Digital Commons Network^™

Cholesterol Efflux Capacity And Its Association With Metabolic Syndrome In A Multi-Ethnic Population (Dallas Heart Study): A Cross-Sectional Study, Oludamilola Akinmolayemi

Dissertations and Theses (Open Access)

Metabolic syndrome (MetS) is a multi-component risk factor for cardiovascular disease (CVD) and type 2 diabetes. MetS has been found to be associated with increased risk of incident CVD, cardiovascular morbidity and mortality, and prevalence atherosclerosis. Cholesterol efflux capacity (CEC) is a measure of the functional property of high-density lipoprotein cholesterol (HDL-C). In addition, it characterizes the ability of HDL-C to accept cholesterol from extra-hepatic cells in the periphery to the liver and has been shown in clinical studies to be inversely associated with atherosclerosis cardiovascular disease (ASCVD) and incident cardiovascular disease (CVD) . Low HDL-C is one of the …

Insuring The Integrity Of Global Registries, Aardhra Meenakshi Venkatachalam

Dissertations and Theses (Open Access)

Data quality is a priority in public health because it is used for public health program planning and implementation, research, as well as policy. The information gleaned from the data allows us to assess health status, and improve health needs. This paper evaluated methods for cleaning, managing and addressing missing data in the Lagos State Ambulance Service registry. The techniques included screening, data organization, diagnostic phase, treatment phase and a missing data phase to holistically handle the data. The percentage of systemic errors was reduced through the use of the 5-step method. Missing data was informative for state of origin, …

Vasopressor Titration In Medical Intensive Care Patients With Septic Shock: A Descriptive Study, Daniel Arellano

Dissertations and Theses (Open Access)

Background: Vasopressor therapy in patients with septic shock can lead to harmful effects.

Objective: To describe vasopressor titration in patients with septic shock.

Methods: Single-center descriptive study of 60 intensive care unit (ICU) patients to calculate rates for events of failure to titrate, incorrect titration, and correct titration in 15- minute intervals for the duration of vasopressor therapy. Total hospital and ICU days, mortality rate, vasopressor dose and time, and the impact of hydrocortisone on vasopressor use were examined.

Results: During the total vasopressor infusion time of 2598 hours, 5395 failure-to-titrate events were noted. There were 316 incorrect titrations and …

Characterizing Risk & Burden Of Lower Cranial Neuropathy (Lcnp) As Late Effect Among Oropharyngeal Cancer Survivors, Puja Aggarwal

Dissertations and Theses (Open Access)

Background: Lower cranial neuropathy (LCNP) is a rare but potentially disabling late effect of radiotherapy (RT) and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment with deficits in swallowing, speech, and voice. The aims of this research were: 1) to quantify the cumulative incidence of late LCNP and identify clinical predictors of late LCNP; 2) to investigate the impact of late LCNP on severity of cancer treatment-related symptoms, general functional impairment (GFI), and single item scores of the most severe symptoms; and 3) to quantify the association of late LCNP with swallowing-related …

Association Between Childhood Maltreatment And Type 2 Diabetes Mellitus: A Retrospective Cohort Study In The United States, Diep N. Poulos

Dissertations and Theses (Open Access)

This retrospective cohort study analyzed self-reported and biological data collected from MIDUS in 2004-2006 to understand the association between the types of childhood maltreatment (CM) and Type 2 Diabetes Mellitus (T2DM). The central hypothesis of this study is that childhood maltreatment is positively associated with adult onset diabetes (T2DM). CM has been associated with lifelong morbidity and an increased risk in chronic diseases such as diabetes and heart disease (Bernstein RE, 2013). In this study, CM was defined by the Childhood Trauma Questionnaire (CTQ). The CTQ has three types of abuse: physical, sexual, emotional, and two types of neglect: physical …

The Potential Impact Of Restricting The Sale Of Tobacco At Tobacco Retail Outlets Surrounding Schools Across Major Metropolitan Areas Of Texas On Tobacco Advertisements, Udoka C. Obinwa

Dissertations and Theses (Open Access)

