Using Gps-Defined Venue-Based Affiliation Networks Among Black Sexually Minoritized Men And Transgender Women To Identify Locations For Hiv Prevention Interventions, Yen-Tyng Chen, Cho-Hee Shrader, Dustin T Duncan, Abby E Rudolph, Seann D Regan, Byoungjun Kim, Jade Pagkas-Bather, Justin Knox, Kayo Fujimoto, John A Schneider

Faculty, Staff and Student Publications

Purpose: HIV biomedical intervention uptake is suboptimal among Black sexually minoritized men (SMM) and transgender women (TW). Venues where people meet and interact shape HIV-related risk and prevention behaviors. We aimed to construct GPS-defined venue-based affiliation networks and identify the unique set of venues that could maximize reach of HIV biomedical interventions among Black SMM and TW.

Methods: We used baseline survey and GPS data from 272 Black SMM and TW in the Neighborhoods and Networks (N2) Cohort Study in Chicago, Illinois (2018-2019). We mapped participants' GPS data to the nearest pre-identified SMM- and TW-friendly venue (n = 222) to …

Trends In Central Nervous System-Active Polypharmacy Among People With Multiple Sclerosis, Hayden Naizer, Joseph Wozny, Trudy Millard Krause, Ethan Huson, Leorah Freeman

Faculty, Staff and Student Publications

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

RESULTS: The …

"The Hotel Of 10,000 Stars": The Impact Of Social-Structural Determinants Of Health Among Im/Migrant Shrimpers In The Gulf Of Mexico, Shannon Guillot-Wright, Lacy Davis, Linh Truong, Heide Castañeda, Anabel Rodriguez

Faculty, Staff and Student Publications

Objectives. To identify appropriate interventions to prevent injury, we conducted a qualitative study among commercial shrimp fishermen in the Gulf of Mexico.

Methods. Using qualitative and participatory research methods, including interviews, photovoice, and workplace observations in southeast Texas and the Rio Grande Valley in Texas, we examined the social‒structural dimensions that contribute to physical and psychological injury.

Results. We found that multiple layers of vulnerability and danger exist among shrimpers with interacting themes: (1) recognizing risk, (2) precarious employment, and (3) psychological distress.

Conclusions. Our results add to the growing body of knowledge that emphasizes the negative health impacts of …

Does Every Move Really Count Towards Better Health?, Andrea Ramirez Varela, Pedro C Hallal

Faculty, Staff and Student Publications

No abstract provided.

Sexual Debut In Early Adolescence And Individual, School, And Neighborhood Social Capital, Camila Cribb Fabersunne, Carly Milliren, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, Paula M Cuccaro, Susan L Davies, Tracy Richmond

Faculty, Staff and Student Publications

Purpose: Sexual debut in early adolescence is associated with poor health outcomes in adulthood. We examined the associations of social capital within families, schools, and neighborhoods with early sexual debut.

Methods: Using data from the Healthy Passages cohort, a longitudinal multilevel study of adolescents, we performed a series of cross-classified multilevel logistic regression models to examine (1) the relative contribution of schools and neighborhoods to the variance and (2) the association of markers of social cohesion/social capital in families, schools, and neighborhoods with sexual debut by 10th grade.

Results: There were 4,001 youth participants nested in 115 schools and 751 …

Comprehensive Investigation Into The Molecular Mechanisms Driving The Emergence Of Emm4 Group A Streptococcus, Chioma Odo, Samuel A Shelburne, Anthony R. Flores, Steven J Norris, Anna Konovalova, Blake Hanson

Dissertations and Theses (Open Access)

Abstract

Comprehensive Investigation into the Molecular Mechanisms Driving the Emergence of emm4 Group A Streptococcus

Chioma Modeline Odo, M.S.

Advisory Professor: Samuel A. Shelburne, MD, Ph.D.

The major gram-positive bacterium group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it is well known to cause infections that occur in waves. GAS strains are grouped based on the composition of the N-terminal sequence of the M protein which is encoded by the emm gene. With the advent of large-scale whole genome sequencing, GAS clonal emergence events in emm1, emm3, and emm89 types have been identified …

Consistency Of Advanced Radiation Therapy Qa Methods And Global Auditing Systems, Fre'etta Brooks

Dissertations and Theses (Open Access)

Consistency of Advanced Radiation Therapy QA Methods and Global Auditing Systems

Fre’Etta M.D. Brooks, B.S.

Advisory Professor: Stephen F. Kry, Ph.D.

Abstract

Auditing systems provide a means to verify the implementation and operation of all equipment and radiation parameters used by an institution providing radiation therapy treatments. The systems are important tools that are used to determine if an institution can accurately deliver radiation therapy that requires complex planning in the form of IMRT or VMAT and credential radiotherapy treatment institutions for specific clinical trial protocols; to assure the quality of treatment to all patients. Auditing techniques vary by region …

Delineating Metastasis In Mss Colorectal Cancer By Single - Cell Rna Sequencing, Shuangjie You

Dissertations and Theses (Open Access)

Colorectal cancer Colorectal Cancer (CRC) is the leading cause of cancer-related deaths, with the majority of these deaths occurring after metastases. In this study, we used single-cell RNA transcriptome sequencing to characterize the cellular and molecular features of primary CRC and colorectal liver metastases (CRLM). Analysis of 130 samples revealed significant heterogeneity in the tumor microenvironment (TME) characterized by a diversity of cancer-associated fibroblasts, immune cells, and endothelial cell populations. Notably, we identified different CAF subtypes, including inflammatory (iCAFs), matrix(mCAFs), complement (cCAFs), and vascular (vCAFs). iCAFs were enriched in primary tumors expressing higher levels of inflammation-associated genes, whereas mCAFs were …

Single Cell And Spatial Analysis Characterize Metabolic Dpep1+ Fibroblasts In Pdac, Yuanyuan Zhu

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is highly malignant and exhibits aggressive progression patterns, resists conventional treatments, and poses significant challenges to patient survival, necessitating urgent research and development of novel therapeutic approaches. Understanding cancer-associated fibroblasts (CAF) metabolism reprogramming in PDAC tumor microenvironment (TME) may uncover novel therapeutic targets. Here, we used single cell and spatial transcriptomics to comprehensively characterize the TME content of human PDAC. We characterized CAFs metabotypes and a novel CAF population expressing DPEP1, COMP, CST1, which involved in glutathione metabolism, termed "gluCAFs” and was associated with poor clinical outcomes and advanced PDAC stages. We also validate the existence …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

Influential Factors And Predicting Dose Delivery Accuracy For Imaging And Radiation Oncology Core’S Phantom Program Using Machine Learning, Hunter Mehrens

Dissertations and Theses (Open Access)

IROC’s mission is to help ensure consistent and comparable, high-quality radiotherapy across clinics that participate in national clinical trials. To obtain this mission, IROC’s phantom program provides a third-party end-to-end check of the clinical workflow of a patient receiving radiotherapy. The goal of the phantom audit is to compare the dose delivered to the dose planned by the treatment system ensuring dose delivery accuracy. While IROC’s phantoms are better equipped to catch dose delivery errors compared to a clinic’s QA process, the end-to-end process and reporting of results is time-consuming creating a bottleneck for clinical trial participation. Furthermore, IROC’s passing …

The Role Of An Ultraconserved Long Non-Coding Rna In B-Cell Lymphomagenesis, Swati Mohapatra

Dissertations and Theses (Open Access)

Ultraconserved regions (UCRs) are genomic segments with perfect (100%) conservation between the orthologous regions of human, rat, and mouse genomes. UCRs can be transcribed into mono-exonic long non-coding RNAs (lncRNAs) known as transcribed ultraconserved regions (T-UCRs). These regions, despite lacking protein-coding potential, are increasingly recognized for their regulatory roles in gene expression, including the modulation of non-coding RNA (ncRNA) transcripts. NcRNAs play crucial roles in cellular processes, including oncogenic transformation, with emerging evidence revealing their ability to encode small peptides known as ncRNA-encoded peptides (ncPEPs). These peptides, originating from small open reading frames (smORFs), contribute to diverse cellular functions and …

The Role Of The Circadian Clock In Disease And Tissue Function, Marvin Wirianto

Dissertations and Theses (Open Access)

The mammalian circadian clock responds to the 24-hour daily cycle and regulates tissue-specific gene expression and downstream physiology. The central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN) synchronizes the peripheral clocks in different tissues. This dissertation aims to uncover specific circadian regulatory mechanisms in the brain and skeletal muscle.

Alzheimer’s Disease (AD) is the most common type of dementia. It has previously been shown that there is a strong correlation of disease progression with circadian rhythm decline. We showed that circadian modulation by a small molecule Nobiletin (NOB) was able to mitigate AD pathogenesis. Furthermore, NOB significantly alleviated the …

Genetic Analysis Of Kmt2d Loss In Tumorigenesis Using Genetically Engineered Mouse Models, Yingda Jiang

Dissertations and Theses (Open Access)

The Cancer Genome Atlas Program (TCGA) has discovered multiple tumor suppressors that are commonly mutated across a variety of human cancers, such as chromatin regulators in COMPASS and SWI/SNF complexes. KMT2D, a histone H3K4 methyltransferase in the COMPASS complex, is frequently mutated in human lymphoma, melanoma, and epithelial carcinoma. Biochemically, KMT2D shapes the cellular enhancer landscape as the major writer of the putative enhancer mark H3K4me1. Given the critical role of cellular enhancer landscape in determining cellular lineage in embryonic development, it is unknown whether enhancer dysregulation caused by KMT2D loss leads lineage switch of tumor cells, which has …

Vesicle-Associated Membrane Proteins In Airway Mucin Secretion, Boxuan Yang

Dissertations and Theses (Open Access)

Mucus plays a vital role in shielding the lungs against harmful substances such as particles, pathogens, and chemicals inhaled from the environment. It captures these harmful elements, and ciliary action helps to expel them from the lungs. Paradoxically, malfunctioning of mucus induces the development of various respiratory illnesses, including asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. Despite extensive research on controlling mucin production and hydration, the process of secretion is not yet fully comprehended.

Mucin undergoes regulated secretion at two rates: a low baseline rate and a high stimulated rate. Over the past 25 years, …

Evaluation Of Myogenic Differentiation Potential Of Bmd Ipscs In Vitro And The Effect Of Ubiquitination Inhibitors On Dystrophin Stability In Vivo, Muchen Liu

Dissertations and Theses (Open Access)

Background: Muscular dystrophies are heterogeneous groups of inherited diseases leading to progressive muscular weakness and degeneration. In the case of Becker muscular dystrophy (BMD), non-disrupting mutations of the DMD gene reading frame is the causative defect. By the age of 30s, about 60 to 70% of BMD patients develop cardiomyopathy, which is often lethal. Unfortunately, there is currently no cure for BMD. Meanwhile, improvement of dystrophin stability by repressing polyubiquitination is a promising strategy. The application of human iPSCs in tissue regeneration also serves as a potential therapeutic strategy. This study aims to test the efficacy of selected drugs interfering …

Recommendations And Implementation Considerations For The Routine Collection Of Sexual Orientation And Gender Identity Data In Research And Practice, Irene Tamí-Maury, Thomas J Millett

Faculty, Staff and Student Publications

No abstract provided.

Plasma Proteins Associated With Plant-Based Diets: Results From The Atherosclerosis Risk In Communities (Aric) Study And Framingham Heart Study (Fhs), Hyunju Kim, Jingsha Chen, Brenton Prescott, Maura E Walker, Morgan E Grams, Bing Yu, Ramachandran S Vasan, James S Floyd, Nona Sotoodehnia, Nicholas L Smith, Dan E Arking, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background & aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

Methods: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics …

Past-Year Hiv Testing, Current Antiretroviral Therapy Use, And Participation In Services For People Who Inject Drugs, Itunu Sokale, Johnny Wilkerson, Paige Wermuth, Folefac Atem, Janet Burnett, Cyprian Wejnert, Salma Khuwaja, Catherine Troisi

Faculty, Staff and Student Publications

Evaluating routine HIV testing and treatment and use of services for people who inject drugs (PWID) is critical to curb the ongoing HIV epidemic. We analyzed data from the 2018 National HIV Behavioral Surveillance of PWID aged 18 years or older, recruited using respondent-driven sampling and offered anonymous HIV testing after survey. We performed bivariate and multivariable analyses with log-linked Poisson regression of the generalized linear models to examine the associations between demographics and PWID service use, past-year HIV testing, and current antiretroviral therapy (ART) use. Among 10,311 HIV-negative PWID, 56% reported past-year HIV testing, and of the 553 HIV-positive …

Analyzing Heterogeneity In Biomarker Discriminative Performance Through Partial Time-Dependent Receiver Operating Characteristic Curve Modeling, Xinyang Jiang, Wen Li, Kang Wang, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. …

E-Cigarette Use Reasons And Associated E-Cigarette Use Dependence Among College Students: A Longitudinal Examination, Tzung-Shiang Ou, Anne Buu, James J Yang, Hsien-Chang Lin

Faculty, Staff and Student Publications

Objective: Previous studies have established an understanding of reasons for e-cigarette use and associated e-cigarette use patterns such as use frequency, yet the critical extension to associated e-cigarette dependence outcome remains under-researched. This study used longitudinal data to examine whether the reasons for e-cigarette use predict a higher/lower level of e-cigarette dependence.

