Digital Commons Network^™

Attitudes To Ward Updated Genetic Testing Among Patients With Unexplained Mismatch Repair Deficiency, Jessica Omark

Dissertations and Theses (Open Access)

Individuals who have colorectal cancer (CRC) or endometrial cancer (EC) displaying loss of immunohistochemical (IHC) staining of one or more mismatch repair (MMR) proteins without a causative germline mutation are said to have unexplained mismatch repair deficiency (UMMRD, also known as mutation-negative Lynch syndrome). Comprehensive genetic testing that could potentially further clarify Lynch syndrome (LS) carrier status is essential to provide tailored screening guidelines to affected individuals and their family members; however, patient understanding of the potential impact of updated genetic testing for LS is unclear. This study aimed to evaluate the interest in and perceived impact of updated genetic …

The Epithelial To Mesenchymal Transition In Breast Cancer Induces Alterations In Metabolism, Esmeralda Ramirez-Peña

Dissertations and Theses (Open Access)

Metastasis is currently incurable. Recent studies suggest that metabolic reprogramming significantly impacts metastatic progression. Understanding the underlying biology of how metabolic reprogramming influences metastasis will shed light on developing novel ways to treat metastasis and is of urgent clinical need. A potent mediator of metastatic potential in breast cancer is the winged helix/Forkhead domain transcription factor FOXC2. We have previously shown that FOXC2 is necessary and sufficient to promote metastasis through induction of the epithelial to mesenchymal transition (EMT). EMT is a latent embryonic program that is aberrantly induced in breast cancer cells conferring migratory and invasive capabilities in addition …

Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma, Pavitra Viswanath

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Outcomes are poor for patients with recurrent, advanced or metastatic NSCLC. Polo-like kinase 1 (PLK1), involved in the regulation of mitotic processes and the response to DNA damage, is overexpressed in NSCLC. Inhibiting PLK1 may be an effective treatment for NSCLC patients as it is involved in the mechanisms of resistance to several chemotherapy drugs. PLK1 inhibition or knock-down has various effects in cancer cells, including mitotic arrest, apoptosis, and senescence. Predictive biomarkers have not been identified to select those patients who are likely to respond to …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations and Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Identification Of Tissue And Circulating Biomarkers For Premalignant And Malignant Lesions, Shu-Hong Lin

Dissertations and Theses (Open Access)

Recent advancement in technologies including next-generation sequencing and production-scale throughput qPCR have revolutionized the identification of biomarkers in the epidemiology field. In response to the vast amount of data generated from high-throughput technologies, novel inventions in the computer sciences fields have been applied to analyze these data. The current study demonstrates the application of such technologies in a variety of scenarios.

I first described how targeted and whole-exome sequencing were used to identify somatic mutations which marked the differences between colorectal adenomas and adenocarcinomas. A statistical test based on the unique clustering pattern of tumor suppressor genes and oncogenes was …

Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu

Dissertations and Theses (Open Access)

Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer, Sunil Acharya

Dissertations and Theses (Open Access)

Distant metastasis is the primary cause of breast cancer–related mortality. To date, effective therapeutic drugs that target metastasis are still lacking. Triple negative breast cancer (TNBC) occurs in high frequency in young women and are more likely to recur and metastasize than are other breast cancer subtypes. Also, TNBC patients cannot benefit from currently available hormonal or targeted therapies, as they lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Thus, understanding the signaling pathways that promote TNBC metastasis and developing novel therapeutic approaches to target them are critical, in order to prolong the survival and improve …

Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui

Dissertations and Theses (Open Access)

p63 is a member of the p53 family, a well-known tumor suppressor which is considered the guardian of the genome. The TP63 gene encodes multiple isoforms that can be categorized into two main isoforms, TAp63 and ΔNp63, which are expressed in different cellular compartments and have distinct functions in many biological processes. While the Flores laboratory identified TAp63 as a tumor and metastasis suppressor, the precise roles of ΔNp63 isoforms in tumorigenesis and metastasis remain elusive. ΔNp63 is the predominant p63 isoform expressed in the epidermis and plays essential roles in regulating epidermal development and homeostasis. Utilizing a ΔNp63-conditional …

Bayesian Designs For Early Phase Clinical Trials With Novel Target Agents, Heng Zhou

Dissertations and Theses (Open Access)

My dissertation mainly focus on Bayesian designs for early phase clinical trials with novel target agents. It includes three specific topics: (1) reviewing novel phase I clinical trial designs and comparing their operating characteristics; (2) Proposing a Bayesian optimal phase II clinical trial (BOP2) design with simple and complex endpoints under a unified framework; and (3) extending the BOP2 design to incorporate the durable clinical response as a primary endpoint.

