Medicine and Health Sciences Commons^™

Design And Architecture Of An Ontology-Driven Dialogue System For Hpv Vaccine Counseling, Amith Faheem Muhammad

Dissertations and Theses (Open Access)

Speech and conversational technologies are increasingly being used by consumers, with the inevitability that one day they will be integrated in health care. Where this technology could be of service is in patient-provider communication, specifically for communicating the risks and benefits of vaccines. Human papillomavirus (HPV) vaccine, in particular, is a vaccine that inoculates individuals from certain HPV viruses responsible for adulthood cancers - cervical, head and neck cancers, etc. My research focuses on the architecture and development of speech-enabled conversational agent that relies on series of consumer-centric health ontologies and the technology that utilizes these ontologies. Ontologies are computable …

Effective Statistical Energy Function Based Protein Un/Structure Prediction, Avdesh Mishra

LSU New Orleans Theses and Dissertations

Proteins are an important component of living organisms, composed of one or more polypeptide chains, each containing hundreds or even thousands of amino acids of 20 standard types. The structure of a protein from the sequence determines crucial functions of proteins such as initiating metabolic reactions, DNA replication, cell signaling, and transporting molecules. In the past, proteins were considered to always have a well-defined stable shape (structured proteins), however, it has recently been shown that there exist intrinsically disordered proteins (IDPs), which lack a fixed or ordered 3D structure, have dynamic characteristics and therefore, exist in multiple states. Based on …

Biological Pathway Involvement In Melanoma Heterogeneity And Drug-Induced Resistance, Sarah V. Pack

STAR Program Research Presentations

Tumors develop resistance to numerous drug therapies, and this remains a major obstacle in treating many types of non-surgical cancers. Melanoma provides a good model system for studying drug resistance in cancer due to its high propensity to incur resistance after a significant initial response to a drug. Genes that are highly expressed in melanoma cancer cells have been studied, but in order to further understand the collective function of these highly expressed genes we must analyze gene sets, or pathways. A single gene’s function is rarely independent of other genes, and pathway analysis takes this into account.

Our objective …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar

Dissertations and Theses (Open Access)

Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …

Role Of Gp120 Glycosylation In Sexual Transmission Of Hiv, Yingxue Sun, Adam Meadows, Najwa Zebian, Eric Arts, Carole Creuzenet

Western Research Forum

Background:

In chronic HIV patients, the viral populations are genetically diverse due to mutations introduced by the viral reverse transcriptase during HIV replication. However, more than 80% new infections result from single transmission founder (TF) viruses; therefore, targeting the TFs is key to control AIDS worldwide.

Gp120 is a glycosylated envelope protein required for HIV infection, propagation, and transmission. Glycans on gp120 influence HIV infectivity through their interactions with lectins, the carbohydrate-binding immune proteins in the host mucosa. To transmit sexually, viruses must overcome the lectin traps to access more target T cells.

Hypothesis:

TF viruses are less likely to …

An Application Of The Modifiable Areal Unit Problem: Optimizing Cluster Method Parameters To Produce Predictive Data For Hiv Outbreaks, Connor J. Chato, Art Fy Poon

Western Research Forum

Background

A popular approach to study HIV outbreaks is to cluster cases based on genetic similarity. However, there is no widely-used statistical criterion which optimizes the parameters for sequence-based clustering methods. The relationship between a cluster-defining similarity threshold and it’s associated set of clusters can be analogized to the aggregation level in the Modifiable Areal Unit Problem (MAUP).

Hypothesis

Based on the selection of aggregation level for study partitions in MAUP, we present a statistical framework to optimize the similarity threshold for pairwise distance algorithm TN93 (http://github.com/veg/tn93). We hypothesize that defining this threshold includes case connections such that …

Evolutionary Dynamics Of Influenza Type B In The Presence Of Vaccination: An Ecological Study, Lindsey J. Fiedler

USF Tampa Graduate Theses and Dissertations

Understanding the evolutionary dynamics of influenza type B in human hosts is a public health concern as we strive to minimize the disease burden in seasonal epidemics. Vaccination is considered the best defense against contracting influenza, and everyone over the age of 6 months is advised to get vaccinated before each season. The effect that vaccine-acquired immunity has on the evolution of influenza B remains unclear. In the U.S., vaccine-uptake is irregular across the states, and the differing coverages present an opportunity to study how vaccination influences viral evolution. This thesis analyzes the evolutionary patterns of influenza B in the …

An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese

Theses and Dissertations

The drug discovery process is an extremely long and expensive process that modern computational methods help to alleviate. Through the use of computational methods, we provide information and insight into the activation methods of class B GPCRs so that future drugs can be developed to have less side effects. The first study focuses on the corticotropin releasing factor receptor, which is a good drug target for anxiety and depression. A mechanism of activation was theorized which focuses less on molecular switches (as has been the focus of several papers) and more on large scale conformation at the intracellular region of …

Rising Rural Body-Mass Index Is The Main Driver Of The Global Obesity Epidemic In Adults, Con Burns, Tara Coppinger, Janette Walton, Et Al

Publications

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to …

Anti-Crispr Vs. Crispr: The Evolutionary Arms Race Between Microorganisms, Rachael M. St. Jacques

Masters Theses, 2010-2019

CRISPR arrays are a defense mechanism employed by bacteria against viral invaders. Cas proteins do the work in detecting, capturing, and integrating the viral DNA into the CRISPR array (Barrangou et al., 2007). Anti-CRISPR proteins are produced by phages, viruses that infect bacteria, to stop the bacterial host’s CRISPR-Cas complex from interrupting the phage life cycle (Bondy-Denomy, et al., 2015).

SEA-PHAGES is a course-based bacteriophage research network composed of 120 colleges and known at James Madison University as Viral Discovery. JMU uses the unsequenced Streptomyces griseus ATCC10137 as a host for bacteriophage discovery and propagation, and in this study we …

Characterization Of Extracellular Vesicles From Human Diabetic Retinopathy Retinal Tissue In Vitro And From Urine Of Human Patients With Diabetic Retinopathy, Jason Mighty

Dissertations, Theses, and Capstone Projects

Diabetic Retinopathy (DR) is a neurovascular complication associated with diabetes mellitus that affects approximately 120 million people worldwide and its prevalence is expected to reach 190 million by 2030. DR diagnosis is accomplished with fundus ophthalmoscopy often when retinal damage and vision loss have already occurred. A group of biomarker being explored for early detection of diseases are extracellular vesicles (EVs), which are nanometer diameter lipid enclosed vesicles, released from all cell types and containing genetic cargo reflective of releasing cell state. EV biomarkers are currently being explored to help monitor disease predisposition, pathogenesis and response to treatment. While an …

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

Dissertations and Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis …

Contribution Of Retrotransposons To Breast Cancer Malignancy, Isaac D. Raplee

USF Tampa Graduate Theses and Dissertations

The components contributing to cancer progression, especially the transition from early to invasive are unknown. Consequently, the biological reasons are unclear as to why some patients diagnosed with atypia and ductal carcinoma in situ (DCIS) never progress into invasive breast cancer. The “one gene at a time” approach does not sufficiently predict progression. To elucidate the early stage progression to invasive ductal cancer, expression signature of transcripts and transposable elements in micropunched samples of formalin-fixed, paraffin embedded (FFPE) tissue was conducted. A bioinformatics pipeline to analyze poor quality, short reads (>36 nts) from RNA-Seq data was created to compare …

Genomics And Transcriptomics Approaches To Understanding Drug Resistance Mechanisms In The Malaria Parasite Plasmodium Falciparum, Justin Allan Gibbons

USF Tampa Graduate Theses and Dissertations

The malaria parasite Plasmodium falciparum is responsible for about 500,000 deaths a year and is evolving resistance to the front-line treatment of artemisinin-based combination therapy. Resistance is currently confined to South East Asia, however millions of lives will be at risk if resistance spreads to Africa. Understanding the mechanism of resistance to artemisinins would aid containment strategies to prevent the spread of artemisinin resistance. There is also an urgent need to accelerate drug discovery since drug resistance has already been documented to all existing antimalarials. Here, I report on our efforts to understand the function of the gene k13, the …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Impact Of The Affordable Care Act On Colorectal Cancer Screening, Incidence, And Survival In Kentucky, Tong Gan, Heather F. Sinner, Samuel C. Walling, Quan Chen, Bin Huang, Thomas C. Tucker, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Surgery Faculty Publications

Background

Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky.

Study Design

The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years) undergoing CRC …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll

Biochemistry Publications

Accuracy of the automated dicentric chromosome (DC) assay relies on metaphase image selection. This study validates a software framework to find the best image selection models that mitigate inter-sample variability. Evaluation methods to determine model quality include the Poisson goodness-of-fit of DC distributions for each sample, residuals after calibration curve fitting and leave-one-out dose estimation errors. The process iteratively searches a pool of selection model candidates by modifying statistical and filter cut-offs to rank the best candidates according to their respective evaluation scores. Evaluation scores minimize the sum of squared errors relative to the actual radiation dose of the calibration …

Data Collection Curated With An Application Ontology Describes The Methods And Results Upon Performing An Ex-Vivo Voltage-Clamp Assay On Outer Hair Cells Of The Mammalian Cochlea, Brenda Farrell, Jason Bengtson

Research Data

This data collection describes the electrical properties of outer hair cells isolated from the mammalian cochlea of the domestic guinea pig. This data was obtained by performing whole-cell patch clamp voltage clamp assay on cells and monitoring the electrical admittance during a DC voltage ramp. The membrane capacitance was then calculated at each membrane potential from this admittance, and the voltage-independent and voltage-dependent membrane capacitance was determined upon further analysis. In some case the DC conductance was also measured by interrogation of the cell with voltage-step function which was calculated from the change in the mean steady-state current with respect …

Differential Abundance And Clustering Analysis With Empirical Bayes Shrinkage Estimation Of Variance (Dasev) For Proteomics And Metabolomics Data, Zhengyan Huang

Theses and Dissertations--Epidemiology and Biostatistics

Mass spectrometry (MS) is widely used for proteomic and metabolomic profiling of biological samples. Data obtained by MS are often zero-inflated. Those zero values are called point mass values (PMVs). Zero values can be further grouped into biological PMVs and technical PMVs. The former type is caused by the absence of components and the latter type is caused by detection limit. There is no simple solution to separate those two types of PMVs. Mixture models were developed to separate the two types of zeros apart and to perform the differential abundance analysis. However, we notice that the mixture model can …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Deep Patient Representation Of Clinical Notes Via Multi-Task Learning For Mortality Prediction, Yuqi Si, Kirk Roberts

Faculty, Staff and Student Publications

We propose a deep learning-based multi-task learning (MTL) architecture focusing on patient mortality predictions from clinical notes. The MTL framework enables the model to learn a patient representation that generalizes to a variety of clinical prediction tasks. Moreover, we demonstrate how MTL enables small but consistent gains on a single classification task (e.g., in-hospital mortality prediction) simply by incorporating related tasks (e.g., 30-day and 1-year mortality prediction) into the MTL framework. To accomplish this, we utilize a multi-level Convolutional Neural Network (CNN) associated with a MTL loss component. The model is evaluated with 3, 5, and 20 tasks and is …

Statistical Methods For Joint Analysis Of Multiple Phenotypes And Their Applications For Phewas, Xueling Li

Dissertations, Master's Theses and Master's Reports

Genome-wide association studies (GWAS) have successfully detected tens of thousands of robust SNP-trait associations. Earlier researches have primarily focused on association studies of genetic variants and some well-defined functions or phenotypic traits. Emerging evidence suggests that pleiotropy, the phenomenon of one genetic variant affects multiple phenotypes, is widespread, especially in complex human diseases. Therefore, individual phenotype analyses may lose statistical power to identify the underlying genetic mechanism. Contrasting with single phenotype analyses, joint analysis of multiple phenotypes exploits the correlations between phenotypes and aggregates multiple weak marginal effects and is therefore likely to provide new insights into the functional consequences …

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …

Pasnet: Pathway-Associated Sparse Deepneural Network For Prognosis Prediction From High-Throughput Data, Jie Hao, Youngsoon Kim, Tae-Kyung Kim, Mingon Kang

Faculty Articles

Background: Predicting prognosis in patients from large-scale genomic data is a fundamentally challenging problem in genomic medicine. However, the prognosis still remains poor in many diseases. The poor prognosis maybe caused by high complexity of biological systems, where multiple biological components and their hierarchical relationships are involved. Moreover, it is challenging to develop robust computational solutions with high-dimension, low-sample size data. Results: In this study, we propose a Pathway-Associated Sparse Deep Neural Network (PASNet) that not only predicts patients’ prognoses but also describes complex biological processes regarding biological pathways for prognosis. PASNet models a multilayered, hierarchical biological system of genes …

Phr: Patient Health Record, Quinn Nelson

Theses/Capstones/Creative Projects

The rapid development of information technology systems has expanded into multiple disciplines and results in systems that are limited by initial design and implementation: the Healthcare Information Technology (HIT) space is no different. The introduction of the Electronic Health Record (EHR) system has changed the way healthcare operates. Initial designs of these systems were focused on serving the needs of insurance companies and healthcare billing departments. Research shows that the design of EHR systems negatively impact provider-patient interactions and the care they receive. This capstone project capitalizes on the collaboration efforts between UNO and UNMC – by joining a research …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

Effects Of A Community Population Health Initiative On Blood Pressure Control In Latinos, James R Langabeer, Timothy D Henry, Carlos Perez Aldana, Larissa Deluna, Nora Silva, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Background Hypertension remains one of the most important, modifiable cardiovascular risk factors. Yet, the largest minority ethnic group (Hispanics/Latinos) often have different health outcomes and behavior, making hypertension management more difficult. We explored the effects of an American Heart Association-sponsored population health intervention aimed at modifying behavior of Latinos living in Texas. Methods and Results We enrolled 8071 patients, and 5714 (65.7%) completed the 90-day program (58.5 years ±11.7; 59% female) from July 2016 to June 2018. Navigators identified patients with risk factors; initial and final blood pressure ( BP ) readings were performed in the physician's office; and interim …

Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile, Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli …