Targeting Vulnerabilities In Cell State And Calcium Signaling For The Treatment Of Lung Cancer, Clark Jones

Graduate Theses, Dissertations, and Problem Reports

Lung cancer remains the deadliest of all cancers due to the high mutational burden associated with the disease. Combating mutational drivers and drug resistance proves to be essential in the development of novel therapies to improve patient outcomes. A first-in-class cyclic peptide known as MTI-101 has been shown to induce necrotic cell death in a caspase independent manner. MTI-101 was derived from the linear peptide known as HYD1 that was found in a high throughput screen to block cell adhesion with the extracellular matrix. The compound was further optimized and cyclized to the currently used MTI-101 that was found to …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Utilizing The K18-Hace2 Mouse Model To Develop Protective Covid-19 Vaccines, Ting Y. Wong

Graduate Theses, Dissertations, and Problem Reports

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the respiratory virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Similar to other respiratory viruses, SARS-CoV-2 is transmitted through inhalation of respiratory droplets and aerosols from infected individuals. Once inhaled, SARS-CoV-2 utilizes the receptor binding domain (RBD) on the spike protein to bind to human Angiotensin Converting Enzyme 2 (hACE2) receptor to gain entrance into host cells to begin viral replication. SARS-CoV-2 infection can result in mild to severe cases of COVID-19 ranging from asymptomatic infections, cold or flu like symptoms to respiratory failure. The onset of the pandemic in …

Preconception Substance Use And Risk Of Unintended Pregnancy, Saima Shafique

Graduate Theses, Dissertations, and Problem Reports

Background: In the United States, unintended pregnancy is a serious public health issue due to its persistent high prevalence. In the series of three studies, our first two investigations examined the risk and potential determinants of unintended pregnancy among substance and polysubstance using women of childbearing age. In the third study, we conducted a systematic review (SR) with meta-analysis (MA) to assess the association of illicit and recreational drugs to the risk of unintended pregnancy.

Methods: We performed a secondary data analysis on a subset of Pregnancy Risk Assessment Monitoring System (PRAMS) 2016-17 phase 8 data (n=75,543). The outcome variable …

Factors Associated With Service Utilization In Injured Workers In West Virginia, Brandy Brown

Graduate Theses, Dissertations, and Problem Reports

Introduction: Minimal research has been conducted on healthcare utilization among injured workers residing in rural areas. These workers are often at high risk for work-related injury due to the industries in which they work and commonly experience barriers to accessing healthcare. The first study in this dissertation series explored general characteristics of injured workers receiving care at occupational medicine clinics in West Virginia (WV). The second and third studies explored the moderating effects of rurality, pain medication, and psychiatric medication on sociodemographic and health status factors and number of medical encounters.

Methods: Each study used a cross-sectional design with data …

Experience Of Parents Caring For A Child With An Acquired Disability, Brad E. Phillips

Graduate Theses, Dissertations, and Problem Reports

Background: Parents caring for a child with an acquired disability often report a negative impact on physical, psychological, emotional, and spiritual health associated with caregiver burden related to their child’s complex health needs. This is further complicated by additional challenges related to the loss of a previously healthy child. Traditional patterns of loss follow linear, time-bound stages that have been observed to be unrelated to the experiences of these specific parents and their families. Therefore, the concept transforming loss has been developed to better understand how these parents navigate loss and find meaning in spite of their suffering.

Purpose: The …

Cbct Use In Orthodontic Residency Programs In Usa, Su Min Han

Graduate Theses, Dissertations, and Problem Reports

Background and Objectives: Cone beam computed tomography (CBCT) scans in dentistry have been up and coming forms of x-ray technology that allows cross-sectional images to form a comprehensive 3-dimensional representation of the mouth. While the typical use for CBCT imaging is reported to be for implant dentistry, there are many contexts in which it is indicated in orthodontics. There are various schools of thought regarding when CBCT is indicated for specific diagnosis of problems or general use in the collection of initial, progress and post-treatment orthodontic records. There are programs that follow the Radiology guidelines for taking CBCT scans10 and …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

Zonulin As A Mediator Of Psychological Stress And Periodontal Disease, Casey D. Wright

