Digital Commons Network^™

Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee

Dissertations and Theses (Open Access)

Patients with BRAF^V600E-mutated metastatic colorectal cancer (mCRC) experience a worse prognosis and demonstrate only a 5% response rate to BRAF inhibitor treatment. In this study, adaptive resistance, and a potential combination of standard therapies in BRAF^V600E CRC were unveiled. Intriguingly, a robust association of BRAF^V600E mutation and DNA hypermethylation suggests this is a unique subgroup harboring aberrant epigenetic phenotype. Firstly, DNA methyltransferase (DNMT) inhibitor treatment induced profound DNA hypomethylation in vivo, but minimal change in gene expression due to adaptive elevation of the repressive histone methylation, H3K27me3, leading to compensatory suppression of key tumor suppressor genes, …

Patient Preferences For Ultrasound Soft Sign Disclosure With Prior Negative Cfdna Screening, Disha Patel

Dissertations and Theses (Open Access)

Soft signs are nonstructural fetal anomalies that can be identified by the second-trimester comprehensive ultrasound examination. In isolation, soft signs are insufficient to diagnose chromosome conditions but can adjust an individual's risk for aneuploidy, primarily Down syndrome. In the age of noninvasive cell-free DNA (cfDNA) prenatal screening, which exhibits superior sensitivity and specificity for aneuploidy compared to what can be provided by soft sign risk adjustment, the utility of these soft signs is arguably waning. Thus, this study aimed to establish patient preferences for whether and how soft signs are disclosed in pregnancy to inform recommendations for disclosure. A survey …

Influential Factors For Disclosing A Tuberous Sclerosis Complex Diagnosis To Romantic Partners, Laura Gorecki

Dissertations and Theses (Open Access)

Tuberous sclerosis complex (TSC) is a highly variable genetic condition characterized by multi-organ tumor predisposition. Due to the heritability, variability, and severity of this condition, individuals with TSC may face unique psychosocial challenges in dating and romantic relationships, specifically related to disclosing their diagnosis to romantic partners. Despite disclosure within romantic relationships being explored in the context of other genetic conditions, this area has not yet been explored in the TSC community who face unique challenges related to physical and mental health, educational performance, and overall quality of life. This study surveyed 117 independent adults with TSC regarding the following …

Efficacy Of Genetic Testing Methodologies For Prenatal Detection Of Skeletal Anomalies And Craniosynostosis Syndromes, Nicolette Murphey

Dissertations and Theses (Open Access)

Prenatal ultrasound findings suggestive of skeletal dysplasia often have a wide differential with over 450 skeletal dysplasia syndromes described to date. Specific phenotypic features on ultrasound provide guidance, though we noted in this study that molecular testing is most informative in making a diagnosis. Prenatal genetic testing ranges from screening tests using cell-free fetal DNA to diagnostic tests which include next generation sequencing panels and whole exome or genome sequencing. We aimed to determine which prenatal genetic tests were capable of identifying disease causing variants in pregnancies suspected to have skeletal dysplasia and craniosynostosis syndromes. This multi-center retrospective chart review …

Mapping The Neural Circuits That Underlie Metabolic Vs. Emotional Regulation Of Food-Seeking Behavior, Xu Zhang

Dissertations and Theses (Open Access)

Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food …

Dysmorphology Training And Utility In Genetic Counseling, Maria G. Hernandez

Dissertations and Theses (Open Access)

Before the availability of comprehensive genetic testing, dysmorphology was critical for developing a differential for individuals suspected of having a genetic disorder. Literature suggests that the availability of whole exome and whole genome sequencing (ES/GS) has shifted the use of dysmorphology from a forward to backward approach. There is no literature describing the continued use of dysmorphology within the genetic counseling field or the training that genetic counseling students receive. The study aims to describe the dysmorphology training that genetic counselors (GC) and GC students reported receiving, to explore the involvement of GCs in evaluating dysmorphic features and identify factors …

Inclusion Of Adoption As A Pregnancy Management Option In Prenatal Genetic Counseling Practice, Emma Billings

Dissertations and Theses (Open Access)

Prenatal genetic counselors are essential to providing education, psychosocial support, and guidance on pregnancy options to patients who receive a fetal diagnosis of an anomaly or genetic condition. Therefore, genetic counselors should be well-educated on comprehensive pregnancy management options consisting of parenting, abortion, and adoption. The landscape of adoption education in genetic counseling practice was last characterized in 2010 by Perry and Henry, revealing substantial variability in both the inclusion of adoption-specific education in genetic counseling program (GCP) curricula and the discussion of pregnancy options with patients in prenatal practice. As a result, the authors published a call to action …