Retail outlets that sell tobacco (ROST) are the leading channel of advertisements and promotional efforts for tobacco companies. Tobacco companies strategically target youth, young adults, racial and ethnic minorities and individuals in lower SES areas with more advertisements, which in turn influences their tobacco use behavior. Researchers have proposed instituting place-based restriction strategies as a way to control tobacco use. This dissertation examined the potential impact of i) restricting the sale of tobacco at ROST within 1000ft of schools and 2000ft of colleges and ii) restricting the sale of tobacco at ROST within 500ft of other ROST, on the number …

Clinical And Demographic Factors Associated With Peg-Asparaginase-Related Toxicities In Patients With Acute Lymphoblastic Leukemia, Priyadarshani Dharia

Dissertations and Theses (Open Access)

Introduction: Polyethylene glycol (PEG)-asparaginase is one of the first-line drugs in pediatric ALL treatment. Although a complete and prolonged treatment with PEGasparaginase has been instrumental in improving the survival of ALL patients, it is associated with four common toxicities: hypersensitivity, hyperbilirubinemia, pancreatitis, and venous thromboembolism (VTE). PEG-asparaginase-related toxicities may require modifications and delays in treatment, which often leads to poor treatment outcomes. Previous studies of PEG-asparaginase-related toxicities have mainly focused on individual toxicities. Further, these studies were conducted in study populations which were predominantly self-reported non-Hispanic whites. Therefore, there is a gap in the knowledge regarding the cumulative burden of …

Characterizing Risk & Burden Of Lower Cranial Neuropathy (Lcnp) As Late Effect Among Oropharyngeal Cancer Survivors, Puja Aggarwal

Dissertations and Theses (Open Access)

Background: Lower cranial neuropathy (LCNP) is a rare but potentially disabling late effect of radiotherapy (RT) and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment with deficits in swallowing, speech, and voice. The aims of this research were: 1) to quantify the cumulative incidence of late LCNP and identify clinical predictors of late LCNP; 2) to investigate the impact of late LCNP on severity of cancer treatment-related symptoms, general functional impairment (GFI), and single item scores of the most severe symptoms; and 3) to quantify the association of late LCNP with swallowing-related …

Moving Beyond The Single Gene: Integrative Gene Set Analysis For Rna-Seq, Andrew Richard Aschenbrenner

Dissertations and Theses (Open Access)

RNA-seq is the next-generation sequencing technology for gene expression and while many tools have been developed to assess differential expression, most focus on gene-level statistics. Gene-level statistics implicitly ignore any dependence among genes. In order to directly incorporate correlation into testing for differential expression, genes are sorted into networks using Ingenuity Pathway Analysis (IPA) and the gene expression of each network is modeled using Generalized Estimating Equations (GEE). Since the gene network data often exhibits correlation structures containing positive and negative values, a new intermediate correlation structure is developed. This structure provides a compromise between an exchangeable (one parameter for …

The Associations Between Fat And Clinical Outcomes Among Lung Cancer Patients: Dietary Intake And Genetic Determinants, Fang Yu Lin

Dissertations and Theses (Open Access)

Higher dietary fat intake and alterations in fatty acid metabolism may affect cancer development and progression. This dissertation conducted a series of studies examining whether dietary fat intake and genetic variants in fatty acid metabolism genes have an impact on clinical outcomes among non-Hispanic whites newly diagnosed with non-small cell lung cancer (NSCLC). First, a cohort of 2,262 NSCLC patients was prospectively examined for intakes of total, saturated, monounsaturated, and polyunsaturated fat in relation to overall survival and recurrence. Dietary fat intake at diagnosis was assessed with a previously validated food frequency questionnaire and categorized by Dietary Reference Intakes. Multivariable …

Examining Differences In Physical Activity By Socio-Demographics, Employment, And Social Support Among U.S. Adolescents, Ashleigh Marie Johnson

Dissertations and Theses (Open Access)

The overall decline in physical activity levels during adolescence supports the examination of intrapersonal-, interpersonal-, and behavior-level factors that may influence physical activity behavior among this population. The three papers within this dissertation aimed to examine associations of socio-demographics and socio-environmental factors with physical activity among U.S. adolescents. Papers 1 and 3 used data from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Paper 1 examined differences in adolescent physical activity by gender and race/ethnicity, and examined modification by grade and socioeconomic status (SES). Paper 3 examined the association of parent- and adolescent-reported parental social support with adolescent …

