Medicine and Health Sciences Commons^™

Exploration Of Breastfeeding As A Protective Factor For Breast Cancer In South African Women: A Nested Case-Control Study, Booker S. Quiera

Dissertations and Theses (Open Access)

Background. South African’s (SA) breast cancer incidence rate is continually increasing (39 per 100,000 (2012) versus 46.2 per 100,000 (2018) with trends towards later-stage diagnosis. In previous literature, breastfeeding has been assessed as a protective factor for breast cancer; however, the SA population experiences inconsistent breastfeeding trends, rates, and support services. Therefore, this study will evaluate the inverse association between breast cancer and breastfeeding history. Methods. Cases (breast cancer) and controls (mastalgia) were matched 1:1 on clinical visit from May-August 2019 at Groote Schuur Hospital (GSH) in Cape Town, Western Cape, South Africa. Breastfeeding history, breast carcinoma diagnosis, and clinically …

The Influence Of Sodium And Potassium On Blood Pressure Genetics In The Population Architecture Using Genomics And Epidemiology Study, Cynthia S. Bell

Dissertations and Theses (Open Access)

Multiple polymorphisms have shown associations with blood pressure (BP) levels and hypertension status, but the overall genetic effect on BP has been small and accounts for only a small fraction of the variation in population-wide BP characteristics. These weak associations of BP with genotype may not be attributable to the examining the “wrong” single nucleotide polymorphism (SNP) but may instead be the result of noisy BP phenotypes based on mmHg alone. Adding information from the underlying mechanisms of nutritional intake, reuptake, and excretion on BP may produce more informative BP phenotypes to study. To explore this complex relationship between diet, …

Estimating Children’S Health Risks From Recreational Beach Play Following An Oil Spill, Tanu K. Altomare

Dissertations and Theses (Open Access)

Environmental contamination from marine oil spills can have damaging impacts on ecosystems and human health. In 2010, an explosion of the Deepwater Horizon (DWH) oil drilling platform resulted in approximately 1,728 km of shoreline oiling. Existing research characterizes health risk from exposure to oil spill chemicals (OSCs) for adults; however, data on impacts to child health are limited. One objective of the Beach Exposure And Child HEalth Study (BEACHES), funded by the Gulf of Mexico Research Initiative, is to estimate health risks to children between walking and six years of age from exposure to OSCs in a post-oil spill scenario …

Measuring Cultural Humility Of Community Health Workers, Nayeema Ahmed

Dissertations and Theses (Open Access)

This study examined cultural humility of community health workers (CHWs) in ambulatory clinical settings. Cultural humility has been defined as an attitude, or process that incorporates openness, power-balance, and critical self-reflection when interacting with people of cultural differences. It differs from the more well-known concept of cultural competence in that cultural humility is not culture specific and reflects provider attitudes and an orientation towards recognizing differences rather than specific knowledge about another culture. As such, cultural humility may lend itself to improving the care process across diverse patient populations. The literature on cultural humility and its relationship with CHWs is …

The Association Between Assorted Hormonal Contraceptive Methods And Advanced-Stage Epithelial Ovarian Cancer: A Systematic Review, Cheng Cheng

Dissertations and Theses (Open Access)

Epithelial ovarian cancer, the most lethal of the gynecological cancers, is typically diagnosed at advanced stages. Women diagnosed with advance-staged (i.e., stage III and IV according to the International Federation of Gynecology and Obstetrics) epithelial ovarian cancer are more likely to have recurrent episodes within 18 months17. According to a 2012 2016 case analysis conducted by the surveillance, epidemiology, and end results, or SEER program, the incidence of ovarian cancer was 11.4 per 100,000 women in all races per year with the highest incidence in non-Hispanic whites, of 11.9 per 100,000 women and the lowest incidence in Asians / Pacific …

Depression, Anxiety, And Social Anxiety As Predictors Of Help – Seeking Behavior Among U.S. University Students, Priya B. Thomas

Dissertations and Theses (Open Access)

Depression and anxiety are the top two mental health issues frequently cited by university students. Furthermore, the majority of students fail to seek professional help and may not find treatment useful. Many studies do not address the multiple factors that inhibit help seeking behaviors. This study aims to examine the associations between mental health issues and specific sociodemographic factors that may predict which students find seeking mental health treatment useful and are likely to seek help for their mental health issues over two semesters. Data from this study can be used to help develop strategies that help students maximize the …

