Medicine and Health Sciences Commons^™

Factors Associated With Early Onset Anal Cancer And Facilitators And Barriers To Screening Among Men Living With Hiv And Their Providers In The Deep South: A Mixed Methods Investigation, Anna Junkins

All ETDs from UAB

For my dissertation work, I aimed to 1) determine the occurrence of early onset (diagnosis at <50 years) anal cancer and the impact of HIV infection and other risk factors, and 2) utilize a mixed methods research approach to identify and explain factors associated with screening among men living with HIV (MLHIV) and their providers. In Aim 1, I used logistic regression to estimate the odds of early onset cancer by sociodemographic and clinical characteristics among anal cancer patients in the Alabama cancer registry from 2012-2018. Among 519 patients, 17.7% were diagnosed at <50 years. Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients and disproportionately lived in areas with higher social vulnerability. In Aim 2, I used logistic regression to estimate the odds of anal cancer screening by sociodemographic and sexual risk characteristics among MLHIV using retrospective survey data from 1917 Clinic in 2018. Among 1,114 men, 52% had received an anal pap within one year of completing the survey. Men who were screened were more likely to have multiple sexual partners. Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Older Black men were less likely to be screened. In Aim 3, I used thematic analyses to identify themes related to health beliefs, barriers and facilitators, and perceived and evaluated need of screening using in-depth interviews among MLHIV and their providers. Benefits of screening among MLHIV were early detection and awareness about one’s body. Suggestions for overcoming barriers to screening among providers included screening guidelines, patient education, inclusion of screening into routine care, and self-collection. Among men that were aware of HPV-associated cancers, there was perceived risk and desire to receive HPV vaccination. Individuals who are male, Black, or living with HIV may be at increased risk of developing anal cancer younger. Among MLHIV, improving education about HPV-associated cancer, and offering self-collected screening as part of routine care could facilitate screening in the South.

Cross-Sectional Retrospective Study To Determine The Prevalence Of Periodontal Bone Loss As A Function Of Age In The Predoctoral Clinic Patient Population, Lincoln Nguyen

All ETDs from UAB

Age has a significant effect on the body’s ability fight off disease, recover, and maintain collagen structures, and it has been observed that older adults have a higher prevalence of periodontal diseases. Studies have shown that age is a risk factor for alveolar bone loss. However, there is a lack of research done looking at if this is a linear progression or if there is a specific age that susceptibility increases. The aim of this study is to investigate (1) changes in radiographic bone loss in varying age groups in the University of Alabama patient population and (2) to evaluate …

Improving Direct Oncolytic Effect Of Oncolytic Hsv To Overcome Therapeutic Resistance Of Brain Tumors, Sam Edward Gary

All ETDs from UAB

Central nervous system tumors, especially malignant brain tumors, account for the most years of potential life lost in adults and children with cancer. Malignant brain tumors are typically fatal cancers due to their highly aggressive nature, inability to obtain gross total resection, location in sensitive brain areas, and intra- and intertumoral heterogeneity, making therapeutic targeting difficult. High-grade glioma (HGG), malignant brain tumors of glial cell origin invariably recur due to intrinsic and adaptive resistance mechanisms against standard therapies. Therefore, novel treatments that overcome therapeutic resistance are desperately needed. One promising approach is oncolytic viruses (OVs), which achieve tumor regression by …

Investigating Molecular Mechanisms Behind Neuronotypic Gba1 Mutations In Lewy Body Dementias, Casey Mahoney-Crane

All ETDs from UAB

Nonmotor deficits are present in nearly all Parkinson’s disease (PD) patients, with ~80% of these patients developing dementia. Importantly, expression of the severe GBA1 L444P heterozygous mutation increases the risk for Parkinson’s disease devel-opment by 5.43 times compared to mild mutation carriers. Currently, many PD treat-ments predominately focus motor symptoms, while treatments for nonmotor symptoms, such as visual-spatial difficulties and dementia, focus on symptom management and continue to remain elusive. Therefore, understanding the molecular mechanisms behind these nonmotor symptoms is essential for the development of effective therapeutics leading to slower disease progression. The work presented in this dissertation sought to …

O-Glcnacylation And Modulation Of Gabaergic Transmission, Shekinah Phillips

All ETDs from UAB

Changes in the strength of GABAergic transmission is heavily influenced by posttranslational modifications and allosteric modulators like benzodiazepines and neurosteroids. O-GlcNAcylation (O-GlcNAc) is a post-translational modification that is tightly regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add or remove the O-GlcNAc moiety of β–N-acetylglucosamine to serine and threonine residues on proteins, respectively. Published reports from our lab have demonstrated that an acute increase in O-GlcNAcylation induces a long-term depression (LTD) of evoked GABAAR mediated IPSCs (eIPSCs) and reduces the amplitude and frequency of spontaneous IPSC (sIPSC) in hippocampal principal cells, however the mechanism in which this occurs is …

