Medicine and Health Sciences Commons^™

Bridging The Information Divide: Leveraging The Learning Health System To Understand Rural-Urban Health Disparities In The Covid-19 Era, Alfred J. Anzalone

Theses & Dissertations

The examination of healthcare disparities, which the COVID-19 pandemic exacerbated, revealed a pronounced divide between rural and urban settings. This divide particularly underscored the challenges of integrating rural healthcare into the Learning Health System (LHS) and utilizing real-world data (RWD) in response to a public health emergency. Our investigation expanded the growing body of literature on the rural mortality penalty, encompassing the period following the COVID-19 pandemic. By employing an LHS-enabled centralized platform of RWD, we assessed the impact of rurality on adverse COVID-19 outcomes (Aim 1), focusing on inpatient adverse events and the effectiveness of treatments and vaccinations across …

Cognitive Control In Health And Disease: A Dynamic Approach To Mapping Oscillatory Activity Across The Lifespan, Mikki Schantell

Theses & Dissertations

Cognitive control is critical for flexibly adapting goal-directed behaviors to meet the demands of dynamically changing environments. The neural oscillatory dynamics serving cognitive control undergo changes across the lifespan, both in health and disease, with impairments in cognitive control functions being broadly implicated across a multitude of psychiatric disorders. Despite this, the trajectory of the population-level neural oscillatory dynamics supporting cognitive control across the lifespan remain poorly characterized, presenting challenges in fully understanding perturbations to these systems relative to one’s stage in neuronal maturation. Herein, we used the Eriksen flanker task during magnetoencephalographic (MEG) recording to map the neural oscillatory …

Using Readiness To Change For Dietary Modification In A Rural Primary Care Setting, Rebecca Johnson Beller

Theses & Dissertations

Cardiovascular disease is a prevalent noncommunicable disease. Modifying lifestyle behavior can decrease cardiovascular disease morbidity and mortality outcomes. This dissertation's purpose was to explore behavioral change interventions with dietary strategies to reduce cardiovascular disease rates. The integrative review explored aspects of dietary strategies in the primary care setting. Despite the importance of diverse studies, comparing all the components results in limited generalizability. In the following chapter, a cross-sectional study elicited healthcare professionals’ perceptions of the usefulness of a readiness for lifestyle change tool in clinical practice. Currently, a common, widespread adoption of a readiness for lifestyle change tool is not …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

Facilitators And Barriers To Implementing Effective Interprofessional Education: A Mixed Methods Study Of Academic Health Institutions With Centralized Interprofessional Education Administrative Structures, Liliana Bronner

Theses & Dissertations

Interprofessional education (IPE) is pivotal in preparing future healthcare professionals for collaborative practice, yet its effective implementation remains challenging. The purpose of this mixed methods study of multiple academic health institution cases was to explore and understand how early and late IPE adopters perceive effective IPE implementation in academic health institutions. Combining frameworks for complex innovation implementation and curriculum development with surveys and interviews reveals the facilitators and barriers of effective IPE implementation. Consistent with the framework for complex innovation implementation, leadership and administrative support, resource allocation, logistical planning, and program evaluation emerged as key facilitators of effective IPE implementation. …

The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps

Theses & Dissertations

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals …

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

A Tale Of Two Proteins: An Investigation Of Recruitment Of Eukaryotic Proteins Fli1 And Lrrf1 To The Chlamydial Inclusion Membrane, Natalie Sturd

Theses & Dissertations

Chlamydia trachomatis is the pathogen responsible for the majority of infectious blindness and sexually transmitted bacterial infections worldwide. As an obligate intracellular pathogen, it establishes a niche within a pathogen-specific vacuole, termed the chlamydial inclusion. C. trachomatis modifies the inclusion membrane by type III secretion and insertion of effectors known as inclusion membrane proteins, or Incs. These Inc proteins are critical for chlamydial pathogenesis via their interactions with host proteins and their capacity to stabilize the inclusion membrane. Previous studies from our lab demonstrated the localization of two eukaryotic proteins, Flightless 1 (FLI1) and its binding partner leucine-rich repeat interacting …

