Digital Commons Network^™

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …

Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden

Markey Cancer Center Faculty Publications

Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.

Methods To identify the potential markers of SkM‑derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, …

Impact Of The Affordable Care Act On Providing Equitable Healthcare Access For Ibd In The Kentucky Appalachian Region, Jennifer T. Castle, Brittany Levy, Anthony A. Mangino, Hannah G. Mcdonald, Erin E. Mcatee, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Markey Cancer Center Faculty Publications

BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown.

OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area.

DESIGN: This study was a retrospective, descriptive, and ecological study.

SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database.

PATIENTS: All encounters for IBD care for 2009–2020 for patients from the Eastern Kentucky Appalachian region were …

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …

Application Of Adversarial Attacks On Malware Detection Models, Vaishnavi Nagireddy

Master's Projects

Malware detection is vital as it ensures that a computer is safe from any kind of malicious software that puts users at risk. Too many variants of these malicious software are being introduced everyday at increased speed. Thus, to guarantee security of computer systems, huge advancements in the field of malware detection are made and one such approach is to use machine learning for malware detection. Even though machine learning is very powerful, it is prone to adversarial attacks. In this project, we will try to apply adversarial attacks on malware detection models. To perform these attacks, fake samples that …

Nitrogen Behavior In A No-Tillage Agroecosystem Located In The Inner Bluegrass Of Kentucky, Alec William Besinger Mr.

Theses and Dissertations--Plant and Soil Sciences

Nitrogen (N) is a crucial element, often limiting productivity in ecosystems. This limitation is relieved N fertilizer additions. No-tillage (NT) agroecosystems are prone to lower N availability translating to lower crop yields. The default explanation for lower N availability in NT is microbial immobilization of added N fertilizer. Historically, N availability is often assessed using chemical extractions such as KCl to evaluate levels of inorganic N in the soil. The possibility of this abiotic clay mineral fixation as mechanism in well-drained NT soils has been overlooked. The objectives of this study are to quantify N availability using KCl, NaCl, and …

The Under-Enforcement Of Crimes Against Black Women, Lisa Avalos

Journal Articles

It is well known that over-policing has a severe adverse impact on communities of color. What is less well known is that over-policing is accompanied by a corollary—a pervasive and systemic under-policing of violence against women of color. The refusal to see women of color as victims of crime who are worthy recipients of justice, and to minimize the severity of violence committed against them, are habits that are deeply embedded in the American system of [in]justice. From an 1855 Supreme Court decision refusing to recognize a female slave’s right to sexual autonomy to a prosecutor’s 2021 decision to prosecute …

Improving Early Identification Of Sepsis And Compliance Of The Core Measures In The Elderly Population, Katelyn Hood

Doctor of Nursing Practice (DNP)

Sepsis is defined as a life-threatening condition that occurs when the body’s immune system is overwhelmed by infection. This can lead to tissue damage, organ failure, and death with the most vulnerable population being those who are 65 years or older, have chronic comorbidities, have recent hospitalization, are immunocompromised, and have had a previous sepsis diagnosis. In diagnosing and treating sepsis promptly, clinical outcomes can be improved and limit the delay in diagnosis and treatment implementation. The purpose of this Doctor of Nursing Practice project was to use evidence-based practice to implement the Surviving Sepsis Campaign screening tool for patients …

Interlink Between The Gut Microbiota And Inflammation In The Context Of Oxidative Stress In Alzheimer’S Disease Progression, Tushar K Das, Bhanu P Ganesh

Faculty, Staff and Student Publications

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability and break the blood-brain barrier which may trigger AD pathogenesis via redox signaling, neuronal, immune, and metabolic pathways. Dysbiosis increases the oxidative stress. Oxidants affect the innate immune system through recognizing microbial-derived pathogens by Toll-like receptors and initiating the inflammatory process. Most of the gut microbiome research work highlights the relationship between the gut microbiota and AD, but the contributory connection between precise bacteria and brain dysfunction in AD pathology …

Is Patient Controlled Analgesia A Feasible Method Of Pain Relief In The Emergency Department: A Mixed Method Study, Raja Natasya Raja Azlan

Theses

Although pain is the most common reason for patients to present to emergency departments (EDs), conventional methods of pain management in EDs are suboptimal. Patient controlled analgesia (PCA), commonly used for post operative pain relief, was proposed as a modality of pain management in ED. PCA enables the patient to self-administer intravenous analgesia, has been rigorously evaluated in acute care settings and is widely used in many clinical areas. It is not routinely used in EDs. The literature review found critical gaps in the existing evidence of PCA use in EDs justifying this research. A three-phase sequential mixed methods study …

