Bioinformatics Commons^™

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Reach, Effectiveness, Adoption, And Maintenance Of Mobile Electronic Clinical Decision Support Tools Deployed As Part Of National Quality Improvement Projects, Ellen K. Kerns

Theses & Dissertations

Electronic clinical decision support (ECDS) tools are often developed within quality improvement (QI) projects to increase adherence with the latest clinical practice guidelines. However, the potential reach and maintenance of ECDS use beyond the time and location of their associated project are very limited. Deploying ECDS using a mobile app (mECDS) has shown the potential to be a viable method of overcoming these limitations. However, it is unclear what pattern the reach and adoption of such a tool might follow and what effect this use has on clinical practice. Our team developed an app which contained two different mECDS tools …

The Evolving Management Of Aortic Valve Disease: Trends In The Utilization And Cost Of Savr, Tavr, And Medical Therapy, Andrew Goldsweig

Theses & Dissertations

Aortic stenosis (AS) and regurgitation (AR) may be treated with surgical aortic valve replacement (SAVR), transcatheter AVR (TAVR), or medical therapy (MT). Data are lacking regarding usage and cost of SAVR, TAVR, and MT for patients hospitalized with aortic valve disease. From the Nationwide Readmissions Database, we determined utilization and cost trends for SAVR, TAVR, and MT in patients with aortic valve disease admitted 2012-2016 for valve replacement, heart failure, unstable angina, non-ST-elevation myocardial infarction, or syncope. From 2012 through 2016, there was a 48.1% increase in the number of patients hospitalized for aortic valve disease annually. Overall, 19.9%, 6.7%, …

An Evaluation Of The Use Of A Clinical Research Data Warehouse And I2b2 Infrastructure To Facilitate Replication Of Research, Bret Gardner

Theses & Dissertations

Replication of clinical research is requisite for forming effective clinical decisions and guidelines. While rerunning a clinical trial may be unethical and prohibitively expensive, the adoption of EHRs and the infrastructure for distributed research networks provide access to clinical data for observational and retrospective studies. Herein I demonstrate a means of using these tools to validate existing results and extend the findings to novel populations. I describe the process of evaluating published risk models as well as local data and infrastructure to assess the replicability of the study. I use an example of a risk model unable to be replicated …

Functional Signature Ontology-Based Identification And Validation Of Novel Therapeutic Targets And Natural Products For The Treatment Of Cancer, Beth Neilsen

Theses & Dissertations

Multiple studies have revealed that Ras-driven tumors acquire vulnerabilities by adapting cellular mechanisms that promote uncontrolled proliferation and suppress apoptosis. Kinase Suppressor of Ras 1 (KSR1) modulates ERK activation downstream of oncogenic Ras, and knockdown of KSR1 selectively kills malignant, Ras-driven cancer cells, but does not kill immortalized, non-transformed human colon epithelial cells (HCECs). KSR1^-/- mice are fertile and phenotypically normal, but resistant to Ras-driven tumor formation suggesting KSR1 represents a vulnerability in cancer cells.

To identify additional vulnerabilities in cancer, a screening approach termed Functional Signature Ontology (FUSION) was used to screen 14,355 genes and 1,200 natural product …