Graduate Theses, Dissertations, and Problem Reports

The prevalence of chronic inflammatory diseases is on the rise. Some have posited the permeability of tight junctions in gastrointestinal epithelium tissues as a potential mechanism for precipitating inflammatory processes throughout the body. Zonulin is the only known modulator of tight junction permeability and has been implicated in numerous chronic inflammatory processes (e.g., proinflammatory cytokine production) and diseases, more generally. The role of zonulin in oral inflammation, however, has yet to be explored. Periodontal disease is the most common oral inflammatory condition and primary perpetrator of tooth loss. Periodontal disease also is associated with a number of other health problems …

A Domain Adaptation Approach For Segmenting Cell Instances In Microscopy Data, Matthew R. Keaton

Graduate Theses, Dissertations, and Problem Reports

Automated cellular instance segmentation is a process that has been utilized for accelerating biological research since before the deep learning era, and recent advancements have produced higher quality results with less effort from the biologist. Most current endeavors focus on completely cutting the researcher out of the picture by generating highly generalized models. However, these models invariably fail when faced with novel data and effectively opt to miss out on the full capabilities of deep learning in pursuit of this goal. In our work, we demonstrate how, with even a minimal amount of annotated data, dominant approaches in this space …

The Process And Case Study Approach To Implementing A Nutrition-Specific Dissemination And Implementation Science Training In Appalachia, Ayron E. Walker

Graduate Theses, Dissertations, and Problem Reports

Introduction: Nutrition professionals face implementation challenges due to their lack of knowledge to incorporate D&I science into intervention design. To improve intervention outcomes, nutrition professionals must be trained in D&I science, which are currently absent in the field.

Aims: To identify and assess nutrition educators and practitioners perceived motivations, self-efficacy, and attitudes in using D&I science to inform the educational design and strategies of a nutrition-specific D&I curriculum for nutrition educators. Then to test feasibility of the nutrition-specific curriculum in increasing knowledge, self-efficacy, and attitudes by a case study approach, pre/post intervention design.

Methods: First, scoping review methodology involved the …

Raising Awareness Of Second Victim Phenomenon And Supportingyou: A Quality And Safety Initiative, Megan Renee Bryant

Graduate Theses, Dissertations, and Problem Reports

Current literature has established a need for practice change in management of healthcare-related critical incidents. Peer-support programs have been cited as the most impactful resource healthcare professionals request following a critical incident (Daniels & McCorkle, 2016). SupportingYOU, a peer-support program, is in the process of expansion at a large academic children’s hospital in northern West Virginia in anticipation for the opening of a new facility. The specific aim of this project was to raise awareness of second victim phenomenon (SVP), SupportingYOU, and perception of awareness of resiliency. Interventions included multi-formatted educational sessions on SVP and SupportingYOU via PowerPoints, brochures, flyers, …

Autonomous And Non-Autonomous Requirements For The C-Jun N-Terminal Kinase Signaling Pathway In Early Forebrain Development, Jessica G. Cunningham

Graduate Theses, Dissertations, and Problem Reports

The cerebral cortex is responsible for a wide variety of high-level functions including cognition, sensory perception, fine motor control, and the orchestration of body movements. The cortex is comprised of cortical excitatory neurons and inhibitory interneurons, which are arranged in a highly organized fashion into different layers and regions. These two types of cells operate in a delicate balance between excitation and inhibition, which is critical for proper cortical circuitry. In order for the cortex to execute its numerous functions, it must both send and receive input to other brain regions through axonal connections. The organization within the cortex and …

A Preoperative Intervention To Improve Glycemic Control In Surgical Patients With Diabetes, Kelsey L. Boyd

Graduate Theses, Dissertations, and Problem Reports

Perioperative hyperglycemia is reported in 20-40% of patients undergoing general surgery and is an independent risk factor for negative surgical outcomes. Patients with diabetes presenting to a local community hospital are at risk for negative surgical outcomes due to the lack of strategies to prevent perioperative hyperglycemia. This project aimed to implement and evaluate the usefulness of succinct diabetes education for preoperative total joint surgical patients with diabetes. The intervention was a nurse-led, face-to-face diabetes education session provided to total joint surgical patients with diabetes during a preoperative evaluation appointment, compared to usual care (no preoperative diabetes education). This project …