The Relationship Between Systems Thinking By Building Leaders And Academic Outcomes For Marginalized Students, Dunham Obadiah

Education Dissertations

Despite the attempts by lawmakers to legislate a closing of the achievement gap, persistent gaps in performance for students based on ethnicity, race, economic level, disability, and first language persist throughout public schools in the United States. Occasionally, a principal will receive attention for raising the performance of minoritized groups in their school. However, while admired, the principal’s efforts are not easily replicated. Furthermore, principal development programs fail to produce building leaders that can reliably achieve the change marginalized communities need.

There have been numerous studies that have shown that principals impact the academic performance of their students. For the …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

A Phase Change Memory And Dram Based Framework For Energy-Efficient And High-Speed In-Memory Stochastic Computing, Supreeth Mysore

Theses and Dissertations--Electrical and Computer Engineering

Convolutional Neural Networks (CNNs) have proven to be highly effective in various fields related to Artificial Intelligence (AI) and Machine Learning (ML). However, the significant computational and memory requirements of CNNs make their processing highly compute and memory-intensive. In particular, the multiply-accumulate (MAC) operation, which is a fundamental building block of CNNs, requires enormous arithmetic operations. As the input dataset size increases, the traditional processor-centric von-Neumann computing architecture becomes ill-suited for CNN-based applications. This results in exponentially higher latency and energy costs, making the processing of CNNs highly challenging.

To overcome these challenges, researchers have explored the Processing-In Memory (PIM) …

Modeling The Early Visual System, Nicholas Lanning

Theses and Dissertations--Electrical and Computer Engineering

There are two encoding schema present in simple cells in the early visual system of vertebrates: the retinal simple cells activate highly when the receptive field contains a center surround stimulus, while the primary visual cortex’s (V1) simple cells activate highly when the receptive field contains visual edges. Work has been done in the past to enforce constraints on visual machine learning such that the retinal or V1 encoding is learned, but this work is often done to emulate retinal and V1 encoding in a vacuum. Recent work using convolutional neural networks focuses on anatomical constraints along with a supervised …

N-Of-1 Trials: The Epitome Of Personalized Medicine?, Joyce P Samuel, Susan H Wootton, Jon E Tyson

Faculty, Staff and Student Publications

Observational studies are notoriously susceptible to bias, and parallel-group randomized trials are important to identify the best overall treatment for eligible patients. Yet, such trials can be expected to be a misleading indicator of the best treatment for some subgroups or individual patients. In selected circumstances, patients can be treated in n-of-1 trials to address the inherent heterogeneity of treatment response in clinical populations. Such trials help to accomplish the ultimate goal of all biomedical research, to optimize the care of individual patients.

Hist 190 Writing & History, Tracey L. Billado

Open Educational Resources

No abstract provided.

Unmet: The Undergraduate Experience Of Basic Need Insecurity At An Uncommon University, Michelle C. Bair, Rachelle V. Blackwell-Stegall, Sara E. Rafuse, Ra’Meer J. Roberts, Sara E. Weinstein

Doctor of Education Capstones

Virginia Commonwealth University’s (VCU) Dean of Students office submitted a Request for Assistance with needs related to food and housing insecurity and lack of basic funds for students. To address this request, a doctoral Capstone team conducted a problem and context analysis, literature review, student focus groups, and an internal survey of departments. The goal was to explore the undergraduate experience of unmet needs and to identify gaps and overlaps in basic needs support and services already provided at VCU. Findings suggest that students do not know the resources available to them through the Dean of Students office, that students …

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

Browse all Theses and Dissertations

Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …

Sleep And Health Behaviors In A Safety-Net Primary Care Setting, Sahar Sabet

Theses and Dissertations

Nearly half of all premature deaths in the United States are attributable to preventable and modifiable health risk behaviors. For decades, the leading behavioral health contributors to morbidity and mortality are tobacco use, physical inactivity, and alcohol consumption. Medication adherence is a relatively less studied yet critical interrelated health behavior that is tied to health and treatment outcomes. Sleep, an important pillar of health, is a daily and modifiable behavior that shows promise as a health behavior facilitator. Better understanding the dynamics of these modifiable health behaviors is essential for the improvement of health promotion, particularly among underserved populations (e.g., …

