeletal Muscle During Inflammation, Skyler Lee

Graduate Theses/Dissertations

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional mechanism mediated by ADAR enzymes that can alter RNA sequence, protein function, and gene regulation. Because ADAR1 is upregulated during inflammation and plays a critical role in innate immunity, previous studies investigated the effects of acute inflammation on RNA editing in male and female mice. Lipopolysaccharide (LPS) was used to induce inflammation, and RNA editing levels were examined in the heart, brain, and skeletal muscle. While editing levels in the heart and brain remained unchanged, skeletal muscle exhibited tissue- and sex-specific differences in editing. In this thesis, LPS treatment affected selective editing, increasing …

Larval Crowding In Culex Pipiens Generates Cumulative Cascading Effects Under Changing Environmental Conditions, Sengul Talay, Zafer Sakaci, Michele C. Weigle, Bugrahan Regaip Kilinc, Jenah Parman, Holly Gaff, Deniz Sirin, Bulent Alten, Dennis Bente, Sirri Kar

Computer Science Faculty Publications

Density-dependent population regulation is a fundamental driver in the population dynamics of living systems, ensuring a balanced and sustainable maintenance in nature. It has been suggested that the adverse developmental and morphological effect of high larval density in container mosquitoes represents a significant limiting factor for population density, and the need to investigate this possible importance within the framework of field-based principles has been emphasized. This semi-field study, conducted under the natural thermal regime and using a natural population in Turkish Thrace, aimed to examine the effects of non-food-limiting larval density (crowding effect) in the mosquito species, Culex pipiens ( …

Investigating The Potential Neurotoxic Effects Of Cell-Free Factors By Batrachochytrium Dendrobatidis On Locomotion In Xenopus Laevis, Anna Lennon, Laura K. Reinert, Louise A. Rollins-Smith, Will Best, Chase T. Kinsey Phd

Funded Scholarship

Chytridiomycosis is a contributor to amphibian population declines. Diseased amphibians show symptoms of lethargy and loss of righting reflexes, likely due to ion imbalance across the skin. However, it is possible developing zoosporangia release toxins that affect neuromuscular activity. Using Xenopus laevis as a model, we hypothesized that locomotor performance would be affected by injection of Bd supernatant factors. X. laevis were injected and then filmed performing a swimming escape response with high-speed cameras at 4 hours, 24 hours, and 1- week post-injection. Average maximum swimming velocity and escape latency were digitized using high speed video. Despite no difference in …

Drug-Induced Lichen Planus Associated With Ocrelizumab, Avery Seward, John D. Strickley, Jeffrey P. Callen

Department of Medicine Faculty Publications

This case report highlights recurrent cutaneous lichen planus as a rare adverse effect of ocrelizumab, with flares occurring after each infusion and improving with prophylactic prednisone. Recognizing this association may help clinicians diagnose and manage similar cases while allowing patients to continue an otherwise effective therapy.

Sexual Dimorphism In The Immune Defense Mechanisms Against A Systemic Bacterial Infection In The Cat Flea (Ctenocephalides Felis), Ashley Lynch

College of Graduate Studies: Theses & Dissertations

Fleas defend against infection through the activation of both humoral and cellular innate immune responses. Previous research in female cat fleas demonstrated increased immune activity following a systemic bacterial infection. However, comparable data for males and sex-based comparisons are limited. In this study, we investigated differences in innate cellular immune responses between male and female cat fleas following systemic infection with Gram-negative Escherichia coli. Bacterial load was quantified using colony-forming units 24 h post-infection. Immune function was assessed via phagocytic index and capacity. Survival and total circulating hemocyte counts were evaluated across infected, sterile-injected, and untreated groups. Male fleas …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …

Prevalence Of Dengue Infection In Bangladesh: A Systematic Review And Meta-Analysis, Md. Estiar Rahman, Abdullah Al-Taiar, May Salama, Michele A. Kekeh, Ahmed N. Albatineh

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Objective: 

To estimate the pooled prevalence of dengue infection in Bangladesh.

Methods:

Literature search was conducted across PubMed, Web of Science, and Hinari between December 2024 and April 2025, supplemented by references searching. The Joanna Briggs Institute checklist was used for evaluating study quality. A random effects meta-analysis of proportion, including subgroup analyses, was performed with R software (version 4.5.1).

Results:

Out of 2 087 records, 28 studies were included. The pooled prevalence of confirmed dengue infection among clinically suspected patients was 49.3% (95% Cl 36.1-62.6), with a significant high heterogeneity (I²=99.2%, τ²=1.81, P< 0.001). Stratified analysis showed a pooled prevalence of 47.9% (95% Cl 34.0-62.2, I2=99.1%, …

Inflammation In Early Borrelia Burgdorferi Skin Infection, Ariana Nobles

Electronic Theses & Dissertations (2024 - present)

Borrelia burgdorferi (Bb) is the causative agent of approximately 476,000 cases of Lyme disease in the United States and rising. Bb is spread through infected saliva of the black-legged tick, Ixodes scapularis, to the host. Patients infected with Bb experience short-term symptoms, such as erythema migrans (EMs), fatigue, pain, and cognitive impairment. If left untreated, Bb infection will cause long-term health complications, like Lyme neuroborreliosis and Lyme arthritis. It is postulated that symptoms associated with Lyme disease are driven in part by inflammation.

My thesis focuses on the skin as it holds significant immunological importance in the …

Development And Applications Of Fluorescence Microscopy Protocol To Investigate Borrelia Burgdorferi Immune Interactions In The Skin, Rebecca V. Landry

Electronic Theses & Dissertations (2024 - present)

The skin is an immunological organ that acts as the hosts’ first line of defense against infectious agents. Infectious disease vectors like ticks breach this barrier by feeding on hosts, transmitting pathogens like Borrelia burgdorferi in the process. Uncleared infection with B. burgdorferi causes Lyme disease, the most prevalent vector-borne disease in the United States. Previous research has explained many elements of Lyme disease pathogenesis and immunity including the dissemination of the spirochete, innate immune cells performing phagocytosis, the production of antibodies by the humoral response, and the impact of prophylactic treatment with monoclonal antibodies. A remaining gap in the …

Developing A Tool To Measure Resistance To Sustainable Food Choices: A Pilot Study In Ireland And The Netherlands, Kate Flanagan, Bart Sinteur, Patricia J. Bulsing, John M. Kearney

SURE Journal: Science Undergraduate Research Experience Journal

Consumer uptake of a sustainable diet is critical for addressing environmental challenges and promoting public health. Understanding why consumers resist adopting sustainable eating habits can inform targeted interventions and policies. This pilot study examines whether a newly developed scale can effectively detect consumer resistance to a sustainable diet. Currently, there is a lack of research on a tool to measure consumer resistance to a sustainable diet, highlighting the need for a reliable instrument.

The aim of this study is to develop a scale, based on existing literature, to measure consumer resistance to a sustainable diet. Additionally, the study aims to …

Editorial-Sure Journal Volume 7, Issue 2, Geraldine M. Dowling, Eva Campion, Sinead Loughran, Ariane Perez-Gavilan, Josephine Treacy

SURE Journal: Science Undergraduate Research Experience Journal

No abstract provided.