Monitoring The Systemic Immune System To Understand And Improve The Efficacy Of Immunotherapy For Metastatic Osteosarcoma, Justin Edward Markel

Graduate Theses, Dissertations, and Problem Reports

Osteosarcoma (OS) is a complex tumor with no effective targeted therapies due to its genomic heterogeneity and pleomorphism. The immune response it creates, particularly against metastatic lesions, is considerable; however, various suppressive mechanisms induced by the tumor prohibit its effectiveness. The presence of infiltrating lymphocytes suggests that therapeutic disinhibition through checkpoint blockade could increase antitumor immunity, though none have been successful in clinical trials. The complexities of the immune response to OS tumors have yet to be unraveled; however, there is evidence to suggest that cell-mediated immunity (CMI, specifically T cells, Natural Killer [NK] cells, and myeloid-lineage cells [MLCs]) plays …

Implementing Trauma-Informed Care Through A Multi-Agency Learning Collaborative: A Theory-Driven Analysis Of Outcomes And Sustainability, Mira D H Snider M.S.

Graduate Theses, Dissertations, and Problem Reports

Learning collaboratives (LCs) are often used in large-scale implementation initiatives to promote evidence-based practice across provider networks. Although the outcomes and stakeholder perspectives of many LCs have been documented, support for the effectiveness of LCs is equivocal, and the means by which LCs achieve long-term improvements in clinical care are not understood. The current study investigated outcomes and sustainability of a multi-agency LC for implementing trauma-informed care in 23 rural Pennsylvania counties. Changes in outcomes (i.e., trauma symptom screening, trauma-informed care training attendance, clinician confidence with using trauma informed-care, utilization of trauma-related diagnostic codes, retention in service, service unit density) …

Knowledge And Training In Language Sample Analysis Of Us Speech-Language Pathology Graduate Students, Allegra Cornaglia

Graduate Theses, Dissertations, and Problem Reports

Purpose: Speech-language pathologists (SLPs) play an integral role in identification and treatment of developmental language disorders (DLD). Best practices include the use of language sample analysis (LSA) as part of a comprehensive evaluation. However, LSA requires a specific set of foundational morphological and syntactic knowledge. Previous studies have shown a knowledge gap for both SLPs and SLP graduate students for other areas of morphosyntax and phonology. This study examined the language analysis skills of current SLP graduate students on a test of Mean Length of Utterance (MLU) analysis and Clausal Density (CD) and whether there were possible factors associated with …

Passive Self-Ligating Brackets Vs. Conventional Brackets: Is There A Difference In The Transverse Dimension? A Systematic Review And Meta-Analysis, Justin Scott Tenbrook

Graduate Theses, Dissertations, and Problem Reports

Background and Objectives:

Self-ligating brackets have risen in popularity in clinical orthodontics, but many claims made by their manufacturers have been made without substantial evidence. Any differences among the bracket types are very small when consulting new peer reviewed literature testing their differences. Nevertheless, self-ligating brackets are still purported to be able to increase the dental transverse dimension more effectively than conventional brackets. In 2018, Yang et al. performed a systematic review on the transversal changes, space closure, and efficiency of conventional and self-ligating appliances. Since then, there were several clinical trials published in the literature comparing the mandibular arch …

Immediate Loading Of 4 Guided Implants Supporting A Maxillary Overdenture Using A Novaloc Retention System, Doheum Choi

Graduate Theses, Dissertations, and Problem Reports

The purpose of this study was to test the treatment concept of maxillary overdenture retained by four unsplinted implants placed using a flapless guided approach and immediate loading with Novaloc® attachments. Subjects with fully edentulous maxillae received 4 BLX implants (Roxolid®, SLActive®, 3.75mm diameter, Institut Straumann AG, Basel, Switzerland) to support an immediately loaded overdenture. Implants were connected with Novaloc® attachments (Institut Straumann AG, Basel, Switzerland) immediately following surgery if insertion torque (IT) reached 20 N/cm or above. The primary outcome variable was the radiographic bone level change at 6- and 12-months following implant placement. Secondary outcome variables were peri-implant …

Survival Rate Of Dental Implants Placed In Alveolar Ridge Preservation Sites - Systematic Review, Sravanthi Papisetti

Graduate Theses, Dissertations, and Problem Reports

Introduction: It is not known so far performing Alveolar Ridge Preservation (ARP) in a freshly extracted socket with intact walls would improve clinical outcomes of implants placed in these sites. It is not known whether different biomaterials and techniques would affect the survival of dental implants.