A number of novel model-based and model-assisted designs have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and …

Identifying Molecular Targets And Validating Novel Therapies For Ovarian Cancer, Alejandro Villar-Prados

Dissertations and Theses (Open Access)

Re-purposing of targeted therapies for additional tumor types is a promising avenue for expanding treatment options for cancer patients, however accurately predicting what re-purposed targeted therapy will be effective remains challenging. To address this need, we developed a Therapy Predicting Tool (TPT) that accurately predicts the beneficial therapeutic effect of clinically relevant targeted therapies and the downstream pathways they may impact in the cancer of interest. Using ovarian cancer as a model to biologically validate our tool, we determined that Bromodomain and Extra-Terminal motif inhibitors (BETis), which target proteins such as BRD4, held the greatest promise to produce therapeutic effects …

Identification And Utility Of Dna In Exosomes, Paul Kurywchak

Dissertations and Theses (Open Access)

Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease. …

Uncertainty In Illness And Health Literacy In Pancreatic Cancer Patients, Rae Reynolds

Dissertations and Theses (Open Access)

Background: Despite a shared link to cognitive processing of health information suggested by their definitions, information on the association between uncertainty and health literacy is scarce. Their relationship has not been studied in pancreatic cancer patients.

Aims: To evaluate uncertainty and health literacy in pancreatic cancer patients, examine their bivariate correlation, and determine significant predictors.

Methods: This descriptive, cross-sectional study was conducted in a comprehensive cancer center. Uncertainty was measured using the Mishel Uncertainty in Illness Scale -Community and health literacy was measured using the Cancer Health Literacy Test 30. Spearman’s rho tested correlation and linear regression models were …

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Faculty, Staff and Student Publications

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased …

Public Hospitals Matter, Herbert L Fred

The Texas Heart Institute Journal

Recent events in this country pose major concerns. Police shoot unarmed blacks, gun-wielding malcontents ambush policemen, white supremacists march, gays are murdered, gender inequality pervades our workforce, and sexual harassment and abuse are surfacing in many segments of our society. In reaction, various social movements have sprung up, including Black Lives Matter, White Lives Matter, Blue Lives (policemen) Matter, Gay Lives Matter, Girls for Gender Equity (GGE), #MeToo, and Time's Up. To that list, I add another battle cry: Public Hospitals Matter.

Meta-Analysis Of The Effects Of Exercise Interventions On Obese Adolescents, Brandy E. Strahan Phd, Rn, Hyochol Ahn Phd, Ms-Ece, Ms-Cts, Aprn, Anp-Bc, Jonathan Shuster M.Sc., Ph.D.

Journal of Nursing & Interprofessional Leadership in Quality & Safety

A meta-analysis of 10 randomized control studies published in 2003-2013 was conducted to provide a summary of the effects of exercise interventions on obese adolescents. Outcomes of the reviewed trials included body mass index, weight, glucose, and triglycerides. Data were combined using an inverse variance weighted random effects model. The effect size estimate for BMI was 1.354 kg/m² (p < 0.001, SE 0.321), indicating that the BMI of individuals in treatment groups improved, as compared to control groups. A statistically significant reduction in weight was greater in the intervention groups than the control groups by 3.815 kg (p = 0.001, SE 1.101). The findings of this meta-analysis show that exercise interventions may improve control of weight and BMI and in turn be a factor in decreasing obesity.

Sexting And Mental Health: A School-Based Longitudinal Study Among Youth In Texas, Pooja Chaudhary, Melissa Peskin, Jeff R. Temple, Robert C. Addy, Elizabeth Baumler, Ross Shegog

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: Sexting has emerged as a common socio-cultural problem in our society today. Few studies have estimated the prevalence of sexting among younger middle school youth and even fewer have assessed the relationship between sexting and mental health outcomes like anxiety and depression symptoms among middle school youth.

