Digital Commons Network^™

Heterogeneity Among Harveyi Clade-Specific Virulence Genes And Attribution Of These Genes To Possible Environmental Carriers, Cameron Brown

Biology Theses

In the face of global warming, waterborne pathogens are evolving rapidly and expanding geographically. The Vibrio Harveyi clade encompasses a number of human and aquatic organism pathogens, and due to their physiology, they may benefit from ongoing changes in the temperature, pH, and salinity of the global Ocean. With this, the Southeastern United States might become an accommodating environment for Harveyi clade species, and it is imperative to monitor for their abundance and distribution in the environment. A qPCR assay was developed for the detection and quantification of clade-specific virulence genes toxRvh, hly, toxR, luxR, srp, vhha, vhh, and vhp …

Investigating The Distinct Role Of Pd-L2 In Modulating Human T Cells Responses, Anupallavi Srinivasamani

Dissertations and Theses (Open Access)

INVESTIGATING THE DISTINCT ROLE OF PD-L2 IN MODULATING HUMAN T CELL RESPONSES

Anupallavi Srinivasamani, M.S.

Advisory Professor: Michael A. Curran, Ph.D.

Therapeutic blockade of the Programmed cell death-1 (PD-1) receptor and its ligand Programmed death ligand-1 (PD-L1) has revolutionized the treatment of multiple cancers and made durable tumor regression a possibility in the clinic. PD-1 blockade prolonged progression-free survival and overall survival with lesser high-grade toxicity in patients with advanced melanoma when compared to the other FDA-approved checkpoint blockade target, CTLA-4. Unlike CTLA-4, PD-1 is unique in its ability to regulate T cell functions in lymphoid tissues as well as …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Unveiling Immune Checkpoint Therapy Resistance Mechanisms In The Tumor Microenvironment Using High-Dimensional Analyses, Swetha Anandhan

Dissertations and Theses (Open Access)

The advent of immune checkpoint therapy (ICT) has transformed cancer treatment, but its effectiveness is limited in certain cancers like pancreatic ductal adenocarcinoma (PDAC), which exhibit resistance to this therapy. To overcome this challenge, it is crucial to understand the underlying mechanisms that determine tumor response to ICT and develop rational therapeutic combinations. The tumor microenvironment (TME), including suppressive myeloid cells, regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs), plays a pivotal role in ICT responses. Leveraging single-cell technologies, this study explores the role and function of immune subsets in the TME that induce therapy resistance.

Using single-cell RNA sequencing …

Role Of Il-17/Il-17ra Signaling In The Pancreatic Tumor Microenvironment, Susana Castro Pando, Susana Castro Pando

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths. PDAC is characterized by the early establishment of a highly immunosuppressive fibro-cellular tumor microenvironment (TME). Our research has revealed the important role of IL-17 in the development and progression of pancreatic cancer, yet the specific cellular compartment responsible for IL-17-mediated tumor promotion remains unknown. We generated a transgenic mouse model with pancreatic KrasG12D activation and selective deletion of IL-17RA in the epithelial vs. immune component using either genetic manipulation or bone marrow transplantation. Deletion of IL17RA from the pancreatic epithelial compartment delayed premalignant lesion development …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Digital Hair Creation For Archaeological Facial Approximation: George Dixon, The Last Captain Of The Hl Hunley, Robert Emerson

All Theses

This study explores the application of digital hair creation techniques in archaeological facial approximation, focusing on the case of George Dixon, the last captain of the HL Hunley submarine. While digital hair creation techniques have been previously employed in facial approximation, this research seeks to investigate further their potential and advantages over traditional methods, particularly regarding flexibility and the ability to create multiple variations.