Aim: The current systematic review is undertaken to assess the survival rate of dental implants placed in these sockets and to assess different socket graft materials as well as techniques of ridge preservation with regard to the survival of implants.

Material methods: Search for relevant articles was done in Medline (PubMed). No …

Implementation Of Stress Management And Resiliency Training To Address Nursing Burnout In A Neuroscience Critical Care Unit, Jessica May Marie Hughes

Graduate Theses, Dissertations, and Problem Reports

In the United States, over one-third of nurses experience symptoms of burnout (Reith, 2018). If left unchecked, poor stress management and resiliency skills can contribute to nursing burnout, leading to costly employee turnover. Stress management and resiliency training (SMART) provides the tools necessary to develop resiliency, improve stress management and decrease burnout (Resilient Option, 2020). Nursing staff under the age of 36, who work in a Neurosciences Critical Care Unit (NCCU) demonstrate lower resiliency scores and a higher risk of burnout. This project aimed to evaluate: (a) the effects of a SMART program on the wellbeing of nursing staff in …

Accuracy, Prosthetic Outcomes, And Patient-Related Outcomes With Immediate Loading Of 4-Guided Implants Supporting An Unsplinted Maxillary Implant-Retained Overdenture, Nathaniel Chertok

Graduate Theses, Dissertations, and Problem Reports

Aim: Assess the accuracy of implant placement using a mucosa-supported surgical guide relative to the planned implant position and examine patient-related outcomes associated with immediately-loaded Mx IOD using a single-attachment abutment system. The secondary aim of the study is to examine the prosthetic complications associated with this treatment.

Materials and methods: Fifteen individuals with edentulous maxillae were included. Each participant received 4 Straumann BLX implants through a stereolithic mucosa-supported surgical guide distributed in the Mx arch to maximize AP spread. Implant lengths ranged from 10 to 14 mm. A post-op CBCT was taken after the surgery to compare …

The Effect Of A Standardized Handoff Tool On Communication, Interunit Transitions, And Wait Time: A Quality Improvement Project, Silvia N. Myndresku

Graduate Theses, Dissertations, and Problem Reports

This project sought not only to improve the communication and interunit transitions of care between emergency department providers (EDPs) and inpatient providers (IPs) using a standardized handoff tool, but also to reduce the Emergency Room (ED) wait time for patients admitted to the community hospital. The project employed a quantitative quasi-experimental pre-test/post-test design to explore provider satisfaction with an evidence-based standardized handoff tools and wait time. Forty-eight providers completed the survey before the I-PASS implementation, and 43 providers completed the survey post I-PASS implementation. Though not statistically significant, data indicates that wait time increased for the post-implementation months of December, …

Screen Media Use Among Children And Adolescents – Applications Of Supervised And Unsupervised Machine Learning And Sentiment Analysis, Yifan Zhang

Graduate Theses, Dissertations, and Problem Reports

Screen media has become increasingly pervasive in our everyday lives and has profoundly changed the way people communicate and interact with each other. However, we are still unclear about the long-term influence of screen media use on our physical health, mental health, and social wellbeing. Children and adolescents are in an important stage of brain development and are susceptible to the environmental influence that screen media possess. This dissertation pursued three aims to address research gaps related to screen media use among children and adolescents: 1) identify topics and knowledge gaps in screen media use research among children and adolescents …

Examining The Efficacy Of A Self-Paced Online Training For Goal Writing, Allison Rosborough

