Digital Commons Network^™

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 …

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 …

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 …

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 …

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 …

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 …

Frequency Of Copy Number Variants Involving The Sex Chromosomes In A Clinical Setting, Autumn Vara

Dissertations and Theses (Open Access)

Copy number variants (CNVs) are a common finding in the clinical setting and contribute to both genetic variation as well as disease. Recently, studies have described the accumulation of multiple CNVs as a disease modifying mechanism. While it has been characterized how additional CNVs may play a role in phenotype, in which ways and to what extent sex chromosomes are involved has not been fully described. We performed a secondary data analysis using the DECIPHER database on 2,273 de-identified individuals with 2 CNVs. CNVs were designated primary and secondary based on our criteria and characteristics of both CNV groups were …

Genetic Counselors' Experiences With And Approaches To Discordant Genotypic And Phenotypic Sex Detected Via Non-Invasive Prenatal Testing, Emily Stiglich

Dissertations and Theses (Open Access)

As the use of non-invasive prenatal testing becomes more ubiquitous during pregnancy, genetic counselors (GCs) will see clients more frequently for discordant sex identification via non-invasive prenatal testing (NIPT-DSI). Thus, it is imperative to investigate what GCs consider important when counseling about NIPT-DSI and assess how GCs perceive their role in such cases. Prenatal and pediatric GCs were surveyed regarding previous experiences of NIPT-DSI, comfort levels of topics relating to NIPT-DSI, and perceived importance of potential discussion topics in a counseling session (n = 108). The survey consisted of two vignettes, presenting cases of NIPT-DSI identified prenatally in one …

Understanding Intercellular Signaling During Lung Injury-Repair, Margo Patricia Cain

Dissertations and Theses (Open Access)

The mammalian lung is a complex system of specialized cell types with precise spatial organization designed to cooperate to perform gas exchange. These cell types together coordinate organ development, homeostasis, and repair after injury through signals either presented or secreted, known as ligands, to be received by receptors on the surface of another, or in some cases, the same cell. The alveolar region of the lung, the primary region of gas exchange, responds to various types of injuries with different lung repair mechanisms. In order to explore how the various cell types in the lung communicate to drive tissue repair …

Vasopressor Treatment And Mortality Following Nontraumatic Subarachnoid Hemorrhage: A Nationwide Electronic Health Record Analysis, George Williams, Vahed Maroufy, Laila Rasmy, Derek Brown, Duo Yu, Hai Zhu, Yashar Talebi, Xueying Wang, Emy Thomas, Gen Zhu, Ashraf Yaseen, Hongyu Miao, Luis Leon Novelo, Degui Zhi, Stacia M Desantis, Hongjian Zhu, Jose-Miguel Yamal, David Aguilar, Hulin Wu

Faculty, Staff and Student Publications

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH.

METHODS: The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH …

Structure And Mechanism Of Human Diacylglycerol O-Acyltransferase 1, Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Diacylglycerol O-acyltransferase-1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the superfamily of membrane-bound O-acyltransferases (MBOAT) that are found in all kingdoms of life and involved in acylation of lipids and proteins2,3. It remains unclear how human DGAT1 (hDGAT1) or other mammalian members of the MBOAT family recognize their substrates and catalyze their reactions. The absence of three-dimensional structures also hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A solved …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose …

Efficacy Of Quality Improvement And Patient Safety Workshops For Students: A Pilot Study, Kevin P Shah, Shreya Goyal, Vignesh Ramachandran, Jaden R Kohn, Jonathan A Go, Zachary Wiley, Anoosha Moturu, Meera K Namireddy, Anjali Kumar, Ryan C Jacobs, Matthew Stampfl, Jesal R Shah, Justin Fu, Weijie V Lin, Brandon Ho, Grace Wey, Sophie Y Lin, Andrew C Caruso, Lindsey Jordan Gay, Diana E Stewart, Sara Andrabi

Faculty, Staff and Students Publications

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes.

METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Modulating The Rate Of Fibrin Formation And Clot Structure Attenuates Microvascular Thrombosis In Systemic Inflammation, Christian Valladolid, Marina Martinez-Vargas, Nitin Sekhar, Fong Lam, Cameron Brown, Timothy Palzkill, Alexander Tischer, Mathew Auton, K Vinod Vijayan, Rolando E Rumbaut, Trung C Nguyen, Miguel A Cruz

Faculty, Staff and Students Publications

Systemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in …

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …