Medicine and Health Sciences Commons^™

Bringing Toxicology Into The 21st Century: A Global Call To Action, Troy Seidle, Martin Stephens

Troy Seidle, PhD

Conventional toxicological testing methods are often decades old, costly and low-throughput, with questionable relevance to the human condition. Several of these factors have contributed to a backlog of chemicals that have been inadequately assessed for toxicity. Some authorities have responded to this challenge by implementing large-scale testing programmes. Others have concluded that a paradigm shift in toxicology is warranted. One such call came in 2007 from the United States National Research Council (NRC), which articulated a vision of ‘‘21st century toxicology” based predominantly on non-animal techniques. Potential advantages of such an approach include the capacity to examine a far greater …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Named Entity Recognition In Chinese Clinical Text, Jianbo Lei

Dissertations & Theses (Open Access)

Objective: Named entity recognition (NER) is one of the fundamental tasks in natural language processing (NLP). In the medical domain, there have been a number of studies on NER in English clinical notes; however, very limited NER research has been done on clinical notes written in Chinese. The goal of this study is to develop corpora, methods, and systems for NER in Chinese clinical text.

Materials and methods: To study entities in Chinese clinical text, we started with building annotated clinical corpora in Chinese. We developed an NER annotation guideline in Chinese by extending the one used in the 2010 …

Three Research Essays On Propensity To Disclose Medical Information Through Formal And Social Information Technologies, Wachiraporn Arunothong

Theses and Dissertations

Abstract

This dissertation, which is comprised of three essays, examined disclosure propensity of healthcare providers from the US and Thailand and disclosure of personal health problems of healthcare consumers in social media context.

Essay 1: A Deterrence Approach in Medical Data Misuse among Healthcare Providers

Information and communication technology (ICT) have long been available for use in health care. With the potential to improve the quality, safety, and efficiency of health care, the diffusion of these technologies has steadily increased in the health care industry. With the adoption of electronic health records, personal electronics devices, internet connections and social network …

Design And Development Of A Linked Open Data-Based Health Information Representation And Visualization System: Potentials And Preliminary Evaluation, Binyam Tilahun, Tomi Kauppinen, Carsten Keßler, Fleur Fritz

Publications and Research

Background: Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse …

Applying Novel Tree-Based Frameworks To Big Data For Classification Of Heart Failure Patients And Prediction Of Clinical Responses, Yan Zhang, Nicholas Downing, Emily Bucholz, Suganthi Balasubramanian, Shu-Xia Li, Tara Liptak, Harlan Krumholz, Mark Gerstein

Yale Day of Data

Over 5 million Americans suffer from heart failure, a condition with a 5-year survival that eclipses all cancers apart from that of lung cancer. Conventional understanding of heart failure is simplistic: it is viewed as a single syndrome, despite real heterogeneity. In addition, models predicting outcomes focus on dichotomous results, like 30-day readmission. A novel approach to classification of heart failure may improve our ability to target interventions, improve patient experiences, and predict outcomes.

The Healthcare Cost and Utilization Project is a family of administrative claims databases that describes patient demographics, comorbidities, procedures, acute care utilization and outcomes, such as …

Identification And Characterization Of Cysteine Protease Genes In Tobacco For Use In Recombinant Protein Production, Kishor Duwadi

Electronic Thesis and Dissertation Repository

Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal based systems. The main technical challenge during this process is to produce sufficient level of proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of a human therapeutic protein interleukin (IL) -10 produced in transgenic tobacco leaves was found to be below the critical level, and is potentially due to degradation by tobacco cysteine proteases (CysPs). …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations & Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations & Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Integrating Domain Knowledge To Improve Signal Detection From Electronic Health Records For Pharmacovigilance, Ning Shang

Dissertations & Theses (Open Access)

The intent of this dissertation is to make a contribution to the field of pharmacovigilance. Pharmacovigilance, also known as post-marketing drug surveillance, is the process of continued monitoring for adverse drug reactions (ADRs) after drugs are released into the market. An ADR is a harmful or unpleasant reaction related to the use of a medical product. ADRs were reported to be between the fourth and sixth leading cause of death in the United States in 1994, accounting for 3-7% of medical hospital admissions. On account of the practice of pharmacovigilance, Vioxx (Rofecoxib) and Avandia (Rosiglitazone) are examples of high profile …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations & Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Structure Based Prediction Of Drug-Protein Interactions At Allosteric Sites: Towards Direct Inhibition Of The Ras Oncogene, Harrison Hocker

Dissertations & Theses (Open Access)

Ras is a monomeric G-protein that mediates multiple signaling pathways. When bound to GTP, Ras binds to and activates effectors and when bound to GDP it does not. Somatic mutations occur in ~15% of all human cancers and cause Ras to be predominantly bound to GTP. Recently, several studies revealed that Ras exists in an ensemble of at least two states when bound to GTP. In the state 1 conformation, Ras is unable to properly bind effectors but holds potential for binding ligands. Conversely, at allosteric sites, state 2 conformations readily bind effectors but not ligands.

To incorporate the flexibility …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

Computational Model For Survey And Trend Analysis Of Patients With Endometriosis : A Decision Aid Tool For Ebm, Salvo Reina, Vito Reina, Franco Ameglio, Mauro Costa, Alessandro Fasciani

COBRA Preprint Series

Endometriosis is increasingly collecting worldwide attention due to its medical complexity and social impact. The European community has identified this as a “social disease”. A large amount of information comes from scientists, yet several aspects of this pathology and staging criteria need to be clearly defined on a suitable number of individuals. In fact, available studies on endometriosis are not easily comparable due to a lack of standardized criteria to collect patients’ informations and scarce definitions of symptoms. Currently, only retrospective surgical stadiation is used to measure pathology intensity, while the Evidence Based Medicine (EBM) requires shareable methods and correct …

Art Or Science?, Allison Marsh

Section 3: Imaging the Fast Moving

No abstract provided.

Examination Of The Snsag Surface Antigen Gene Family In Sarcocystis Neurona, Ablesh Gautam

Theses and Dissertations--Veterinary Science

Sarcocystis neurona is a protozoan parasite that causes the serious neurologic disease equine protozoal myeloencephalitis (EPM). The life cycle of S. neurona progresses through multiple developmental stages that differ morphologically and molecularly. The S. neurona merozoite surface is covered by multiple related proteins, which are orthologous to the surface antigen (SAG) gene family of Toxoplasma gondii. The SAG surface antigens in T. gondii and another related parasite Neospora caninum are life cycle stage-specific and seem necessary for parasite transmission and persistence of infection. The present research was conducted to explore the gene family of SnSAGs in S. …

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

Undergraduate Research Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Finding Them Before They Find Us: Informatics, Parasites, And Environments In Accelerating Climate Change, Daniel R. Brooks, Eric P. Hoberg, Walter A. Boeger, Scott Lyell Gardner, Kurt E. Galbreath, David Herczeg, Hugo H. Mejía-Madrid, S. Elizabeth Rácz, Altangerel Tsogtsaikhan Dursahinhan

Harold W. Manter Laboratory of Parasitology: Faculty and Staff Publications

Parasites are agents of disease in humans, livestock, crops, and wildlife and are powerful representations of the ecological and historical context of the diseases they cause. Recognizing a nexus of professional opportunities and global public need, we gathered at the Cedar Point Biological Station of the University of Nebraska in September 2012 to formulate a cooperative and broad platform for providing essential information about the evolution, ecology, and epidemiology of parasites across host groups, parasite groups, geographical regions, and ecosystem types. A general protocol, documentation–assessment–monitoring–action (DAMA), suggests an integrated proposal to build a proactive capacity to understand, anticipate, and respond …

Space-Time Statistical Analysis Of Malaria Morbidity Incidence Cases In Ghana: A Geostatistical Modelling Approach, Simon K. Appiah

Theses: Doctorates and Masters

Malaria is one of the most prevalent and devastating health problems worldwide. It is a highly endemic disease in Ghana, which poses a major challenge to both the public health and socio-economic development of the country. Major factors accounting for this situation include variability in environmental conditions and lack of prevention services coupled with host of other socio-economic factors. Ghana’s National Malaria Control Programme (NMCP) risk assessment measures have been largely based on household surveys which provided inadequate data for accurate prediction of new incidence cases coupled with frequent incomplete monthly case reports. These raise concerns about annual estimates on …

Evolutionary Approaches For Feature Selection In Biological Data, Vinh Q. Dang

Theses: Doctorates and Masters

Data mining techniques have been used widely in many areas such as business, science, engineering and medicine. The techniques allow a vast amount of data to be explored in order to extract useful information from the data. One of the foci in the health area is finding interesting biomarkers from biomedical data. Mass throughput data generated from microarrays and mass spectrometry from biological samples are high dimensional and is small in sample size. Examples include DNA microarray datasets with up to 500,000 genes and mass spectrometry data with 300,000 m/z values. While the availability of such datasets can aid in …

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

Developing A Risk Model For In-Hospital Adverse Events Following Implantable Cardioverter-Defibrillator Implantation.Pdf, Michael Mirro

Michael Mirro, MD

Introduction To Genome Browsers, Rolando Garcia-Milian

Rolando Garcia-Milian

In this workshop we will learn how to navigate the genome browsers from NCBI's Genome Workbench, UCSC Genome Browser, and Ensembl. These browsers are valuable tools when identifying, localizing genes, and looking at their information in the genomic context. By using concrete examples, it will be shown how to locate a human gene, download a gene sequence and its upstream sequence, locate Single Nucleotide Polymorphisms (SNPs) and conserved regions, and use the browsers to download results in a batch.