Graduate Theses, Dissertations, and Problem Reports

Educational goals can control critical aspects of intervention and progress monitoring for students with disabilities and as such are a central feature of Individualized Education Programs (IEPs). Despite its importance, school staff frequently report not receiving enough training or support on IEP documentation. Rosborough and Brandel (2020) investigated the quality of IEP goals written in the state of West Virginia. Findings indicated that professional development activities needed to be designed and analyzed related to immediate and long-term efficacy. The purpose of this study was to evaluate the efficacy of a self-paced, online training for goal writing. Participants were recruited by …

Low- And High-Wattage Vaping During Pregnancy Influence Aortic Structure And Function In Rat Offspring, James Ian Frazier

Graduate Theses, Dissertations, and Problem Reports

Introduction: Electronic cigarettes (e-cigs) are being marketed as a healthier alternative to traditional cigarettes, yet the health consequences of e-cig usage (also called vaping) are still being investigated. E-cigs are easily customized for user preferences. For example, the choice of flavors, nicotine concentration, and/or the temperature (i.e., wattage) used to heat the e-liquid can be selected in many devices. Emerging evidence suggests that vaping during pregnancy impairs cerebral vascular function in rodent offspring. In this study, we sought to investigate the potential effects of changes to e-cig device wattage (i.e., 5W vs. 30W) with maternal vaping during pregnancy on vascular …

Evaluation Of A Comprehensive Diabetes Mellitus Protocol At A Rural, Federally Qualified Health Center In Southern West Virginia, Hannah D. Davis

Graduate Theses, Dissertations, and Problem Reports

Background: Diabetes mellitus is a chronic disease that affects nearly 34 million Americans. In rural Appalachia, the population is affected disproportionately at a rate of 14% compared to the national average of 10%. Diabetes is a lifelong, chronic condition managed best by a multidisciplinary team-based approach to achieve optimal disease control. Best practices in the care of diabetes support the use of evidenced based care protocols and leveraging technology to decrease the burden of disease. Type 2 diabetes mellitus (T2DM) is the most common type, making it the focal population for evaluation.

Purpose: The purpose of this project was to …

Standardized Postoperative Handoff Tool To Improve Handoff Quality, Haley Durkacz

Graduate Theses, Dissertations, and Problem Reports

Abstract

Effective communication between healthcare providers is an essential element in the delivery of safe patient care. Loss of relevant information can occur during all phases of patient care but is most inclined to occur during the handoff from the operating room to the postoperative anesthesia care unit (PACU). Evidence has indicated that the transfer of patients by anesthesia providers remains informal and brief despite practice guidelines. When pertinent details are omitted during the anesthesia handoff there is a potential increase for medical errors, delayed treatment, and patient harm. The purpose of this project was to analyze the use of …

A Quality Improvement Initiative Regarding Ondansetron In The Prevention Of Spinal Anesthesia-Induced Hypotension, Kassidy Dell Nutter

Graduate Theses, Dissertations, and Problem Reports

Spinal anesthesia is an excellent choice as the primary anesthetic for lower abdominal, perineal, and lower extremity procedures. Spinal anesthesia boasts several distinct advantages over general anesthesia. However, it is important to note that spinal anesthesia does not come without risk. The most common adverse reaction of spinal anesthesia is hypotension. Anesthesia providers use several methods to combat the hypotension that is so commonly associated with spinal anesthesia. One emerging trend to prevent spinal anesthesia-induced hypotension (SAIH) is the administration of ondansetron, a serotonin 5-hydroxytryptamine3 antagonist. Evidence has shown that the administration of ondansetron just prior to spinal anesthesia administration …

A Quality Improvement Initiative For Intraoperative Low Dose Ketamine Utilization In Thoracotomy, Jason Wampler

Graduate Theses, Dissertations, and Problem Reports

The challenge of postoperative pain control following a thoracotomy is well noted among anesthesia providers. The intraoperative utilization of low-dose ketamine in several patient populations, including those undergoing a thoracotomy, has been deemed a viable intervention in the multi-modal analgesia plan at not only reducing postoperative pain scores for patients, but also reducing opioid consumption. This quality improvement project sought to increase provider awareness of this intervention among anesthesia providers in a community hospital with a goal to influence a practice change. This was completed using a pre-post design centered around an educational in-service, with an additional 60-day follow-up survey …