Understanding The Relatlonships Between Survivorship Care Plans And Survivor Level Outcomes Among Breast And Colorectal Cancer Survivors, Jessica Danielle Austin

Dissertations and Theses (Open Access)

PURPOSE: Cancer survivors have complex journeys following the completion of active treatment. The Institute of Medicine and other high-profile organizations have recommended and mandated the use of a survivorship care plan (SCP) despite mixed evidence supporting the impact of SCPs on key survivor-level outcomes. The purpose of this dissertation was to understand the complex relationship linking the delivery of SCPs and to relevant survivorlevel outcomes. STUDY GROUP: This dissertation focuses on breast and colorectal cancer survivors because they comprise nearly 30% of the entire cancer survivor population in the US and are the two most prevalent cancers in men and …

The Role Of Gamma Oscillations And Cortical Inhibition In The Development Of Working Memory In Adolescence, Christopher P. Walker

Dissertations and Theses (Open Access)

Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations and Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations and Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

A Signature Enrichment Design With Bayesian Adaptive Randomization For Cancer Clinical Trials, Fang Xia

Dissertations and Theses (Open Access)

Clinical trials in the era of precision medicine demand more flexible and efficient trial designs. Adaptive clinical trial designs allow pre-specified modifications of an on-going clinical trial and could shorten the trial duration. We reviewed five common types of adaptive clinical trials based on adaptation methods. In particular, outcome-randomization becomes more popular as it can assign more patients to the promising treatments based on the accumulated trial data. This data-driven allocation allows more patients to benefit from the trial, which is especially important for cancer patients. We compared different Bayesian outcome-adaptive randomization methods and discussed them from both methodological and …

Assessment Of New Innovations In Pet/Ct For Respiratory Motion Correction, Joseph Meier

Dissertations and Theses (Open Access)

In oncological imaging, Positron Emission Tomography/Computed Tomography (PET/CT) is a vital tool used for stating and treatment response assessment of patients due to its ability to visualize and accurately quantify the bio-distribution of radiolabeled pharmaceuticals. However, due to the long acquisition times, respiratory motion blur is unavoidable in PET images especially in the lower lung and upper abdomen. This leads to reductions in measured radiotracer concentration and lesion detectability all of which can potentially result in incorrect management of patients. Multiple methods exist to correct for respiratory motion but are rarely used in the routine clinical setting because of: 1) …

Deconvolute Brain Tumor Genomic Alterations Based On Dna Methylation, Jie Yang

Dissertations and Theses (Open Access)

Molecular classification based on mutations, expression subtypes, and copy number variants has improved diagnosis and treatment decision-making for patients with brain tumors, particularly malignant gliomas. However, the association between epigenetic signature and genetic alterations is poorly understood. For example, mutation of isocitrate dehydrogenase (IDH) is associated with genome-wide hypermethylation of CpG islands in gliomas. But other subtype-associated alterations, including telomerase reverse transcriptase (TERT) promoter mutation, alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation, chromosome 1p19q co-deletion (chr1p19q codel), and gene expression subtypes, have yet to be associated with any epigenetic signature. Therefore, we hypothesized that …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations and Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch

Faculty, Staff and Students Publications

Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large …

Gna11 Brain Somatic Pathogenic Variant In An Individual With Phacomatosis Pigmentovascularis, Joseph M Sliepka, Sarah C Mcgriff, Linda Z Rossetti, Peyman Bizargity, Haley Streff, Yi-Shan Lee, Hongzheng Dai, Satyamaanasa Polubothu, Grace Lee, Vicky Ren, Jill V Hunter, Daniel J Curry, Fernando Scaglia, Adekunle M Adesina, Irfan Ali, Veronica Kinsler, Lindsay C Burrage, Dana Marafi

Faculty, Staff and Students Publications

OBJECTIVE: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV).

METHODS: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized.

