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Full-Text Articles in Medicine and Health Sciences

The Significant Associations Between Epigenetic Clocks And Bladder Cancer Risks, Yang Deng, Chia-Wen Tsai, Wen-Shin Chang, Yifan Xu, Maosheng Huang, Da-Tian Bau, Jian Gu Jun 2024

The Significant Associations Between Epigenetic Clocks And Bladder Cancer Risks, Yang Deng, Chia-Wen Tsai, Wen-Shin Chang, Yifan Xu, Maosheng Huang, Da-Tian Bau, Jian Gu

Faculty, Staff and Student Publications

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for …


The Influence Of Childhood Trauma On Dna Methylation Patterns And Sex-Specific Cortisol Stress Reactivity: A Secondary Analysis, Isabella F. Correia Jun 2024

The Influence Of Childhood Trauma On Dna Methylation Patterns And Sex-Specific Cortisol Stress Reactivity: A Secondary Analysis, Isabella F. Correia

USF Tampa Graduate Theses and Dissertations

Childhood trauma has been shown to significantly impact physical and mental health outcomes, leading to conditions such as heart disease, diabetes, depression, and difficulties in decision-making and maintaining relationships. Exposure to such trauma has the potential to dysregulate an individual’s stress response system, resulting in abnormal cortisol levels. Many studies suggest a lasting impact of early-life stress on DNA methylation patterns and, separately, cortisol stress reactivity. In addition, there are known sex differences in exposure to childhood trauma and cortisol reactivity; yet studies to date have not investigated whether there is an association to DNA methylation. This study utilized a …


Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee Jun 2024

Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee

USF Tampa Graduate Theses and Dissertations

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2T61I mutation being the most widely studied. We generated the first transgenic mouse models expressing human CHCHD2WT and the PD-linked CHCHD2T61I mutation driven by the mPrP promoter. CHCHD2T61I Tg, but not CHCHD2WT Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, …


Developing A Fit-For-Purpose Composite Symptom Score As A Symptom Burden Endpoint For Clinical Trials In Patients With Malignant Pleural Mesothelioma, Charles S Cleeland, Karen N Keating, Brian Cuffel, Cem Elbi, Jonathan M Siegel, Christoph Gerlinger, Tara Symonds, Jeff A Sloan, Amylou C Dueck, Andrew Bottomley, Xin Shelley Wang, Loretta A Williams, Tito R Mendoza Jun 2024

Developing A Fit-For-Purpose Composite Symptom Score As A Symptom Burden Endpoint For Clinical Trials In Patients With Malignant Pleural Mesothelioma, Charles S Cleeland, Karen N Keating, Brian Cuffel, Cem Elbi, Jonathan M Siegel, Christoph Gerlinger, Tara Symonds, Jeff A Sloan, Amylou C Dueck, Andrew Bottomley, Xin Shelley Wang, Loretta A Williams, Tito R Mendoza

Faculty, Staff and Student Publications

We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma …


Stakeholder Involvement And Systematic Review Of Elements That Determine A Successful Return To Work For Injured Workers: A Scoping Review, Sundip Kaur Khosa, Wilma Jelley Professor Jun 2024

Stakeholder Involvement And Systematic Review Of Elements That Determine A Successful Return To Work For Injured Workers: A Scoping Review, Sundip Kaur Khosa, Wilma Jelley Professor

Internet Journal of Allied Health Sciences and Practice

Introduction: A healthy and sustainable return to work (RTW) for a worker after injury or illness has benefits for the worker, their family, the employer, and society.1 For this research we used the following definition of RTW success; return to positive and meaningful work in a position or occupation not necessarily including all the aspects of the worker’s pre-injury or pre-illness functions or tasks. Purpose: The question behind this survey-based research was, What elements are perceived as essential, to ensure return to employment of injured or ill workers, by stakeholders with experience in the RTW process? Methods: A 32 …


Mettl3-Mediated Chromatin Contacts Promote Stress Granule Phase Separation Through Metabolic Reprogramming During Senescence, Chen Wang, Hideki Tanizawa, Connor Hill, Aaron Havas, Qiang Zhang, Liping Liao, Xue Hao, Xue Lei, Lu Wang, Hao Nie, Yuan Qi, Bin Tian, Alessandro Gardini, Andrew V Kossenkov, Aaron Goldman, Shelley L Berger, Ken-Ichi Noma, Peter D Adams, Rugang Zhang Jun 2024