Facial approximation is a critical method for reconstructing the physical appearance of historical individuals. However, accurately recreating their hairstyle presents a significant challenge due to limited information and reliance on artistic interpretation. This research aims to …

Met Alterations In Glioblastoma: Characterization Of Patient-Derived Xenografts And Therapeutic Strategies, Anna Musket

Electronic Theses and Dissertations

Glioblastoma is the most commonly diagnosed central nervous system primary malignancy and it is considered a terminal diagnosis with few treatment options available. Glioblastoma tumors frequently develop treatment resistance due in part to their highly heterogenic nature. The heterogeneity of glioblastoma is partially attributed to the presence of glioma stem-like cells (GSC), which are highly invasive and resistant to chemotherapy and irradiation treatments. Signaling of the receptor tyrosine kinase MET is a known regulator of GSC. Glioblastoma patients have an increasingly poor prognosis that corresponds with increasing MET expression. Both GSC and MET are known to contribute to treatment resistance …

Short-Course Therapy For Urinary Tract Infections In Children: The Scout Randomized Clinical Trial, Theoklis Zaoutis, Nader Shaikh, Brian T Fisher, Susan E Coffin, Sonika Bhatnagar, Kevin J Downes, Jeffrey S Gerber, Timothy R Shope, Judith M Martin, Gysella B Muniz, Michael Green, Jennifer P Nagg, Sage R Myers, Rakesh D Mistry, Shawn O'Connor, Walter Faig, Stephen Black, Elizabeth Rowley, Kellie Liston, Alejandro Hoberman

Faculty, Staff and Student Publications

IMPORTANCE: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI).

OBJECTIVE: To compare the efficacy of standard-course and short-course therapy for children with UTI.

DESIGN, SETTING, PARTICIPANTS: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials.

INTERVENTION: Another …

Contactless Food Ordering System, Rishivar Kumar Goli

Electronic Theses, Projects, and Dissertations

Contactless food ordering has revolutionized the way a customer interacts with restaurants by allowing them to place orders and make transactions. Through these web-based platforms, customers can now browse menus, customize orders, and make payments seamlessly. By scanning the restaurant’s QR code, customers can reserve a table. If the table is available, then automatically it will be reserved. However, if the table is occupied the customer will be added to the waiting list. Once the customer selects desired food then they can securely make payments based on ordered food items. The food will be delivered straight to the customer's table. …

Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama

All Dissertations

Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and cattle. As an extracellular parasite, T. brucei relies on the host’s nutrients to satisfy its growth requirements. The parasite is unusual because it does not uptake most of the host’s lipid species. Instead, T. brucei prefers to perform de novo synthesis of most lipid species. One of the lipid species that T. brucei can both uptake and synthesize is fatty acids. In my thesis work, I investigated the dynamics of fatty acid uptake, metabolism, and utilization of T. brucei. My work starts by determining the …

The Relationship Between Congenital Heart Disease And Infant Mortality In Low- And Middle-Income Countries: A Comprehensive Literature Review, Helen Nneoma Odo

Capstone Experience: Master of Public Health

Congenital heart diseases (CHD) are conditions that are present at birth and can affect the structure of an infant’s heart and the way it works. Millions of children are born each year with congenital heart disease yet screening for CHD is not practiced in Low- and Middle-income countries (LMICs). Studies on access to healthcare for infants with congenital heart disease have not kept pace. This literature review centers on the role of congenital heart disease in infant mortality, its burden, incidence and prevalence in LMICs. The databases of PubMed, Google Scholar and Embase were searched and the selected articles for …

Effects Of Hospital Interventions On Maternal Mortality Rates Of African American Women: A Literature Review, Oluwatosin A. Soyege

Capstone Experience: Master of Public Health

Maternal mortality is a serious health concern and harms society’s economic, physical, and psychological well-being. It is tragic for the woman’s family and community when a woman passes away during pregnancy, at delivery, or shortly after delivery. Hospital interventions are needed to mitigate the social impact of maternal mortality. In the U.S., several initiatives have been enacted to reduce maternal mortality. Fighting racism would also help African American women’s rates of maternal mortality as they are subject to stigma in everyday contexts, during pregnancy and obtaining healthcare, and when obtaining resources and services during pregnancy. This paper reviews the literature …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

With Whom Should One Worship? A Fresh Perspective On John Calvin’S Liturgical Theology Of Physical Proximity And Spiritual Epidemic, Sam Neulsaem Ha