Elementary Cone Photoreceptor Signals In V1 Neurons, Cyril Nyankerh

All ETDs from UAB

Daylight vision is initiated by the activation of cone photoreceptors in the retina in response to light, thereby generating spatial and temporal patterns of photoreceptor signals. Subsequent to this, the signals are combined and processed in downstream neural circuits, ultimately contributing to the formation of receptive fields of neurons in primary visual cortex (V1). Recent advances in adaptive optics (AO) have enabled imaging of the retina with near diffraction limited resolution, allowing for the probing of the visual system's processing at the resolution of individual cones. The central theme of this dissertation characterizes quantitively and qualitatively the physiological responses of …

Blood Transfusion Factors That Affect The Outcomes Of Patients Who Experienced Trauma-Related Hemorrhage, Justin Lee Miller

All ETDs from UAB

Trauma is a leading cause of death in the United States and in the world. It is the leading cause of death of Americans between the ages of one to 45 years old and is expected to increase due to increase over the next ten years. Most trauma deaths are attributed to hemorrhage and are considered preventable. The current standard of care for trauma-related hemorrhage (TRH) is damage control resuscitation using either whole blood (WB) or blood components (BC) in a ratio of 1 unit of red blood cells to 1 unit of plasma to 1 unit of platelets. The …

The T Cell Response In A Mouse Model Of Multiple System Atrophy, Nicole Jane Corbin-Stein

All ETDs from UAB

Multiple System Atrophy (MSA) is a fatal and rare demyelinating synucleinopathy, characterized by the accumulation of alpha-synuclein (α-syn) in glial cytoplasmic inclusions (GCIs) within oligodendrocytes. This condition is marked by neuroinflammation, demyelination, and neurodegeneration in areas showing GCI pathology, involving antigen presentation by myeloid cells and infiltration of CD4+ and CD8+ T cells. Despite strong evidence of neuroinflammation in post-mortem MSA tissue, the specific mechanisms driving the disease pathogenesis remain elusive. In prior research using the Olig001-SYN mouse model, which involves the modified AAV vector, it was shown that depleting CD4+ T cells can reduce neuroinflammation and demyelination. Notably, this …

Investigation On The Epigenetic Mechanisms Modified By Dietary Phytochemicals In Inhibiting Mammary Cancer, Mohammad Mijanur Rahman

All ETDs from UAB

Breast cancer (BC) is global burden for the health of women. It is the most commonly diagnosed cancer in women and the second leading cause of cancer mortality among women in the United States. One in every eight women in the USA has a chance of developing invasive BC in her lifetime. The limitations of the available therapeutics for BC treatment have brought the dietary prevention of BC to the attention of the scientific community as a safe, natural, and easy to implement therapeutic strategy. In this regard, our laboratory with many other laboratories have demonstrated the anti-BC effect of …

The Effect Of Lower Limb Neuromuscular Electrical Stimulation On The Muscle And Metabolic Health After Acute Spinal Cord Injury, Amal Alharbi

All ETDs from UAB

Spinal cord injury (SCI) is a devastating event with long-term consequences for individuals and their families. It causes immediate disruption to neuronal pathways, leading to paralysis and loss of muscle function below the injury level. A few weeks after the injury, there is a rapid decline in contractile activity, muscle mass, and cross-sectional area. This leads to muscle fiber degeneration and a shift towards a higher proportion of fast glycolytic fibers, which are more prone to fatigue and less efficient in energy utilization. Severe muscle atrophy in SCI is closely linked to metabolic dysfunction, affecting overall health and rehabilitation recovery. …

Hydrogen Peroxide Regulates Protein N-Glycosylation, Alexandria Hernandez-Nichols

All ETDs from UAB

N-glycosylation is a co- and post-translational modification wherein a variety of sugars are added to proteins in a linear pathway progressing from high mannose (HM) to hybrid, to complex type N-glycans. This modification is important to the understanding of protein maturation, stability, and function. Studies have shown that changes in cell N-glycomes, in particular, the HM N-glycan category, could be hallmarks of various pathologies. The biosynthetic pathway for N-glycosylation is well studied and the key enzymes involved in the progression of HM to hybrid N-glycans are the a-mannosidases. Little is understood about the regulation of this highly complex post-translational modification …

The Association Between Social Connectedness And Opioid Reuse Among Vulnerable Groups Receiving Medication For Opioid Use Disorder, Jolanda Lynn Hudson

All ETDs from UAB

THE ASSOCIATION BETWEEN SOCIAL CONNECTEDNESS AND OPIOID REUSE AMONG VULNERABLE GROUPS RECEIVING MEDICATION FOR OPIOID USE DISORDER JOLANDA L. HUDSON PUBLIC HEALTH ABSTRACT Introduction: Opioid Use Disorder (OUD) is a serious illness that continues to persist despite the many efforts of researchers, physicians, government agencies, state, and local programs, to eliminate the mortality rate associated with this disease. Although manageable, OUD is still taking the lives of citizens due to illegal opioid misuse. Understanding the dynamics of the disease and the contributing factors in various populations may inform researchers in successful intervention outcomes. Methods: A retrospective secondary data analysis utilizing …

Changes In Drug And Alcohol Behaviors Before And After An Educational Intervention Among At-Risk Adults And Youth, Isabel Cuellar Acker

All ETDs from UAB

Introduction: Substance abuse is defined as the excessive use of a drug in a way that is detrimental to oneself, society, or both. Gender is important to examine because it is becoming more common for females to develop substance use disorders and for their substance use to be more severe. This study will address the role of an education-based intervention on substance abuse in an area that is at the intersection of rural and urban geography with a unique pool of participants. Methods: This is a longitudinal cohort study that has a pre-post intervention design. A linear model was used …

Prevention Of Spina Bifida Through Fortification Of Iodized Salt With Folic Acid, Anastasia Arynchyna Smith

All ETDs from UAB

The overarching goal of the three-paper dissertation is to address the gaps in the literature on the clinical care burden of preventable spina bifida on the global neurosurgical community and the need for a universal food vehicle for fortification with folic acid as a novel prevention strategy. It is known that sufficient intake of folic acid is imperative to prevent neural tube defects (spina bifida) in the developing fetus in the first month post-conception. It is also known that fortifying staple foods is the most cost-saving and effective prevention method. However, very few countries have mandatory fortification policies. Therefore, the …

It's A Man's World: The Association Between Safe Sex Practices, Relationship Power, & Resilience Among African American Emerging Adults Between 18-24 In The Deep South, Jessica Morgan

All ETDs from UAB

The purpose of this dissertation was to examine the impact that power imbalance has on safe sex practices among African American emerging adults. The objectives included: provide a thorough review of preexisting literature that explores the impact of power imbalance on safe sex practices among African American women; understand the impact that power imbalance has on safe sex practices among African American emerging adults comparing data from men and women; and understand if resilience is associated with power imbalance among African American emerging adult women in the United States. Utilizing a retrospective, cross-sectional, quantitative study design, three methods were used …

Long-Term Longitudinal Analysis Of 4,187 Participants Reveals Insights Into Determinants Of Clonal Hematopoiesis, Md Mesbah Uddin, Seyedmohammad Saadatagah, Abhishek Niroula, Bing Yu, Whitney E Hornsby, Shriienidhie Ganesh, Kim Lannery, Art Schuermans, Michael C Honigberg, Alexander G Bick, Peter Libby, Benjamin L Ebert, Christie M Ballantyne, Pradeep Natarajan

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CHIP. Splicing factor genes (SF3B1, SRSF2, U2AF1, and ZRSR2) and TET2 CHIP grow significantly faster than DNMT3A non-R882 clones. We find that age at baseline and sex significantly …

Genome-Wide Association Study Meta-Analysis Of Neurofilament Light (Nfl) Levels In Blood Reveals Novel Loci Related To Neurodegeneration, Shahzad Ahmad, Mohammad Aslam Imtiaz, Aniket Mishra, Ruiqi Wang, Marisol Herrera-Rivero, Joshua C Bis, Myriam Fornage, Gennady Roshchupkin, Edith Hofer, Mark Logue, W T Longstreth, Rui Xia, Vincent Bouteloup, Thomas Mosley, Lenore J Launer, Michael Khalil, Jens Kuhle, Robert A Rissman, Genevieve Chene, Carole Dufouil, Luc Djoussé, Michael J Lyons, Kenneth J Mukamal, William S Kremen, Carol E Franz, Reinhold Schmidt, Stephanie Debette, Monique M B Breteler, Klaus Berger, Qiong Yang, Sudha Seshadri, N Ahmad Aziz, Mohsen Ghanbari, M Arfan Ikram

Faculty, Staff and Student Publications

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify …

Nurse Educators’ Experiences In Implementing Concept-Based Teaching, Ma Camlaria Felismino

Walden Dissertations and Doctoral Studies

The National League for Nursing called for implementing innovative teaching strategies in nursing education. Concept-based teaching (CBT) is a method that encourages learners to interpret, analyze, and integrate knowledge. Despite reports that CBT improves student outcomes and enhances critical thinking, the adoption of CBT is slow. This qualitative descriptive study, guided by Rogers’s diffusion of innovations theory, explored how nurse educators have experienced implementing CBT. Secondary data were analyzed from interviews conducted with 13 participants. Using constant comparative analysis, seven key themes emerged and were linked to the successful adoption and implementation of CBT: communication, learning from established programs, curriculum …

Bridging Implementation Science And Human-Centered Design: Developing Tailored Interventions For Healthier Eating In Restaurants, Melissa Fuster, Shelby Hipol, Terry Tk Huang, Uriyoán Colón-Ramos, Cara Conaboy, Rosa Abreu, Lourdes Castro Mortillaro, Margaret A. Handley

Publications and Research

Restaurants are important institutions in the communities’ economy with the potential to promote healthier foods but have been under-engaged in public health nutrition efforts. In particular, independently owned, minority-serving and minority-owned restaurants, remain under-represented in nutrition promotion efforts despite disproportionate burdens of diet-related health outcomes among minority populations. Addressing this gap in engagement, we undertook a process of co-designing and implementing healthy eating-focused interventions in two Latin American restaurants in New York City, combining the Behavior Change Wheel intervention development framework with a Human-Centered Design approach. Restaurant owners and chefs were involved in the research synthesis and solution development processes, …

A Five-Year Review Of State Dental Board Disciplinary Actions, Phorum Desai

All ETDs from UAB

Introduction: Ethical violations not only tarnish the reputation of dental professionals but also compromise the trust patients place in the dental field. A review of documented legal violations provides valuable insights into the common ethical transgressions and potential deficiencies in dental ethics education. This study aims to identify common violations reported by state dental boards and trends of violations over five years. Material and Methods: After a broad preliminary search, nine state dental boards with fully accessible records from January 2017 to December 2021 were selected for a thorough review: California, Iowa, Kentucky, Maine, Minnesota, Nebraska, New Jersey, South Dakota, …

Impact Of Alpha-Synuclein Aggregates On Synaptic Structure In The Amygdala, Nolwazi Zakithi Gcwensa

All ETDs from UAB

Parkinson’s disease is the most common motor neurodegenerative and is characterized by intracellular inclusions of misfolded protein α-synuclein termed Lewy Pathology. At least 80% of PD sufferers also experience non-motor symptoms along with, and sometimes preceding, the motor symptoms. Symptoms such as apathy, hallucinations, anxiety and depression could be caused by α-synuclein inclusions causing dysfunction in the amygdala. Lewy pathology in the amygdala of PD patients is robust and has also been observed in a number of other diseases like Dementia with Lewy Bodies and Alzheimer's disease. In our lab, we have shown that using preformed fibrils to induce α-synuclein …

Interactions Between Oral Cancer Cells And Enterococcus Fecalis And Their Impact On Perineural Invasion, Sree Ramya Bhamidipaati

All ETDs from UAB

Oral and oropharyngeal squamous cell cancers (OSCC and OPSCC) are some of the most common cancers in the world. The overall 5-year survival rate is 68.5%, which drops to 39.3% in patients with later-stage cancers. This research aims to evaluate the effects of Enterococcus faecalis (E. faecalis) on the OSCC and OPSCC's tumor progression. E. faecalis is associated with asymptomatic, persistent endodontic infections and was found at a higher rate in OSCC patients. We hypothesize that cancer cells and Enterococcus faecalis (Ef) interact to affect the tumorigenic properties of oral cancer cells. OSCC cells from different parts of the oral …

Understanding Biopsychosocial Influences On Physical Activity And Quality Of Life In Breast Cancer Survivors, Erica A. Schleicher

All ETDs from UAB

Receiving a breast cancer diagnosis and subsequent treatment can be life-altering, presenting numerous challenges. Breast cancer treatments are effective at allowing women to live longer, but often impose long-term side-effects that survivors must manage for years. Exercise is an effective way to address many long-term side-effects of breast cancer treatment, yet 63-83% of breast cancer survivors do not meet recommended physical activity (PA) guidelines. Due to the complexity of cancer and treatment options, cancer-related factors have potential biopsychosocial impacts that can influence exercise habits, attitudes toward PA (i.e., social cognitive theory (SCT) constructs), and potentially quality of life (QoL). It …