Objectives: To estimate the prevalence of sexting among sixth and seventh-grade middle school students in a large urban school district in Southeast Texas and to assess its relationship with mental health outcomes (both anxiety and depression) among these youth.

Methods: A retrospective analysis of an existing three-year randomized, two-arm, nested longitudinal study …

Special Issue Introduction: Youth At Risk, Melisa Creamer, Anna Wilkinson, Deanna Hoelscher, Steven Kelder

Journal of Applied Research on Children: Informing Policy for Children at Risk

Guest editors MeLisa Creamer, Anna Wilkinson, Deanna Hoelscher and Steven Kelder introduce Volume 8, Issue 2 of the Journal of Applied Research on Children.

Marijuana And E-Cigarette Use In A Us National Sample Of 8th And 10th Grade Never-Smokers Of Conventional Cigarettes, Olusegun Owotomo, Julie Maslowsky

Journal of Applied Research on Children: Informing Policy for Children at Risk

Introduction: E-cigarette use remains a controversial topic in public health and medicine. Historically, cigarette smoking was identified as a gateway to marijuana use among adolescents. Recently, the prevalence of adolescent cigarette smoking has declined, but that of e-cigarette use continues to increase. As e-cigarettes eclipse cigarettes among adolescents, e-cigarette use may predispose adolescents to marijuana use. This study examines the relationship between e-cigarette use and marijuana use in a national sample of adolescents who have never smoked conventional cigarettes.

Methods: A national sample of 8th and 10th grade never-smokers of conventional cigarettes (N=12,743) was obtained from 2014-2015 Monitoring …

Adolescent Marijuana Use And Co-Occurrence With Tobacco Use: Implications For Tobacco Regulation, Erika Trapl, Sarah J. Koopman Gonzalez

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: Marijuana use among high school youth has been declining over the past two decades. However, there has been a notable shift in the national landscape with regards to social norms and marijuana legalization that could allow marijuana to become more available and may compete against prevention efforts among youth. Further, youth continue to utilize innovative ways to consume marijuana. There is a documented relationship between marijuana and tobacco use, particularly with the use of blunts. Despite the documented relationship between tobacco and marijuana use, little is known about the modes of marijuana use in relation to different tobacco products. …

Does Exposure And Receptivity To E-Cigarette Advertisements Relate To E-Cigarette And Conventional Cigarette Use Behaviors Among Youth? Results From Wave 1 Of The Population Assessment Of Tobacco And Health Study, Nicole E. Nicksic Phd, Mph, L. Morgan Snell Mpp, Andrew J. Barnes Phd

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: E-cigarettes (EC) are the most commonly used tobacco product among youth. Additionally, youth EC users are progressing to smoking conventional cigarettes (CC). Although known to target youth, there are no current restrictions in the US on EC marketing, including advertising. The purpose of this study is to evaluate the relationship between EC advertisements and youth EC and CC use behaviors.

Methods: This study analyzed data from youth (12-17 years) aware of EC in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) study (n=12,199). Weighted logistic regression models assessed whether exposure and receptivity to any of …

“If You Are Old Enough To Die For Your Country, You Should Be Able To Get A Pinch Of Snuff”: Views Of Tobacco 21 Among Appalachian Youth, Lindsay K. Tompkins, Clara G. Sears, Joy L. Hart, Kandi L. Walker, Alexander S. Lee, Aruni Bhatnagar

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: Multiple strategies have been utilized in attempts to decrease the prevalence of youth tobacco use. One strategy, raising the minimum legal sale age (MLSA) of tobacco products to 21, known as Tobacco 21, has recently gained popularity. Tobacco 21 legislation targets youth tobacco use by obstructing two main sources of youth tobacco products: stores and older friends. Although these sources are the most common for youth across the nation, regional differences have not been explored. Further, youth perspectives about raising the tobacco MLSA have not been considered. Youth may help identify potential challenges to implementing tobacco control measures, as …