University Faculty Publications and Creative Works

COVID-19 has taught us that whom one surrounds oneself with has a profound influence on one’s well-being. In that light, does whom we worship with matter as well? John Calvin would in fact argue that the people we physically worship with have a great impact on our spiritual life. According to Calvin, if you simply worship with (who he deemed to be) the unrighteous group of people, you will lose your spiritual health or even endanger salvation. This is why he was so insistent on asking the French Protestants to leave France and join him in Geneva. What is striking …

Examining The Association Between Emotional Intelligence, Meaning In Life, Stress, And Burnout Among Preâ??Medical Students In The United States, Nayla Paulina Paulina Bejarano Chacon

Open Access Theses & Dissertations

Background and significance: The Association of American Medical Colleges (AAMC) has estimated that by 2034 there will be a physician shortage of around 124,000 physicians. With burnout being one of the main drivers, it is crucial to assess it. Burnout is characterized by high levels of emotional exhaustion and cynicism and low levels of academic efficacy.There has been substantial research on burnout among healthcare providers across different levels of training; however, few studies have examined burnout among undergraduate students who wish to pursue a graduate degree in healthcare. Given the shortage of healthcare providers in the United States, it is …

Structural Study Of Lsd13 And Lsd14 Type I Modular Polyketide Synthases From The Lasalocid A Biosynthesis Pathway, Dayan Viera

Open Access Theses & Dissertations

Bioactive natural products often possess a complex structure and have a large size which make their chemical synthesis highly challenging. To overcome this challenge, we are developing a biosynthetic method for production of natural products and their analogs. This technology is expected to decrease the synthesis time from years to weeks and reduce the cost of drug production by multiple orders of magnitude. We are investigating the biosynthesis pathway of lasalocid A, an anticancer antibiotic, to develop this technology. Specifically, we aim to characterize the enzymes structurally and biochemically in this pathway, thus paving the way for their rational engineering. …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Telehealth Acceptance And Commitment Therapy For Adolescents With Transdiagnostic Health-Related Anxiety: A Randomized Controlled Trial, Julie M. Petersen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Health-related anxiety is a growing issue to understand how to treat, particularly following the COVID-19 pandemic. Some studies show that a specific type of therapy, acceptance and commitment therapy (ACT), may be beneficial for health anxiety in adults, but this has not yet been tested with adolescents. The present study is a randomized, waitlist-controlled trial of ACT delivered via Zoom for adolescents struggling with health-related anxiety. A total of 30 adolescents (ages 12-17), plus one caretaker each (N = 60), living in Utah and currently struggling with health-related anxiety were enrolled. The majority of caretakers and adolescents were White, non- …

Exploring Versatile Glycosyltransferases From Microorganisms For Natural Product Biosynthesis, Jie Ren

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This dissertation is mainly focused on exploring versatile glycosyltransferases from different microorganisms with the purpose of biosynthesizing bioactive natural product glycosides through microbial fermentation. This engineered biosynthesis approach is environmentally friendly, safe, and efficient compared with plant extraction, chemical synthesis, and enzymatic synthesis. Additionally, we applied these characterized glycosyltransferases as efficient biocatalytic tools to produce novel glycosides to expand the chemical repertoire of nature. These novel compounds showed improved water solubility and some of them exhibited enhanced stability and biological activity, which laid the foundation for the development of new therapeutic agents.

In my dissertation research, I have discovered two …

Development, Roll-Out And Implementation Of An Antimicrobial Resistance Training Curriculum Harmonizes Delivery Of In-Service Training To Healthcare Workers In Kenya, Josiah Njeru, Joshua Odero, Sheilla Chebore, Mungai Ndung’U, Emmanuel Tanui, Evelyn Wesangula, Romona Ndanyi, Susan Githii, R Gunturu, Willy Mwangi

Pathology, East Africa

Background: Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.

Methods: An initial stakeholders’ forum was convened to …

Who Is At Risk For New Hepatitis B Infections Among People With Hiv?, John M Sladic, Barbara S Taylor, Mae Thamer, Karen J Vigil, Onkar Kshirsagar, Anna Taranova, Andrew Mccracken, Carmen G Sanchez, Mamta K Jain

Faculty, Staff and Student Publications

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy.

