Medicine and Health Sciences Commons^™

Development, Validation, And Diagnostic Performance Of A Novel Radiomic Model For Predicting Prostate Cancer Recurrence, Linda M. Huynh

Theses & Dissertations

Multi-parametric magnetic resonance imaging (MP-MRI)-derived radiomics have been shown to capture sub-visual patterns for the quantitative characterization of prostate cancer (PC) phenotypes. The present dissertation seeks to develop, evaluate, and compare the performance of an MRI-derived radiomic model for the prediction of PC recurrence following definitive treatment with radical prostatectomy (RP).

MP-MRI was obtained from 339 patients who had a minimum of 2 years follow-up following RP at three institutions. The prostate was manually delineated as the region of interest and 924 radiomic features were extracted. All features were evaluated for stability via intraclass correlation coefficient (ICC) and image normalization …

Evaluating The Impact Of Routine Enteral Iron Fortification On Gastrointestinal Dysbiosis In Premature Infants, Matthew Van Ormer

Theses & Dissertations

The gastrointestinal microbiome in preterm infants bears significant influence on optimal outcomes – dysbiosis is shown to substantially increase the risk of the life-threatening necrotizing enterocolitis, whereas optimal microbiome composition improves nutrient digestion and immune function. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurological development. However, excess colonic iron exhibits potent oxidation capacity and alters the competitive environment of microbes – potentially facilitating the proliferation of pathological bacterial strains in the gut. Of note, breastfed preterm infants routinely receive iron fortification starting at 14 days of life and are …

Use Of Pre-Transplant Cmi To Predict Infection And Mortality Post-Cardiac Transplantmortality Post-Cardiac Transplant, Chetaj A. Mahabir

Theses & Dissertations

This paper discusses a study investigating the relationship between the cell-mediated immunity (CMI) level before cardiac transplant and the incidence of infection and mortality after the transplant. CMI is an important measure of a person's immune system. The study included 126 patients who underwent cardiac transplants between September 2011 and January 2020. Out of these, 21 patients had a low CMI level (<225), and 105 had a high CMI level (≥ 225) before transplant. The mean CMI level in the low CMI group was 175.3, while in the high CMI group, it was 479.9. The two groups were similar except for the lower white cell count and cardiac output in the CMI< 225 groups and the higher Caucasian demographic in the CMI≥ 225 groups. The study concludes that patients with lower CMI levels before cardiac transplant have a higher risk of infection (p=0.052) and mortality (p=0.005) one year after the transplant. The risk of dying for patients with CMI <225 is 12.9 times the risk of dying for patients with CMI ≥ 225 after adjusting for the other covariates in the model. However, this study has some limitations including its retrospective nature, small sample size, and single-center design. Further studies are needed to replicate these findings and investigate the optimal immunosuppressive regimens based on baseline CMI levels.

Frailty Determination And Responsiveness In Left Ventricular Assist Devices, Sarah Schroeder

Theses & Dissertations

Frailty, the state of being vulnerable with susceptibility to decreased age-related physical reserve, is found in 56-79% of adults with end-stage HF receiving durable left ventricular assist device (dLVAD) therapy. Frailty increases risk of adverse events, including increased mortality in the dLVAD population, but less is known about depression, quality of life (QOL), cognition and frailty responsiveness. Therefore, we aimed to describe and compare frailty (5-Meter Walk Test, 5MWT), depression (Patient Health Questionnaire-9, PHQ-9), quality of life (EQ5D Visual Analog Scale, EQ-5D VAS) and cognition (Trailmaking B) from pre- to 12-months post-dLVAD We also compared demographics, clinical characteristics, and post-dLVAD …

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du

Theses & Dissertations

The prevalence of nonalcoholic fatty liver disease (NAFLD) among Chinese young adults (CYA) aged 18-25 years ranges from 4.7% to 15.1% and has kept increasing in recent years. Previous studies reported limited awareness and knowledge of NALFD among middle-aged and older Chinese populations, however, they have not investigated awareness in CYA, for which there is no well-validated questionnaire. There is currently no efficacious educational intervention on NAFLD for CYA.

The objectives were 1) to develop and validate a questionnaire which can be used to assess the awareness and knowledge of NAFLD among CYA; 2) to assess the awareness and knowledge …

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

Feasibility And Efficacy Of Bisphosphonate Use For The Prevention Of Bone And Muscle Loss, Laura E. Flores

Theses & Dissertations

Loss of bone and muscle mass often occurs in tandem, increasing the risk of fragility fractures. Whereas many drugs are approved for the treatment of bone loss, there are few treatments available for the concomitant loss of bone and muscle. Identification of a treatment to mitigate pathologic bone and muscle atrophy has the potential to impact countless populations and influence approaches for healthy aging. Bisphosphonates have emerged as a potential treatment for both bone and muscle loss in cellular, murine, and observational human studies. Our findings of modest weight maintenance in postmenopausal women treated with 12-months of risedronate, relative to …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Post-Transplant Hepatic Graft Fibrosis In Pediatric Liver-Inclusive Transplant Recipients, Hanh D. Vo