Using S-Predixcan To Identify Associations Of Genetically Determined Gene Expression Levels With Carotid Intima Media Thickness, Andy Bryan A Castaneda

Dissertations and Theses (Open Access)

The aim of the study was to identify associations between predicted gene expression levels using S-PrediXcan and carotid intima media thickness (cIMT) in order to elucidate the etiology of atherosclerosis. Further, we wanted to compare our results to those from a transcriptome wide association study (TWAS) that used actual gene expression levels in whole blood. For our analysis we used summary statistics from a GWAS of cIMT from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, tissue-specific gene expression profiles from the GTEx project, and S-PrediXcan prediction models. The TWAS of cIMT that we compared our …

Treatment Outcomes Associated With Implementation Of An Express Sti Testing Model In A Prep Clinic In Austin, Texas, Diane Chau

Dissertations and Theses (Open Access)

It is unknown whether express STI testing is as effective as comprehensive STI testing. The research aims of this study are: (1) to describe the patients who obtained a STI testing at the Kind Clinic between February 01, 2019 to January 31, 2020; (2) to determine the association between STI testing type and sociodemographic factors, clinically-relevant factors, and treatment outcomes; (3) to visualize time-to-treatment among STI type and testing types for comparison on a diagnosis-level and a patient-level. Electronic medical records were abstracted for 2,201 patients that received an STI test during February 01, 2019 and January 31, 2020 at …

Exploration Of Breastfeeding As A Protective Factor For Breast Cancer In South African Women: A Nested Case-Control Study, Quiera S. Booker

Dissertations and Theses (Open Access)

South African’s (SA) breast cancer incidence rate is continually increasing (39 per 100,000 (2012) versus 46.2 per 100,000 (2018) with trends towards later-stage diagnosis. In previous literature, breastfeeding has been assessed as a protective factor for breast cancer; however, the SA population experiences inconsistent breastfeeding trends, rates, and support services. Therefore, this study will evaluate the inverse association between breast cancer and breastfeeding history. Methods. Cases (breast cancer) and controls (mastalgia) were matched 1:1 on clinical visit from May-August 2019 at Groote Schuur Hospital (GSH) in Cape Town, Western Cape, South Africa. Breastfeeding history, breast carcinoma diagnosis, and clinically relevant …

Raft-Versus-Host Disease Occurrence Among Cord Blood Transplantation Recipients In Relation To Human Leukocyte Antigen Match Grade, Sarah Chowdhury

Dissertations and Theses (Open Access)

Umbilical cord blood (UCB) transplantation has been consistently found to have low rates of graft-versus-host disease (GVHD), high rates of engraftment, and faster turnaround times in terms of finding suitable donors. In addition, it serves as a viable option for individuals with no matched donor options especially due to its flexible human leukocyte antigen matching criteria. Despite its advantages, there has been an overall decrease in UCB transplantation. However, its advantages emphasize the need for further research and investment in resources such as cord blood banking especially since pediatric populations are most likely to benefit from continued research due to …

Statistical Evaluation Of An Extension Of Linear Discriminant Analysis In Multiclass Settings With An Application For Detection Of Cervical Neoplasia, Frances A. Brito

Dissertations and Theses (Open Access)

Although a pathologists’ review of Papanicolaou smear cell samples has been successful in decreasing cervical cancer incidence, it is often costly and time-consuming. Quantitative cytology is a promising semi-automated method that measures cell features for further analysis or classification. There have been several advancements in classification algorithms, but many do not account for the nested data structure seen in quantitative cytology. Further, histologic diagnoses are separated into five or more classes, yet, multiclass classification has not been investigated. Here, we compare the predictive performance of macrolevel discriminant analysis (MDA) to traditional discriminant analysis methods in multi-class settings on cervical quantitative …

The Health And Wellness Characteristics Of Food And Beverage Service Industry Workers In Austin, Texas: A Participatory Cross-Sectional Survey, Alexandria Abbott

Dissertations and Theses (Open Access)

Food and beverage service industry workers are prone to tobacco use, alcohol abuse, illicit drug use, and mental health conditions. These workers are also highly likely to not have health insurance. Despite the poor health outcomes that stem from these conditions, little to no empirical evidence currently exists to explain the factors that contribute to the poor health condition of the service industry workforce. This study used a cross-sectional online survey to gather preliminary information on the health and wellness condition of service industry workers over the age of 18 in Austin, Texas. Survey respondents revealed high rates of alcohol …