The Effect Of Progranulin On Lysosomal Function In Bv2 Cells, Michelle Park

All ETDs from UAB

Neurodegenerative diseases afflict nearly 7 million people in United states, constituting a significant portion of the 600 known neurological disorders. Characterized by the gradual loss of neurons and axons within the central nervous system (CNS), these conditions stem from chronic inflammatory activation of the brain. Chronic inflammation disrupts important processes such as autophagy lysosome pathway, a self-degradative process that eliminates protein aggregates and damaged organelles. Trehalose, a non-reducing disaccharide that triggers autophagic flux in neuronal cells and promotes the clearance of protein aggregates; however, without understanding the mechanism behind how trehalose affects these functions, it lacks value. In our study, …

Parp-1 Selectively Impairs Kras-Driven Phenotypic And Molecular Features In Intrahepatic Cholangiocarcinoma, Friederike L Keggenhoff, Darko Castven, Diana Becker, Stojan Stojkovic, Jovana Castven, Carolin Zimpel, Beate K Straub, Tiemo Gerber, Harald Langer, Patricia Hähnel, Thomas Kindler, Jörg Fahrer, Colm J O'Rourke, Ursula Ehmer, Anna Saborowski, Lichun Ma, Xin Wei Wang, Timo Gaiser, Matthias S Matter, Christian Sina, Stefanie Derer, Ju-Seog Lee, Stephanie Roessler, Bernd Kaina, Jesper B Andersen, Peter R Galle, Jens U Marquardt

Faculty, Staff and Student Publications

Objective: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.

Design: PARP-1 inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in KRAS-mutant, non-mutant cells. In addition, Parp-1 knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular …

The Kras Mutational Spectrum And Its Clinical Implications In Pancreatic Cancer, Luigi Perelli, Giannicola Genovese, Giulio F Draetta

Faculty, Staff and Student Publications

In this issue of Cancer Cell, McIntyre et al. show that specific mutations in the KRAS proto-oncogene shape clinical progression of pancreatic ductal adenocarcinoma (PDAC). Importantly, they find that the KRASG12R mutation is enriched in early-stage PDAC, and it is characterized by distinctly activated molecular programs.

The Kras Mutational Spectrum And Its Clinical Implications In Pancreatic Cancer, Luigi Perelli, Giannicola Genovese, Giulio F Draetta

Faculty, Staff and Student Publications

In this issue of Cancer Cell, McIntyre et al. show that specific mutations in the KRAS proto-oncogene shape clinical progression of pancreatic ductal adenocarcinoma (PDAC). Importantly, they find that the KRASG12R mutation is enriched in early-stage PDAC, and it is characterized by distinctly activated molecular programs.

Fibrotic Response To Anti-Csf-1r Therapy Potentiates Glioblastoma Recurrence, Spencer S Watson, Anoek Zomer, Nadine Fournier, Joao Lourenco, Manfredo Quadroni, Agnieszka Chryplewicz, Sina Nassiri, Pauline Aubel, Simona Avanthay, Davide Croci, Erik Abels, Marike L D Broekman, Douglas Hanahan, Jason T Huse, Roy T Daniel, Monika E Hegi, Krisztian Homicsko, Giulia Cossu, Andreas F Hottinger, Johanna A Joyce

Faculty, Staff and Student Publications

Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment …

Training Robust T1-Weighted Magnetic Resonance Imaging Liver Segmentation Models Using Ensembles Of Datasets With Different Contrast Protocols And Liver Disease Etiologies, Nihil Patel, Adrian Celaya, Mohamed Eltaher, Rachel Glenn, Kari Brewer Savannah, Kristy K Brock, Jessica I Sanchez, Tiffany L Calderone, Darrel Cleere, Ahmed Elsaiey, Matthew Cagley, Nakul Gupta, David Victor, Laura Beretta, Eugene J Koay, Tucker J Netherton, David T Fuentes

Faculty, Staff and Student Publications

Image segmentation of the liver is an important step in treatment planning for liver cancer. However, manual segmentation at a large scale is not practical, leading to increasing reliance on deep learning models to automatically segment the liver. This manuscript develops a generalizable deep learning model to segment the liver on T1-weighted MR images. In particular, three distinct deep learning architectures (nnUNet, PocketNet, Swin UNETR) were considered using data gathered from six geographically different institutions. A total of 819 T1-weighted MR images were gathered from both public and internal sources. Our experiments compared each architecture's testing performance when trained both …

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• Regeneron's Immersive Drug Development Elective Equips Future Physicians with Unique Industry Insights
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