Theses & Dissertations

Hepatic graft fibrosis is a common histologic finding following pediatric liver transplant (LT) that may affect the long-term graft outcome. Hence, it is essential to identify hepatic graft fibrosis at a stage where fibrosis is not yet clinically apparent but has the potential for progression to initiate appropriate intervention and prevent its progression. Liver biopsy is the gold standard for fibrosis staging, but it is invasive, requires general anesthesia in children, and has potential complications. Our long-term goal is to implement non-invasive tests to assess and monitor the progression of hepatic graft fibrosis in liver-inclusive transplant children. The work presented …

Glad To Be Out. I Was Running Out Of Womb: A Study Of Omega-6 And Omega-3 Fatty Acid Metabolites At Delivery And Their Relationship To Infant Growth, Prematurity, And Admission To The Neonatal Intensive Care Unit, Maranda Thompson

Theses & Dissertations

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled it can lead to poor infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and omega-6 fatty acids have been shown to be metabolized into bioactive metabolites that effect inflammation. The presence and importance of these metabolites at the time of delivery are not well understood. Therefore, the purpose of this dissertation was to first quantify omega-3 and omega-6 metabolites in maternal plasma, cord plasma, and placental tissue. Then the relationships between metabolites and infant outcomes, including birth weight percentile, length percentile, head circumferences …

The Ecology Of Mental Health And The Impact Of Barriers On Mental Health Service Utilization, Alisha Aggarwal

Theses & Dissertations

Mental health has emerged as a major public health concern in recent times with several disparities and barriers related to adequate health service utilization. Different age groups experience diverse symptoms and face distinct barriers in accessing and utilizing healthcare. Policies like Mental Health Parity and Addiction Equity Act and the Patient Protection and Affordable Care Act were launched to improve insurance coverage and delivery of mental health services. However, a large gap of unmet needs exists for adequate mental health service utilization in the country. This dissertation aims to describe the financial and non-financial barriers to mental health service utilization …

Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner

Theses & Dissertations

Antibiograms are critical for choosing empiric antimicrobial therapy. Cumulative antibiograms, which aggregate susceptibility data, can mask differences within specific patient subsets or clinical syndromes. This dissertation was done to determine if antibiotic susceptibilities showed substantial differences when comparing stratified antibiograms to cumulative antibiograms.

Antibiotic susceptibility data was retrospectively obtained from Nebraska Medicine January 1, 2017 – December 31, 2019 for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The University of Nebraska Medical Center’s web antibiogram clinical decision support tool was used to export the data. Bacteria-antibiotic susceptibility rates of stratified antibiograms …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Apixaban To Prevent Thrombosis In Adult Patients Treated With Asparaginase, Krishna Gundabolu

Theses & Dissertations

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved dramatically after intensification of the multi-agent chemotherapy backbone over a period of time starting from 1960’s, and asparaginase (ASP) is an important part of this success story. Adoption of such strategy in adult ALL and other high grade lymphoid neoplasms had been difficult due to higher anticipated toxicities including thrombosis. Many thrombosis prevention strategies including antithrombin (AT) replacement, Enoxaparin, unfractionated heparin (UFH) was studied but there is no firmly established evidence-based approach yet. We report the safety and efficacy of thrombosis prophylaxis with apixaban 2.5 mg orally twice daily for …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

A Collection Of Research In Transplantation Surgery: The Importance Of Assessing Outcomes In A Field Dependent On The Availability Of Limited Resources, Amy J. Hargrove

Theses & Dissertations

This thesis is a collection of three independent projects related to transplantation surgery. In summary, project I involves an assessment of long-term quality of life outcomes of intestinal transplantation in pediatric patients who are now in adulthood, with comparison to other solid organ transplant patients. Health related quality of life surveys were completed in 14 adult patients who underwent intestine, liver, or kidney transplants as children. Project II evaluates pre-surgical characteristics of patients undergoing liver transplant to assess predictive factors for the need of venovenous bypass utilization intraoperatively by assessing trends at the University of Nebraska Medical Center in 95 …

Proof Of Concept: The Use Of Renal Biomarkers In Critically Ill Pediatric Patients For Therapeutic Drug Monitoring, Christopher Lee Shaffer

Theses & Dissertations

Acute kidney injury (AKI) is a serious and common complication in critically ill pediatric patients. The incidence of pediatric AKI continues to increase, especially in patients who undergo surgical correction of congenital heart defects. Serum creatinine and urine output are the most commonly used tools to assess renal function, with international guidelines standardizing AKI-definitions based upon these parameters. However, changes in serum creatinine can occur 24 hours or later after a renal insult event, delaying the diagnosis and potential interventions to reverse injury. It is critical to identify endogenous renal biomarkers within the pediatric population that are both timely and …