Methods: This study recruited college students who were current e-cigarette users from Fall 2019 to Fall 2020 (four semesters) at three public universities in the Midwest and South of the U.S. Those who participated for at least two semesters were included (N = 366). Data were collected using …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

The Effect Of Context Diversity In Virtual Reality Environments On Speech Motor Learning In A Person With Aphasia And Apraxia Of Speech, Shelby Keeler Holloway

Theses and Dissertations

This study explored the effect of contextual diversity on speech motor learning in an individual with apraxia of speech (AOS) using virtual reality (VR). One 62-year-old participant with severe AOS participated in the study where he practiced monosyllabic CVC words in both consistent and diverse VR environments. Kinematic, acoustic, and perceptual data were collected and evaluated for evidence of learning. Kinematic data were collected using electromagnetic articulography where sensors were glued to the participant's upper lip, lower lip, tongue blade, and tongue tip and were tracked with high precision. In addition, acoustic and perceptual data were collected using a microphone …

Chancery Court Demonstrates Willingness To Apply Context-Specific Tests In Assessing Challenges To Advance Notice Bylaws, Robert S. Reder, Noah Nance

Vanderbilt Law School Faculty Publications

It is well established," under Delaware law, "that stockholders have a fundamental right to 'vote for the directors that the s[tock]holder[s] want [] to oversee the firm.'" Sternlicht v. Hernandez, 2023 WL 3991642 (Del. Ch. June 14, 2023) ("Sternlicht"). Moreover, "[s]ubsumed within that fundamental right to vote is the right to nom- inate a competing slate." Despite this recognition, the Delaware Gen- eral Corporation Law "is silent as to how a stockholder may propose a nominee for election." Strategic Inv. Opportunities LLC v. Lee Enters., Inc., 2022 WL 453607 (Del. Ch. Feb. 14, 2022) ("Strategic Investment Opportunities"). "[T]o fill this …

The Effect Of Employee-Oriented Hrm On Employee Downsizing Following Mergers & Acquisitions, Pingshu Li, Mengwei Li, Hyesook Chung, Clint Chadwick

Management Faculty Publications

Firms have increasingly engaged in Mergers and Acquisitions (M&A) activities in recent years. A common strategy following M&A is employee downsizing that aims at achieving strategic goals and enhancing performance. This approach, however, raises concerns from a strategic human resource management (HRM) perspective. Research suggests that downsizing may breach employees' psychological contracts and hinder the development of firm-specific human capital. While this viewpoint has an intuitive appeal, we reconsider it by suggesting that, in the M&A context wherein employees expect significant organizational changes, downsizing does not necessarily lead employees to negative reactions. Instead, if acquiring firms have strong employee-oriented HRM …

Essays On Cho: An Investigation Of Industrially Relevant Stressors In Recombinant Protein Production, Benjamin Synoground

All Dissertations

Recombinant protein therapeutics have become integral in the treatment and prevention of an increasingly broad range of diseases and conditions. The vast majority of these biopharmaceuticals are produced in Chinese hamster ovary (CHO) cells due to their well-established expression systems, scalability, and ability to produce safe, human-compatible glycoproteins. Previous research has aimed to increase productivity while maintaining or improving product quality metrics, resulting in substantial improvements in product yields over the past forty years. This progress has been largely driven by 'omics and multivariate approaches, which offer valuable mechanistic insights and identify process bottlenecks.

Within this dissertation, CHO cell stress …

Investigating The Etiology, Epidemiology, And Ecology Of Blackberry Yellow Vein Disease In South Carolina, Wanita Dantes

All Dissertations

Blackberry production is growing in popularity in the southeastern U.S. However, blackberry growers in this region report major problems with productivity and longevity due to viruses. First, the state of knowledge on blackberry yellow vein disease (BVYD) complex, associated with mixed infections of a diverse group of viruses, is discussed. Specific viruses associated with symptom types are unknown. Therefore, the etiology of BYVD is not fully understood, which makes BYVD diagnosis challenging. My research focused on improving BYVD diagnosis, etiology, and epidemiology. Second, I developed a farm-level diagnostic protocol to improve virus disease surveillance. High throughput sequencing detected 17 known …

Don't Waste Our Time: Key Transformative Structures For Fast Track Learning, Carlita S. King

All Dissertations

Following a massive wave of school closures during the COVID-19 pandemic, educators found the need to be hyper-critical of how they spend their instructional time with students. Almost all students are expected to return nearly a full grade-level behind and would likely have to learn to navigate a completely new school environment. As a result, many educators were overwhelmed to cover unprecedented amounts of instructional content in less time. High-intensity tutoring programs have been known to have the potential to help struggling students advance their skills and gain up to three additional months of learning within a few sessions. The …

Effect Of Long-Term Use Of Antimicrobials On Commonly Used Surfaces In Foodservice Establishments, Anuradhi Bandaranayake

All Dissertations

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