A Comparison Of Sociodemographic Correlates Of Cigarette, Alcohol, And Energy Drink Consumption Among High School Students In The United States, 2010-2015, Eun Me Cha, Nalini Ranjit, Deanna M. Hoelscher

Journal of Applied Research on Children: Informing Policy for Children at Risk

OBJECTIVE: Despite growing awareness about the harmful physiological effects of energy drinks, especially among young people, there is little regulation governing the marketing and sale of these products to adolescents. Thus, in contrast to substances such as cigarettes and alcohol, energy drinks are readily available to adolescents, and widely consumed. It is not known if the easy availability of energy drinks has the effect of increasing usage of these substances among adolescents, and reducing sociodemographic differences in the consumption of energy drinks. In this study, we use pooled data (2010-2015) from the nationally representative Monitoring the Future survey (n=43,283), to …

Annual Report 2017 - 2018, Houston Academy Of Medicine - Texas Medical Center Library

Annual Reports: 1943 - Present

This file contains the Annual Report for the library from 2017-2018.

Ms225: 2018 Faculty Meeting Minutes, Thomas R. Cole

Thomas R. Cole, PhD Papers

Original Filename: Faculty Meeting Minutes 020718 SWOT_SACRED VOCATION PROGRAM.docx. Format Details: fmt/412; Microsoft Word for Windows; 2007 onwards. See more at Thomas R. Cole, PhD Papers and its finding aid.

Clinical Utility Of The Dsm-5 Alternative Model For Borderline Personality Disorder: Differential Diagnostic Accuracy Of The Bfi, Scid-Ii-Pq, And Pid-5, J Christopher Fowler, Alok Madan, Jon G Allen, Michelle Patriquin, Carla Sharp, John M Oldham, B Christopher Frueh

Staff and Researcher Publications

Background: With the publication of DSM 5 alternative model for personality disorders it is critical to assess the components of the model against evidence-based models such as the five factor model and the DSM-IV-TR categorical model. This study explored the relative clinical utility of these models in screening for borderline personality disorder (BPD).

Methods: Receiver operator characteristics and diagnostic efficiency statistics were calculated for three personality measures to ascertain the relative diagnostic efficiency of each measure. A total of 1653 adult inpatients at a specialist psychiatric hospital completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews, SCID-II Questionnaire (SCID-II-PQ) …

Characterizing The Information Needs Of Rural Healthcare Practitioners With Language Agnostic Automated Text Analysis, Melissa Resnick

Dissertations and Theses (Open Access)

Objectives – Previous research has characterized urban healthcare providers' information needs, using various qualitative methods. However, little is known about the needs of rural primary care practitioners in Brazil. Communication exchanged during tele-consultations presents a unique data source for the study of these information needs. In this study, I characterize rural healthcare providers' information needs expressed electronically, using automated methods.

Methods – I applied automated methods to categorize messages obtained from the telehealth system from two regions in Brazil. A subset of these messages, annotated with top-level categories in the DeCS terminology (the regional equivalent of MeSH), was used to …

Using The Literature To Identify Confounders, Scott Malec

Dissertations and Theses (Open Access)

Prior work in causal modeling has focused primarily on learning graph structures and parameters to model data generating processes from observational or experimental data, while the focus of the literature-based discovery paradigm was to identify novel therapeutic hypotheses in publicly available knowledge. The critical contribution of this dissertation is to refashion the literature-based discovery paradigm as a means to populate causal models with relevant covariates to abet causal inference. In particular, this dissertation describes a generalizable framework for mapping from causal propositions in the literature to subgraphs populated by instantiated variables that reflect observational data. The observational data are those …

Vitamin E Status Is Inversely Associated With Risk Of Incident Tuberculosis Disease Among Household Contacts, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have previously assessed how pre-existing vitamin E status is associated with risk of tuberculosis (TB) disease progression.

OBJECTIVE: We evaluated the association between baseline plasma concentrations of 3 vitamin E isomers (α-tocopherol, γ-tocopherol, and δ-tocopherol) and TB disease risk.

METHODS: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima, Peru. We defined cases as HHCs who developed active TB disease ≥15 d after the diagnosis of the index patient, and we matched each case to 4 control cases who did not develop active TB based on …