Fraud In Genetic Testing: Swindling The System, Rachel Notestine, Rachel Notestine, Claire N. Singletary

Dissertations and Theses (Open Access)

Healthcare fraud comprises a sizable portion of the United States healthcare expenditure and inflicts strain on payors, patients, and the healthcare system overall. The genetic testing industry is rapidly growing which provides a multitude of fraud opportunities. There is limited research exploring genetic testing fraud, although federal organizations have highlighted it as an issue. In this study, a retrospective review of federal websites, news articles, and a legal database identified 42 cases of fraud involving outpatient genetic testing published between February 2019 and December 2023. These cases were analyzed for themes via inductive conventional content analysis. Themes of fraudulent activity …

Methods For The Prediction Of Osteoradionecrosis Resulting From Head And Neck Cancer Radiation Therapy, Brandon Reber

Dissertations and Theses (Open Access)

Head and neck cancer (HNC) is the sixth most diagnosed cancer worldwide with over 600,000 patients diagnosed every year. One of the primary methods to treat HNC is through radiation therapy (RT). While RT is effective at treating HNC, late toxicities resulting from treatment can occur months to years post-treatment and can cause debilitating quality of life changes for HNC survivors. One of these late toxicities is osteoradionecrosis (ORN), which is the death of bone due to radiation. For HNC, the mandible is commonly affected and can cause challenges chewing, swallowing, and physical appearance changes. Several factors indicate the pressing …

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …

Dysmorphology Training And Utility In Genetic Counseling, Maria Hernandez, Maria Hernandez

Dissertations and Theses (Open Access)

Before the availability of comprehensive genetic testing, dysmorphology was critical for developing a differential for individuals suspected of having a genetic disorder. Literature suggests that the availability of whole exome and whole genome sequencing (ES/GS) has shifted the use of dysmorphology from a forward to backward approach. There is no literature describing the continued use of dysmorphology within the genetic counseling field or the training that genetic counseling students receive. The study aims to describe the dysmorphology training that genetic counselors (GC) and GC students reported receiving, to explore the involvement of GCs in evaluating dysmorphic features and identify factors …

Impact Of Genetic Counseling On Patient Empowerment After Diagnosis Of Fetal Anomaly, Carley Brueckner

Dissertations and Theses (Open Access)

Approximately 3-5% of pregnancies are affected by fetal anomalies, often leading to structural and functional differences that impact infant health and mortality. When anomalies are identified on prenatal ultrasound, genetic counseling (GC) and genetic testing may be offered to investigate the potential for a possible syndromic cause. Genetic counselors provide education on the chance for a genetic etiology, available testing options, potential changes in medical intervention related to an identified etiology, and psychosocial counseling and resources. Regardless of a patient’s testing decision, genetic counseling should include psychosocial counseling to support and empower patients in a time of prognostic uncertainty and …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Interrogating Therapeutic Resistance To Oncogenic Krasg12c-Based Therapies In Colorectal Cancer, Oluwadara Coker

Dissertations and Theses (Open Access)

Colorectal cancer is the second leading cause of cancer-related deaths and the third most common cancer in the United States. Although KRAS is mutated in 50% of patients with metastatic CRC (mCRC), it has historically been a challenging therapeutic target. The recent approval of novel covalent inhibitors selective for KRASG12C mutation have entered the clinic, which has not only marked a major milestone in cancer drug discovery but has also intensified efforts to directly target other KRAS mutations that have also successfully entered the clinic. However, treatment-associated resistance mechanisms have long threatened to attenuate clinical benefit through either adaptive or …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Molecular Basis Of Cell Membrane Adaption Against Daptomycin In Enterococcus Faecalis, April Nguyen

Dissertations and Theses (Open Access)

Daptomycin is a last-resort lipopeptide antibiotic that disrupts cell membrane (CM) and peptidoglycan homeostasis (Grein et al., 2020a; Müller et al., 2016a). Enterococcus faecalis has developed a sophisticated mechanism to avoid daptomycin killing by redistributing CM anionic phospholipids away from the septum. The CM changes are orchestrated by a three-component regulatory system, designated LiaFSR, with a possible contribution of cardiolipin synthase (Cls) (Cesar A Arias et al., 2011a; Khan et al., 2019b; Palmer et al., 2011a; Panesso et al., 2015a; Reyes et al., 2015a). However, the mechanism by which LiaFSR controls the cell membrane response and the role of Cls …