Follow Up Care, Cancer Treatment Summaries And Patient Centered Communication, Ashleigh Gil

Dissertations and Theses (Open Access)

The adolescent and young adult (AYA) age group is the cohort of individuals who have been diagnosed with and/or are survivors of cancer. It is recommended they receive lifelong follow up care to prevent or mitigate late health effects associated with cancer and treatment. However, AYAs are caught between the pediatric and adult healthcare systems and they may not be able to fully advocate for their healthcare needs. Some factors that may be associated with AYAs survivorship care are treatment summaries and where they receive follow up care. This study aimed to identify if receipt of a treatment summary and …

Implementation Of Genetic Carrier Screening In The Ob Population: Healthcare Cost Impact And Recommendation Adherence, Aranza Gonzalez Cendejas

Dissertations and Theses (Open Access)

Background. The recent increases in availability of and demand for genetic testing have been observed alongside concerns regarding the appropriate ordering of such tests by providers, and subsequent unnecessary costs to the healthcare system. Professional organizations, such as ACOG and ACMG, develop guidelines to aid providers in ordering appropriate genetic testing. In this study, the ordering of carrier screening by obstetricians and genetic counselors was used to determine if duplicate genetic testing was taking place at a large academic institution along with adherence to ACOG and ACMG carrier screening guidelines.

Methods. A retrospective chart review of primigravida and multigravida women …

Alternative Carbon Utilization As A Virulence Determinant For Candida Albicans, Robert Williams

Dissertations and Theses (Open Access)

Candida albicans is a polymorphic unicellular fungus that has evolved to proficiently colonize and infect mammals. A common constituent of the microbiome in the GI tract, mouth, vagina, and skin, C. albicans is also an opportunistic pathogen capable of causing a variety of mucosal infections and the life-threatening disseminated candidiasis. Systemic C. albicans infections are a serious and growing issue; the fungus is the fourth most common cause of nosocomial bloodstream infections which has a mortality rate reaching 50%. As antifungal resistance continues to rise, it is critical that I understand the molecular basis of disseminated fungal infections.

The phagocytes …

Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share …

Vestigial-Like 1 Is A Shared Targetable Cancer-Placenta Antigen Expressed By Pancreatic And Basal-Like Breast Cancers, Sherille Denae Bradley

Dissertations and Theses (Open Access)

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regression by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from tumors of PDAC patients. This led to the identification of a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1), a novel putative TAA demonstrating overexpression in multiple tumor types and low or absent transcript expression in normal tissues with the exception of placenta. VGLL1-specific CTL isolated and expanded from the blood of a male PDAC patient …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations and Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan

Dissertations and Theses (Open Access)

Antibiotic resistance is a major global public health threat. Enterococci are recalcitrant, nosocomial pathogens that can be intrinsically resistant to valuable antibiotics, like beta-lactams, or evolve resistance to all existing antimicrobials. The LiaFSR system regulates resistance to cell membrane (CM) stressors like daptomycin (DAP), a front-line drug for multi-drug resistant infections. DAP resistance (DAP-R) in E. faecalis is mediated by CM phospholipid alterations. Emergence of DAP-R often leads to b-lactam resensitization, a phenomenon called the seesaw effect. The molecular mechanism of DAP-R and the seesaw effect are unknown. Here we show that LiaX is a surface exposed protein whose C-terminal …

Hypothalamic Circuits Mediating Consumption And Anxiety, Ryan Cassidy

Dissertations and Theses (Open Access)

From 1960-2016, U.S. obesity prevalence increased 13-40% and diabetes increased from 3-15%. There is an epidemic of metabesity, the aggregate metabolic disorders produced by chronic overeating. Drugs for metabesity were developed in the 1930s with limited effectiveness; agents today rely on the same principles and are similarly ineffective. Particularly surprising has been the failure of satiety enhancers; this indicates it may not be that physiologic hunger drives chronic overeating. Although hunger and satiety affect traditional reward circuitry (Cassidy & Tong 2017), evidence for the primacy of this effect is mixed. Being hungry reduces anxiety-like behavior in mice; whether the …

Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu

Dissertations and Theses (Open Access)