Exploring The Relationship Between The Epigenome And Metabolism In Mycn-Amplified Neuroblastoma, Krista M. Dalton

Theses and Dissertations

High risk neuroblastoma (NB) is responsible for nearly 15% of all cancer related deaths in the pediatric population. The transcription factor MYCN is the most studied oncogene in NB, automatically conferring high-risk and has been found to be difficult to target. One way that MYCN amplification in NB functions to support tumorigenicity is through altered metabolism, satisfying the demand for rapid proliferation by increasing the nutrient flux through biosynthetic pathways. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified NB is hypersensitive to the …

Advancing Social Equity And Promoting Black Self-Determination: A Community Garden Opportunity Plan For Richmond, Va, Alessandro U. Ragazzi

Master of Urban and Regional Planning Capstone Projects

Urban agriculture provides a variety of economic, environmental, and social benefits. Recognizing these benefits, the City of Richmond administers a community garden program known as “Richmond Grows Gardens.” Through this program, underutilized city properties are permitted for use as community gardens. However, an emerging concern is the potential for community gardens to perpetuate underlying structures of social and racial inequality through displacement and social exclusion. Considering these concerns, this plan investigates the implementation of community gardens in Richmond and establishes a methodology for ranking existing and available community garden sites based on the social and racial demographics of their surrounding …

Predicting Mountain Lion Resource Selection And Abundance In North America, William Connor O'Malley

Graduate Student Theses, Dissertations, & Professional Papers

The relationship between habitat quality and density is well documented in lower trophic levels but to what extent it can be extended to higher trophic levels is unknown. I tested the relationship between habitat quality, home-range size and density using a wide-ranging, well-studied, top carnivore, the mountain lion (Puma concolor). First, I created a second-order resource selection function (RSF) for mountain lions in their current North American range using GPS collar data from 476 individuals in 20 study sites and remotely-sensed landscape data. I used the RSF and home range estimates derived from collared animals to quantify mountain …

Semaglutide As A Possible Therapy In Binge Eating Disorder?, Rebecca Pearlman, Janaki Nimmagadda

UAB Huntsville Research Day - All Presentations

2023 clinical vignette poster

Adrenal Cancer Presenting As Bilateral Lower Extremity Edema And Hirsutism, Hunter Soleymani, Rafik Elbeblawy, Tyler Newell, Dyan Alvarez, Parekha Yedla

UAB Huntsville Research Day - All Presentations

2023 oral presentation

Situated Data: Feminist Epistemology And Data Curation, Scout Calvert

University of Nebraska-Lincoln Libraries: Faculty Publications

In the last decade or more, academic libraries have taken up the challenge of providing data curation and research data support, bringing expertise in metadata and digital preservation to key aspects of the research data life cycle. This activity has hastened since 2013, when the White House Office of Science and Technology Policy (OSTP) issued a memo directing federal funding agencies to require data, among other products of research, to be shared as a condition of funding.1 The OSTP memo did not come out of the blue, but recognized changes in data practice in some disciplines as the costs of …

Comparison Of Library Publishing Workflows By Open Access Model As Practiced In The University Of Nebraska–Lincoln Libraries, Sue Ann Gardner

University of Nebraska-Lincoln Libraries: Faculty Publications

Workflows for green and diamond open access (OA) models in a library publishing program may be very similar to one another (green = republishing; diamond = original publishing). As administered in the University of Nebraska–Lincoln Libraries, the details of each of these workflows are outlined and compared with each other and compared also with the interaction with authors that stems from gold OA (= outsourcing publishing). Vignettes related to each type of publishing model are included to demonstrate the types of conversations we tend to have with authors about the various OA types and give an indication of how much …

Applications Of Diversity Language To Descriptions Of Collection Development Activities At Academic Libraries: An Exploratory Analysis Of Strategic Plans And Diversity Information Webpages, David Macaulay

University of Nebraska-Lincoln Libraries: Faculty Publications

Diversity is commonly invoked as a goal for libraries in a variety of domains, including collections. This study explores how diversity language is used to characterize collection development efforts at a sample of large North American academic libraries, through content analysis of strategic planning documents as well as library webpages providing information about diversity efforts. The topic of collection diversity was found to be not consistently addressed in these documents. While 90% of the institutions whose strategic plans were examined mentioned diversity in some way, less than half of these did so in relation to collections; about one-third of the …