RESULTS: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in

CONCLUSIONS: The finding of this variant in …

Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang

Faculty, Staff and Students Publications

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously …

Defining The Layers Of A Sensory Cilium With Storm And Cryoelectron Nanoscopy, Michael A Robichaux, Valencia L Potter, Zhixian Zhang, Feng He, Jun Liu, Michael F Schmid, Theodore G Wensel

Faculty, Staff and Students Publications

Primary cilia carry out numerous signaling and sensory functions, and defects in them, "ciliopathies," cause a range of symptoms, including blindness. Understanding of their nanometer-scale ciliary substructures and their disruptions in ciliopathies has been hindered by limitations of conventional microscopic techniques. We have combined cryoelectron tomography, enhanced by subtomogram averaging, with superresolution stochastic optical reconstruction microscopy (STORM) to define subdomains within the light-sensing rod sensory cilium of mouse retinas and reveal previously unknown substructures formed by resident proteins. Domains are demarcated by structural features such as the axoneme and its connections to the ciliary membrane, and are correlated with molecular …

Mitochondrial Somatic Mutations And The Lack Of Viral Genomic Variation In Recurrent Respiratory Papillomatosis, Yuhan Hao, Ryan Ruiz, Liying Yang, Antonio Galvao Neto, Milan R Amin, Dervla Kelly, Stratos Achlatis, Scott Roof, Renjie Bing, Kasthuri Kannan, Stuart M Brown, Zhiheng Pei, Ryan C Branski

Faculty, Staff and Student Publications

Recurrent Respiratory Papillomatosis (RRP) is a rare disease of the aerodigestive tract caused by the Human Papilloma Virus (HPV) that manifests as profoundly altered phonatory and upper respiratory anatomy. Current therapies are primarily symptomatic; enhanced insight regarding disease-specific biology of RRP is critical to improved therapeutics for this challenging population. Multiplex PCR was performed on oral rinses collected from twenty-three patients with adult-onset RRP every three months for one year. Twenty-two (95.6%) subjects had an initial HPV positive oral rinse. Of those subjects, 77.2% had an additional positive oral rinse over 12 months. A subset of rinses were then compared …

Enhancing Clinical Concept Extraction With Contextual Embeddings, Yuqi Si, Jingqi Wang, Hua Xu, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Neural network-based representations ("embeddings") have dramatically advanced natural language processing (NLP) tasks, including clinical NLP tasks such as concept extraction. Recently, however, more advanced embedding methods and representations (eg, ELMo, BERT) have further pushed the state of the art in NLP, yet there are no common best practices for how to integrate these representations into clinical tasks. The purpose of this study, then, is to explore the space of possible options in utilizing these new models for clinical concept extraction, including comparing these to traditional word embedding methods (word2vec, GloVe, fastText).

MATERIALS AND METHODS: Both off-the-shelf, open-domain embeddings and …

The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity In Lipid Membranes: Potential Implication For Its Diverse Biological Action, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu

Faculty, Staff and Student Publications

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with …

Integrating Primary Care Into Community Mental Health Centres In Texas, Usa: Results Of A Case Study Investigation, Rebecca Wells, Ellen D Breckenridge, Sasha Ajaz, Aman Narayan, Daniel Brossart, James H Zahniser, Jolene Rasmussen

Faculty, Staff and Student Publications

INTRODUCTION: Despite evidence that people with serious mental illness benefit from receiving primary care within mental health care settings, there is little research on this type of integration. The objective of this study was to characterize how providers and patients experienced implementation of primary care into specialty mental health services.

METHODS: During site visits, study team members interviewed staff and conducted focus groups with patients at 10 United States community mental health centres then beginning to integrate primary into their practices. One year later, follow up phone interviews with key centre staff informants validated and updated findings. Data analysis included …

Pathways To Economic Outcomes And The Impact Of Health: Comparing Hispanic And Non-Hispanic Adults After Foster Care, Susy Villegas Ph.D., Lcsw, Mónica M. Alzate Ph.D., Lcsw, James A. Rosenthal Ph.D., Kirk O'Brien Ph.D, Peter J. Pecora Ph.D.

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

Abstract

This study examines the financial outcomes in adulthood of Hispanics (N = 87) and White (Non-Hispanic, N = 498) persons placed in foster care during childhood. It uses the Casey Family Programs National Alumni Study (CFPNAS) database. Path models including predictors such as gender, education, having a partner, preparation for leaving care, and problem characteristics yielded predominantly similar effects for Hispanic and White Non-Hispanic respondents. The direct effect of physical and mental health conditions such as physical or learning disability, visual or hearing impairments, or DSM disorders more strongly predicted negative outcomes for White (Non-Hispanic) respondents than for Hispanic …