Dissecting The Relationship Between Mucin 5ac And The Lung/Gut Microbiome In The Pathogenesis Of K-Ras Mutant Lung Cancer, Maria T. Grimaldo

Dissertations and Theses (Open Access)

Non-small cell lung cancer, including its most common subtype, lung adenocarcinoma (LUAD), is the leading cause of cancer-related deaths worldwide. In LUAD patients, KRAS mutations are the most common oncogenic driver alteration. Given KRAS is upstream to many signaling pathways involved in cell survival and cytokine production, interventions against KRAS-mutant lung cancers are prone to develop acquired resistance. Thus, there is a need to develop alternate targeting strategies and test combination therapies for improved intervention. Previously, we have found that KRAS-mutant LUAD (KM-LUAD) patients whose tumors harbor high expression of Mucin 5 AC (MUC5AC), a main airway secretory mucin, have …

Development Of Systems For Processing And Managing Donations For The William A. Burnard Warming Center, Landon Corbett

Undergraduate Honors Capstone Projects

Structure is important for any organization to have success and grow. Thus, having a good inventory system can make a huge difference. This project set out to investigate and develop a system that would be able to monitor incoming donations, inventory levels, and items given away to guests. The inventory method needed to be as automated as possible because the warming center volunteers were already busy with other responsibilities.

While many softwares were researched, my proposed solution was created with a combination of Google Sheets and Google Forms, as it is free and can be customized to the specific needs …

Frontmatter (Volume 44, Issue 4), Paul B. Mojzes

Occasional Papers on Religion in Eastern Europe

No abstract provided.

Does Contingent Reward Leadership Enhance Or Diminish Team Creativity? It Depends On Leader (Un-) Predictability, Debjani Ghosh, Martin Buss, Amita Shivhare

Management Faculty Publications

Although prior research has shown that reward provision might sometimes increase creativity, little is known about how leadership that clarifies effort-reward contingencies (i.e., contingent reward leadership) is related to team creativity. Drawing on the theory of learned industriousness, we argue that contingent reward leadership can enhance team knowledge exchange and, in turn, team creative performance. However, we propose that this relationship is moderated by leader unpredictability, which can create uncertainty about resource allocation, thereby undermining the otherwise positive effect of contingent reward leadership. In a two-source, lagged design (three-wave) field study with data from 60 organizational teams, we found a …

Robo-Advisers And Investor Behavior, Benjamin Loos, Pengfei Ma, Alessandro Previtero, Andres Hackethal

Sim Kee Boon Institute for Financial Economics

Using data from a large German retail bank, we investigate the effects of the introduction of a robo-advisory tool on clients’ portfolios. Robo clients experience a significant increase in financial risk-taking and improve portfolio efficiency along several dimensions (more diversification, less home bias, more investment in passive funds, reduced investment fees). Our evidence is consistent with robo-advisers being a more cost-effective approach for offering financial advice, especially to less sophisticated investors.

Meta-Analytic Investigations Of Team Development Interventions And Effectiveness, Sydney Begerowski

All Dissertations

Team development interventions (TDIs) are evidenced-based best practices that improve performance trajectories of teams. To date, various independent studies have demonstrated the effectiveness of one type of TDI in improving effectiveness, but there has yet to be a cross-intervention assessment. Accordingly, the goal of this dissertation was to explore a subset of TDIs (team charters, team training, team debriefing) from a comparative lens. First, I conducted a series of pairwise meta-analyses across team charters, team training, and team debriefing to establish a TDI-effectiveness relationship. Findings were inconclusive regarding team charters, but suggested that team training and team debriefing significantly improve …

Phylogenetics And Biogeography Of Appalachian Trechus (Coleoptera: Carabidae), Patricia Wooden

All Dissertations

Insects have long been used as tools for understanding the health of the natural world and how changes to climate, landscape, and human interaction have affected the communities those environments support. The Appalachian Mountains, located in eastern North America, is the oldest mountain range on the continent, and during its lifespan it has supported an abundance of microhabitats and endemic species to fill them. Conservationists must balance the need to preserve the diversity that is known and continue to explore the region for new taxa, often with limited budget and expertise. A genus of small carabids, Trechus Clairville, may aid …

Reinforcement Learning-Based Energy Management For Electric Vehicle Application, Yiming Ye