High-throughput forward genetic screenings are invaluable tools to systematically explore genetic interactions and to link gene disruption with disease contexts. The adaptation of CRISPR/Cas9 has improved the sensitivity and specificity of functional screenings. Despite this advance, there remains a long-standing need to improve functional screenings with smaller and more versatile pooled libraries. Capitalizing on the inherent multiplexing capability of a class 2 CRISPR enzyme AsCpf1, we developed a multiplexed, high throughput screening strategy that has avoided the usual trade-off between library size and library penetration, allowing library minimization without sacrificing gene targeting efficiency. We optimized the AsCpf1 protein for functional …

Bayesian Adaptive Designs And Versatile Software Platform For Early Phase Clinical Trials, Yanhong Zhou

Dissertations and Theses (Open Access)

This research is dedicated to improve the efficiency of Bayesian adaptive designs for early phase clinical trials. Phase I clinical trials can be conducted using algorithm-based (also known as rule-based), model-based, or model-assisted designs. Numerous studies have shown that model-assisted designs have the simplicity of algorithm-based designs while possessing the great performance of the model-based designs. Despite the desirable properties of current model-assisted designs, their use is still limited. More importantly, they can fall short of tackling some emerging challenges brought by the development of novel therapies. Thus, there is a pressing need for model-assisted designs that can complement the …

Receptor Tyrosine Kinases-Mediated Acquired Parp Inhibitor Resistance In Breast Cancer, Mei-Kuang Chen

Dissertations and Theses (Open Access)

Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility genes (BRCA^m). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, I developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) cell …

Factors That Impact Uptake Of Carrier Screening By Male Reproductive Partners Of Female Prenatal Patients, Wendi Betting

Dissertations and Theses (Open Access)

Carrier screening is a genomic technology that is used to identify individuals who are carriers of autosomal recessive conditions. Despite published recommendations, the majority of male partners do not complete carrier screening after their female partner is identified to be a carrier. Previous studieshave examined reasons why women elect or decline carrier screening, but there have been few published studies that examine factors that influence a male partner’s decision to elect or decline carrier screening, particularly when the female has been identified as a carrier. The aim of the study was to determine the factors that influence the uptake of …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Assessing Patient Attitudes To Ward Genetic Testing For Hereditary Hematologic Malignancy, Addison Johnson

Dissertations and Theses (Open Access)

Since 2003, more than 15 genes have been identified to predispose to hereditary hematologic malignancy (HHM). Although the diagnostic yield of germline analysis for leukemia is similar to solid tumors, referral for genetic evaluation in adults with leukemia is underperformed. Identifying HHM is important for prognostication, treatment, and donor selection for hematopoietic stem cell transplant. No studies have examined leukemia patients’ attitudes toward genetic testing for HHM. This study aimed to assess leukemia patients’ attitudes toward genetic testing and elicit current perceived distress due to a leukemia diagnosis. Data were elicited through an electronic survey sent to 5,513 patients diagnosed …

Genetic Counselors' Approaches To Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer, Sarah Burke

Dissertations and Theses (Open Access)

Given the increasing availability of health-related direct-to-consumer genetic testing (DTC-GT) and third-party interpretation (TPI) services, it is likely that genetic counselors (GCs) will continue to encounter consumers that require follow-up counseling for their results. The National Comprehensive Cancer Network recommends clinical-grade genetic testing to confirm commercial results; however, the type of testing that GCs select remains uncharacterized. Therefore, we aimed to describe the specific recommendations that cancer GCs make for confirmatory genetic testing in probands who have already obtained DTC-GT results or TPI data that reported a BRCA1/2 pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered …

Modulation Of Pi3k-Akt Pathway In Colorectal Cancer, Maliha Nusrat

Dissertations and Theses (Open Access)

The phosphatidylinositol-3-kinase (PI3K) signaling pathway is activated in 20-40% colorectal cancers (CRC) through PTEN loss (PTEN^loss) and PIK3CA mutations (PIK3CA^mut). Allosteric AKT inhibition with MK2206 monotherapy has been ineffective in CRC patients. We investigated the impact of MK2206 on pharmacodynamic (PD) markers and signaling pathways using reverse phase protein array (RPPA) on (1) paired tumor biopsies from a clinical trial of MK2206 in PI3K-altered metastatic CRC, (2) PTEN^lossCRC patient derived xenografts (PDX) treated with MK2206 or carrier, and (3) MK2206-treated cell lines. PD inhibition was deep in cell lines, less but significant in …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations and Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help …