Genetic Drivers And Tumor Milieu Analysis In Mantle Cell Lymphoma, Sunandini Sharma

Theses & Dissertations

Mantle Cell Lymphoma (MCL) is a B-cell lymphoma characterized by t(11;14) leading to CyclinD1 (CCND1) overexpression with highly variable clinical response. Although the tumor intrinsic mechanisms have been fairly studied, the role of the tumor microenvironment (TME) in survival and therapeutic responses is marginally examined. Herein, we integrated high-throughput genomics and characterized TME using a highly multiplexed, spatially resolved, single-cell digital pathology approach termed imaging mass cytometry (IMC) to delineate the tumor-immune landscape. We identified eight MCL genomic subtypes with distinct signatures and prognoses. Subsets C2, C5, and C6 had poorer outcomes with a 5-year overall survival (OS) of 33-50% …

Sensory Dysfunction And The Role Of Nrf2 In The Production Of Pain In Chronic Hindlimb Ischemia, Oliver Kitzerow

Theses & Dissertations

Peripheral arterial disease (PAD) is a progressive and debilitating atherothrombotic disorder that is estimated to impact >200 million people worldwide. Higher physical activity levels are associated with better overall survival rates, slower decline of functional capability, and improved quality of life. However, intermittent claudication, pain produced by physical activity, severely limits functional capacity in PAD patients. Despite known sensory dysfunction and documented neuropathy in diseased patients, the neural mechanisms that produce pain in PAD are yet to be identified. Importantly, few animal models of hindlimb ischemia (HLI) successfully recapitulate chronic human PAD. We developed a chronic animal model of HLI …

Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton

Theses & Dissertations

Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Multimodal Investigations For The Identification Of Surgically Relevant Brain Areas, Kevin Tyner

Theses & Dissertations

Epilepsy is a neurological disease leading to recurrent and unpredictable seizures. Patients can be diagnosed as focal onset, where the seizure focus resides in one hemisphere; generalized onset, where seizure foci reside in both hemispheres; or unknown onset. Anti-seizure medications are the first line of treatment, and those whose seizures cannot be controlled with medication are diagnosed with drug-resistant epilepsy (DRE). For patients diagnosed with focal onset epilepsy to achieve seizure freedom, surgical resection of the epileptogenic zone (EZ), the region of the brain that is both necessary and sufficient for initiating seizures, is required. The EZ is a theoretical …

Factors Associated With Sedentary Behavior And Physical Activity During Hospitalization For Hematopoietic Stem Cell Transplantation, Gisele C. Tlusty Phd, Rn

Theses & Dissertations

Purpose: Physical activity may decrease inactivity-related complications associated with hematopoietic stem cell transplantation (HSCT). Factors associated with objectively measured sedentary behavior and physical activity during HSCT have not been studied adequately. This study aimed to describe the clinical and personal factors associated with sedentary behavior and physical activity starting with the day of hematopoietic stem cell transplantation, for 10 days during hospitalization, and the first 7 days after discharge.

Methods: This longitudinal, observational study measured sedentary behavior and physical activity with accelerometers on HSCT days 0-4 (T1), days 5-9 (T2), and the first 7 days after hospital discharge (T3). Clinical …

Cardiovascular Disease Risk Reduction Program For Hispanics In The Us Midwest: A Culturally Adapted Intervention, Armando De Alba

Theses & Dissertations

Cardiovascular disease (CVD) represents the second leading cause of death in Nebraska (NE), accounting for approximately one in every five deaths. In the state, there are marked ethnic and rural-urban disparities in the prevalence of chronic diseases and resultant deaths. For instance, while the rates in NE of coronary heart disease and myocardial infarction between 2001 and 2010 decreased among non-Hispanic Whites, the rates for Hispanics almost tripled. There is little evidence of CVD risk factor reduction strategies being implemented in Midwestern areas and Hispanic populations.

One promising approach for reducing CVD risk involves health education and lifestyle modification programs …

Experiences Of Registered Nurses Returning To Practice After A Career Break, Jill V. Scott

Theses & Dissertations

This dissertation explores the complex experiences of Registered Nurses (RNs) returning to practice, with a particular focus on the impacts of self-efficacy, recruitment strategies, and regulatory barriers. The first article, a literature review, examines the self-efficacy of RNs returning to practice, emphasizing the importance of refresher programs and support to facilitate this transition. This review also evaluated the preparedness of RNs re-entering the workforce, and evaluated the role of self-efficacy in successful reintegration into clinical practice. The second manuscript delves into the challenges of reaching and recruiting health professionals who have left the profession, identifying community partnerships, social media, and …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Normal And Varied Morphological Structure Of The Fossa Ovalis And Its Clinical Relevance, Christian G. Valverde

Theses & Dissertations

Congenital heart defects are atop the list of the most common type of birth defects in modern obstetrics. According to the Center for Disease Control and Prevention, nearly 40,000 births each year are diagnosed with a congenital heart defect, composing an annual rate of 1%. Of those 40,000 births, roughly 1 in 4 are severe enough to require surgical intervention. Acknowledging that heart disease has been the leading cause of mortality for the past several decades, the former can certainly have additive effects toward this trend. There are several different etiologies and forms of heart defects that are often found …

Implementation Of A Validated Suicide Screening Tool In A University Student Health Center, Tessa Welniak, Bailey Coslor, Cathrin Carithers

Doctor of Nursing Practice Projects: College of Nursing

Purpose. Suicide is the second leading cause of death among adults in the United States and Nebraska. Death by suicide impacts millions of adults every year in the United States but warning signs are often missed during visits with primary care providers. The University of Nebraska at Kearney (UNK) Student Health Center (SHC), like many other primary care clinics, did not routinely screen patients for suicide risk. According to the Joint Commission, all patients over 12 years of age should be screened for suicide using a validated screening tool if the visit is for any behavioral health concern. The project’s …

Implementation Of A Doula-Supported Postpartum Wellness Toolkit In A Black Community-Based Maternal Wellness Program, Janice Luethje, Leslie Torres

Doctor of Nursing Practice Projects: College of Nursing

Objective: The objective of this project was to expand the areas of focus within a maternal wellness program at a Black community center and to evaluate the satisfaction levels of the doulas who utilized the material during postpartum home visits. The toolkit covers a range of postpartum topics in the areas of nutrition, exercise, sexual health, mindfulness, and social support as well as a postpartum mental health screening tool.

Design: This quality improvement project included three distinct phases: The pre-implementation phase, the implementation phase, and the post-implementation phase.

Setting: The project location was a Black community center in Lincoln, Nebraska. …

Implementing A Standardized Protocol For Early Detection Of Undiagnosed Hypertension Patients, Jenscena Hansen, Chris Bell

Doctor of Nursing Practice Projects: College of Nursing

Introduction: Hypertension is a preventable disease that frequently goes unrecognized and undertreated. Early diagnosis can prevent further comorbidities such as heart disease, stroke, and chronic kidney disease. Implementation of this protocol aims to decrease the number of patients with undiagnosed hypertension and increase the identification of patients with elevated blood pressure who did not have a pre-existing diagnosis of hypertension. The goal of implementing a standardized protocol would help eliminate the number of patients who go undiagnosed.

Methods: This quality improvement design had clinical staff flag patients with elevated blood pressure. Identified patients without a diagnosis of hypertension were educated …

Effects Of An Educational Evidence-Based Website To Improve Breast Health Knowledge And Self-Efficacy Of Breast Self-Examination: Interim Analysis, Mackenzie Koch, Jennifer Cera, Brooke Hancock, Elizabeth Graham

Doctor of Nursing Practice Projects: College of Nursing

Purpose and Aims

Breast disease, whether benign or malignant, encompasses a wide array of diagnoses. Breast self- examination (BSE) is a simple screening assessment that improves early recognition and diagnosis. With changes in the 2021 ACOG practice guidelines from mandatory to optional provider-performed clinical breast examinations (CBE), it is imperative for patients to possess basic breast health knowledge and accurate BSE techniques. Current standard patient education is provided via brochures or pamphlets. An educational multimedia website was created using ACOG guidelines to impart knowledge and demonstrate proper BSE techniques. Aims were to evaluate changes in participant’s (1) breast health knowledge …

Reduction Of Hospital-Acquired Pressure Injuries In The Acute Care Setting, Bailey Rasmussen, Taylor Bacon, Andrew Gross

Doctor of Nursing Practice Projects: College of Nursing

Background: Hospital-acquired pressure injuries (HAPIs) have been a longstanding problem in hospitals nationwide. HAPIs cause significant financial strain to a healthcare system and complications can be devastating to the patient.

Purpose: The purpose of this project was to implement the Standard Pressure Injury Prevention Protocol (SPIPP) 2.0 Checklist for patients in the Intensive Care Unit (ICU). The primary aim of this study was to determine if implementing the checklist would reduce the number of HAPIs.

Methods: This project took place over a four-week period at a Midwest hospital in the ICU. Data were collected via patient chart …

The Impact Of Aging On Fibroblast Gene Expression In Post-Extraction Wound Healing: A Single-Cell Rna Sequencing Study, Paula Christina Cohen Schlemmer

Theses & Dissertations

Wound healing is slower in aged patients. Immediately after tooth extraction, fibroblasts are activated to rebuild the ECM, which is later remodeled through the expression of MMPs. Gene expression may be altered in fibroblasts of aged patients leading to deficiencies in ECM deposition and the recruitment and proliferation of immune cells, resulting in a slow-healing fibrotic wound.

Using scRNA-seq, soft tissue was profiled from two healthy patients: one young and one aged at the time of tooth extraction. Two weeks post-extraction, a second soft tissue sample was harvested. Differentially expressed genes were used to identify enriched pathways for each …

Serum Antibodies To Periodontal Pathogens And Anti-Malondialdehyde-Acetaldehyde: Potential Role In The Interrelationship Between The Periodontium And Rheumatoid Arthritis, Joyce Lee

Theses & Dissertations

Objectives: Study 1 – To quantify associations between anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum serum antibody concentrations and risk of developing rheumatoid arthritis (RA). Study 2 – To test if periodontal clinical measures, alveolar bone loss (ABL), and the aforementioned serum anti-bacterial antibody concentrations are associated with anti-malondialdehyde-acetaldehyde (MAA) serum antibody concentrations.

Methods: Study 1 – Serum samples pre- and post- RA diagnosis (n=214 cases, 210 matched controls) from the U.S. Department of Defense Serum Repository were utilized to compare timing of elevations of anti-bacterial antibody concentrations relative to RA diagnosis and associations …

Examining Patient Preferences And Perceptions Of Provider Communication Strategies For Variant Reclassification In Hereditary Cancer Genetic Testing, Mitchell Mcelfresh, Katie Hutto, Gwen Reiser, Bronson Riley, Charlie King

Capstones: Genetic Counseling

Genetic testing plays a role in oncology care by providing insight into patient’s cancer risk and guiding medical management. Variants in genes are classified by their potential to cause disease according to the five-tier system recommended by the American College of Medical Genetics (ACMG). Reclassification of variants is fluid and can lead to both changes in medical management and challenging discussions. Previous research has described methods genetic counselors use for recontacting patients about reclassification, but not whether these methods align with patient preferences. This study employed a mixed methods survey for patients in Nebraska (recruited via flyer and mail) and …

Addressing Equitable Access In A Safety-Net Hospital System: An Implementation Framework, Hillary Alycon

Dissertations: Doctor of Public Health

Acute care organizations face a significant challenge in effectively implementing health equity programs, particularly in rural areas where guidance is often lacking. Despite abundant literature focusing on health outcomes, there remains a noticeable dearth of published data on implementing health equity initiatives. In response to this gap, I present a comprehensive analysis that utilizes readily available, open-sourced data to address this critical issue.

A thorough assessment of the demographic characteristics of acute care facilities within the catchment regions was conducted based on data from reputable sources such as the US Census Bureau, the American Community Survey, and the County Health …