All Dissertations

The increasing concerns about transportation pollution and fossil fuel depletion motivate many studies on vehicle electrification and advanced energy-saving propulsion systems. When Comparing with traditional internal combustion engine vehicles, electrified vehicles, such as battery and supercapacitor electric vehicles, are equipped with more than one power source in the hybrid propulsion system, which can save more energy through efficient power combinations. Lithium-ion batteries are the preferred choice for energy storage in electric vehicles due to their superior energy density and cost-effectiveness. Nevertheless, matching the required power input and output leads to in an unwanted growth in the size of the battery, …

Examining Policy Diffusion Mechanisms In The Contemporary Local Government Landscape Of A Politically Polarized United States, Jacob Mccauley

All Dissertations

This dissertation explores the nuanced relationship between political polarization and policy diffusion within local governments in the United States, a topic of considerable relevance given the country’s increasing political divide. By examining the diffusion of COVID-19 policies, historical marker modifications, and the implementation of eGovernment services, this research identifies a novel mechanism of policy diffusion that is significantly influenced by political party lines. The study employs a comprehensive methodological approach, incorporating case studies and quantitative analysis to examine policy implementation across politically diverse local governments. The findings reveal that political affiliation profoundly impacts policy choices, with distinct patterns of policy …

A Rhetorical-Sociological Understanding Of Emotion, Amy Boone

All Dissertations

This project presents a rhetorical-sociological understanding of emotion while foregrounding the place and role of language. Born from Sara Ahmed’s work in The Cultural Politics of Emotion, it presents a simplified equation (contact + orientation = emotion) as both a prescriptive and descriptive formula for making sense of human emotional experience. Starting with an exploration of the difficult-to-understand affect system, this dissertation identifies both rhetoric and affect as energies which cannot be understood apart from their traces, the things they move, produce, and become. As a way to get at these often-invisible forces, two trace studies are conducted which explore …

Exploring Novel Nutrient Acquisition Mechanisms For Maintaining Energy Metabolism In Toxoplasma Gondii, Melanie Key

All Dissertations

Toxoplasma gondii is an infectious intracellular parasite that establishes infection within various mammalian hosts, including humans. Toxoplasma infects approximately one-third of the global population, making it an impactful pathogen of study. T. gondii is the causative agent of toxoplasmosis, an opportunistic infection that causes severe illness or fatality in immunocompromised individuals or pregnant women. The parasite possesses a very effective invasion strategy, allowing it to cross different tissue types to disseminate infection across the placental and blood-brain barrier. Although there are a few treatments for acute toxoplasmosis, these drugs can produce adverse side effects. These options are not effective against …

An Exploration Of The Efficacy Of Virtual Agents Within Smartphone Mental Health Applications, Stephanie Six

All Dissertations

The prevalence of depression in the U.S. has increased over the past decade, leading to an all-time-high during the COVID-19 pandemic (WHO, 2022). With this increase, the number of mental health applications (MHealth apps) on virtual e-stores increases in tandem. Despite this expanding number of MHealth apps, few demonstrate a foundation in empirical research. One design factor that may influence usability and effectiveness is the inclusion of virtual agents. Three studies were conducted to investigate users’ preferences for a variety of characteristics associated with virtual agents. In Experiment 1, users completed a single-session, three-stage CBT-based interaction with virtual characters and …

Experiences Of Vertical Transfer Students In The Department Of Biological Sciences With The Transfer Credit Process: A Phenomenological Study, Laura Love

All Dissertations

The purpose of this interpretive phenomenological study was to highlight the experiences of undergraduate STEM vertical transfer students. Through the lens of Schlossberg’s Transition Theory, this study sought to better understand how students make sense of the transfer credit process and which support structures facilitated their understanding. Semi-structured interviews were conducted using qualitative methods with eight biological sciences and vertical transfer students currently enrolled at a large public four-year land-grant research institution in the Southeast United States. All participants had successfully transferred from one of 16 technical colleges within the state. Using interpretative phenomenological analysis, three themes were identified. This …

Design And Application Of Smart Systems To Address Analytical Problems, Lucas B. Ayres

All Dissertations

This dissertation is a multidisciplinary effort that integrates low-cost analytical instrumentation, redox chemistry, and artificial intelligence to overcome existing limitations in the fields of wearable sensing technology, Deep Eutectic Solvents (DES), and antioxidant chemistry. The overall goal behind each implemented strategy is to enhance the accuracy, efficiency, and accessibility of analytical processes and technologies. A general overview of the thesis, along with the research outcomes is included in Chapter One. The theoretical framework of this dissertation is presented in Chapter Two. Chapter Three describes the development of a wearable platform (sensor and instrumentation) to rapidly detect (~20 minutes) S. aureus …