Molecular Pathogenesis Of A Novel Subgroup Of Peripheral T-Cell Lymphomas, Jiayu Yu

Theses & Dissertations

Peripheral T-cell Lymphoma (PTCL) consists of numerous distinct disease entities. With the current diagnostic criteria over a third of the cases cannot be further classified and are called "not otherwise specified" (PTCL-NOS). Using gene expression profiling (GEP) of tumors, we identified two novels PTCL-NOS molecular subgroups either characterized by high expression of GATA3 (33%), which is associated with Th2 cell differentiation, or high expression of TBX21 (49%) which regulates Th1 cell maturation. Therefore, stratifying patients for diagnosis and identifying the underlying genetic basis to improve clinical therapy becomes critical to prognosis.

First, we performed DNA copy number analysis by using …

Superoxide And Pulmonary Hypertension, Tammy Wichman

Theses & Dissertations

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease, which is progressive and fatal despite advances in therapy. Animal models have shown that oxidative stress may be pathogenic in PAH. We hypothesize that oxidative stress, as measured by increased levels of a specific reactive oxygen species, superoxide (O₂^•-), mayplay a role in PAH in humans. Using a novel application of electron paramagnetic resonance (EPR) spectroscopy, we initially evaluated whether levels of O₂^•- from whole blood collected from the pulmonary artery collected during right heart catheterization (RHC) would correlate with O₂^•- levels in peripheral …

Insights Into Cutaneous Squamous Cell Carcinoma Pathogenesis And Metastasis Using A Bedside-To-Bench Approach, Marissa Lobl

Theses & Dissertations

Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer, affecting 1,000,000 people in the United States annually and causing approximately 9,000 deaths. SCC and basal cell carcinoma are the most common types of skin cancer arising in the superficial squamous cells or deeper basal cells of the epidermis, respectively. SCC is more likely to invade and metastasize, while basal cell cancer tends to grow locally. While the majority of cases of SCC are cured by surgery alone, approximately 2-5% of SCCs metastasize, at which point outcomes may be poor. Specific patient groups, particularly immunosuppressed patients, have a …

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 …

Clinical Consequences And Determinants Of False Positive Blood Cultures In Adult Hospitalized Patients, Sidra Liaquat

Theses & Dissertations

Blood cultures are the gold standard for detecting blood stream infections. However, in the US, 0.6-6% of all blood cultures get contaminated leading to adverse clinical outcomes such as unnecessarily prolonged hospital stay and antibiotic therapy. Using electronic medical records, we explored the clinical outcomes and patient-specific risk factors of contaminated blood cultures in an era where rapid blood culture testing was being utilized to provide blood culture results within hours. Rapid blood culture test results can help clinicians in early and more effective management of patients with contaminated blood cultures, thus improving clinical outcomes. We also studied the impact …

Fire Service Covid-19 Infection Prevention And Control Policy Comparison, Saaddedine Dichari

Theses & Dissertations

To date, there have been over 2.7 million deaths and more than 126 million cases attributed to the COVID-19 pandemic (JHU, 2021). This pandemic has affected nearly every aspect of daily life. Among those impacted are U.S. firefighters, as they provide many services beyond simply extinguishing structure fires and are frequently dual certified as emergency medical technicians. Many of the victims of this pandemic have relied on first responders to provide them with emergency medical care and hospital transport. When caring for these infected patients, firefighters have an increased risk of exposure and must be provided with adequate …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

The Driving Simulator Visual Field In Glaucoma – A Novel Task To Test Available Field Of View, Deepta Ghate

Theses & Dissertations

Glaucoma causes peripheral vision loss and impaired driving performance. We developed a novel driving simulator visual field task (DSVF) in a panoramic driving simulator to map the available field of view under different perceptual task loads in naturalistic settings. Our hypothesis is that “available field of view” will decrease with increasing task load in both glaucoma subjects and controls. This is a cross-sectional study with 28 glaucoma subjects and 19 controls. DSVF (60̊ x 20̊ visual field at 2.5 m) was tested in a high-fidelity interactive driving simulator in 4 different scenarios: a) no distractions b) no driving condition with …

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 …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

The Role Of Vgll4 And Mark2-Hdac Axis In Mitosis And Cancer, Yongji Zeng

Theses & Dissertations

The Hippo pathway is an evolutionarily conserved signaling pathway that plays important roles in stem cell biology, tissue homeostasis, and cancer development. The Hippo core signaling pathway features a kinase cascade consisting of mammalian sterile-20 like protein 1/2 (Mst1/2) and large tumor suppressor 1/2 (Lats1/2). Inactivation of the Hippo pathway is correlated with the promotion of proliferation and anti-apoptosis through activation of the transcriptional co-activator Yes-associated protein (YAP). YAP functions through binding with TEA-domain transcription factors (TEAD1–4) to activate target genes.

Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo-Yes associated protein (YAP) pathway. Vgll4 inhibits cell proliferation …