The Hylefm Gene In Phylefm Of Enterococcus Faecium Is Not Required In Pathogenesis Of Murine Peritonitis, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs–DREADD to activate …

What Covid-19 Tweets Reveal About Risk Perception And Safety Preventative Measures And Behaviors Two Years Into A Pandemic, Elizabeth Vargas

Dissertations

The purpose of this study was to examine individuals Covid-19 risk perceptions two years into a long running pandemic. Data was collected analyzing risk perception and safety preventative measures to understand how individuals communicated risk in a health crisis that lasts more than two years. 116,401 tweets were collected from March 7-18, 2022, and analyzed utilizing a qualitative content analysis design. Four main classes were identified from the data which looked at how individuals perceived risk, how individuals determined risk from information that was shared, what preventative measures individuals were utilizing, and how individuals were living after the SARS-CoV-2 pandemic …

Monitoring, Prophylaxis, And Treatment Of Infections In Patients With Mm Receiving Bispecific Antibody Therapy: Consensus Recommendations From An Expert Panel., Noopur Raje, Kenneth Anderson, Hermann Einsele, Yvonne Efebera, Francesca Gay, Sarah P Hammond, Alexander M Lesokhin, Sagar Lonial, Heinz Ludwig, Philippe Moreau, Krina Patel, Karthik Ramasamy, Maria-Victoria Mateos

Oncology Articles

Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome …

Accelerated Epigenetic Aging In Older Adults With Hiv Disease: Associations With Serostatus, Hiv Clinical Factors, And Health Literacy, Steven Paul Woods, Antonio L Teixeira, Lais B Martins, Gabriel R Fries, Gabriela D Colpo, Natalia P Rocha

Faculty, Staff and Student Publications

The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives …

Encephalitis In Hiv-Infected Adults In The Antiretroviral Therapy Era, Melissa Reimer-Mcatee, Denisse Ramirez, Casey Mcatee, Alejandro Granillo, Rodrigo Hasbun

Faculty, Staff and Student Publications

Introduction: Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis.

Methods: We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV.

Results: We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients …

Do Vaccinations Influence The Development Of Alzheimer Disease?, Avram S Bukhbinder, Yaobin Ling, Kristofer Harris, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

A growing literature supports a protective association between vaccines targeting an array of pathogens (e.g., influenza, pneumococcus, herpes zoster) and the risk of Alzheimer disease (AD). This article discusses the potential underlying mechanisms for this apparent protective effect of immunizations against infectious pathogens on the risk of AD; explores the basic and pharmacoepidemiologic evidence for this association, with particular attention paid to important methodological variations among the epidemiologic studies; and reviews the remaining uncertainties regarding the effects of anti-pathogen vaccines on Alzheimer disease and all-cause dementia, with recommendations for future directions to address those uncertainties.

Burden Of Fatty Liver And Hepatic Fibrosis In Persons With Hiv: A Diverse Cross-Sectional Us Multicenter Study, Samer Gawrieh, Jordan E Lake, Paula Debroy, Julia A Sjoquist, Montreca Robison, Mark Tann, Fatih Akisik, Surya S Bhamidipalli, Chandan K Saha, Kimon Zachary, Gregory K Robbins, Samir K Gupta, Raymond T Chung, Naga Chalasani, Kathleen E Corey

Faculty, Staff and Student Publications

Background aims: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH.

Approach results: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors …

Molluscum Contagiosum: Epidemiology, Considerations, Treatment Options, And Therapeutic Gaps, Adelaide A Hebert, Neal Bhatia, James Q Del Rosso

Faculty, Staff and Student Publications

Molluscum contagiosum (MC) is a viral infection that affects primarily pediatric patients, sexually active young adults, and immunocompromised people of all ages. MC occurs all over the world, making up about one percent of skin disorders and appears to be increasing in prevalence. This cutaneous infection is often associated with atopic dermatitis and is typically self-limiting, although spontaneous resolution can take months to years. Many treatments exist, but only one-a drug-device product using topical cantharidin- is approved by the United States (US) Food and Drug Administration (FDA) for treatment of MC. For many years, there was a lack of an …