Mettl3-Mediated Chromatin Contacts Promote Stress Granule Phase Separation Through Metabolic Reprogramming During Senescence, Chen Wang, Hideki Tanizawa, Connor Hill, Aaron Havas, Qiang Zhang, Liping Liao, Xue Hao, Xue Lei, Lu Wang, Hao Nie, Yuan Qi, Bin Tian, Alessandro Gardini, Andrew V Kossenkov, Aaron Goldman, Shelley L Berger, Ken-Ichi Noma, Peter D Adams, Rugang Zhang

Faculty, Staff and Student Publications

METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase …


Contribution Of Matrix Metalloproteinase-2 And Matrix Metalloproteinase-9 To Upper Tract Urothelial Cancer Risk In Taiwan, Bo-Ren Wang, Hung-Huan Ma, Chao-Hsiang Chang, Cheng-Hsi Liao, Wen-Shin Chang, Mei-Chin Mong, Ya-Chen Yang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai Jun 2024

Contribution Of Matrix Metalloproteinase-2 And Matrix Metalloproteinase-9 To Upper Tract Urothelial Cancer Risk In Taiwan, Bo-Ren Wang, Hung-Huan Ma, Chao-Hsiang Chang, Cheng-Hsi Liao, Wen-Shin Chang, Mei-Chin Mong, Ya-Chen Yang, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were …


Aerobic And Anaerobic Exercise's Impact On Cognitive Functions In Eighth Grade Students., Heather Erwin, Sarah Schreiber Jun 2024

Aerobic And Anaerobic Exercise's Impact On Cognitive Functions In Eighth Grade Students., Heather Erwin, Sarah Schreiber

Kinesiology and Health Promotion Faculty Publications

The present study examined the impact of aerobic and anaerobic exercise on cognitive abilities in eighth grade students at one middle school in southeastern US. It is known that youth do not meet recommended physical activity levels, yet there is research demonstrating a clear connection between aerobic exercise and academic performance. There is a gap in evidence regarding anaerobic exercise and cognitive capabilities. If professionals know which type of exercise is most beneficial for enhancing cognition in youth, it will behoove them to incorporate these practices in physical education and other areas throughout the school day for students. Thus, this …


Cross-Sectional Analysis Of The Association Between Household Food Insecurity And Mental Health Conditions In Children Aged 5–11 Years In Canada, Justin Thielman, Sarah Orr, Saranya Naraentheraraja, Daniel Harrington, Sarah Carsley Jun 2024

Cross-Sectional Analysis Of The Association Between Household Food Insecurity And Mental Health Conditions In Children Aged 5–11 Years In Canada, Justin Thielman, Sarah Orr, Saranya Naraentheraraja, Daniel Harrington, Sarah Carsley

Faculty, Staff and Student Publications

BACKGROUND: Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of food insecurity and diagnosed mental health conditions in young children remains unknown. This study examined the association between household food insecurity and reported diagnosed mental health conditions among children aged 5-11 years in Canada.

METHODS: This study included 16 216 children aged 5-11 years living in Canada, from the 2019 Canadian Health Survey on Children and Youth. We measured household food insecurity using the Household Food Security Survey Module. We measured diagnosed mental health conditions by …


Car T-Cell Expansion: Harmful Or Helpful?, Anath C Lionel, Sattva S Neelapu Jun 2024

Car T-Cell Expansion: Harmful Or Helpful?, Anath C Lionel, Sattva S Neelapu

Faculty, Staff and Student Publications

No abstract provided.


Hypoxia Inducible Factor 2Α Promotes Tolerogenic Macrophage Development During Cardiac Transplantation Through Transcriptional Regulation Of Colony Stimulating Factor 1 Receptor, Matthew Deberge, Samantha Schroth, Fanfan Du, Xin Yi Yeap, Jiao-Jing Wang, Zheng Jenny Zhang, Mohammed Javeed Ansari, Evan A Scott, Edward B Thorp Jun 2024

Hypoxia Inducible Factor 2Α Promotes Tolerogenic Macrophage Development During Cardiac Transplantation Through Transcriptional Regulation Of Colony Stimulating Factor 1 Receptor, Matthew Deberge, Samantha Schroth, Fanfan Du, Xin Yi Yeap, Jiao-Jing Wang, Zheng Jenny Zhang, Mohammed Javeed Ansari, Evan A Scott, Edward B Thorp

Faculty, Staff and Student Publications

Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, myeloid cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state of transplantation tolerance. Transplantation tolerance holds promise to reduce complications from chronic immunosuppression and promote long-term survival in transplant recipients. We sought to identify different mediators of transplantation tolerance by performing single-cell RNA sequencing of acute rejecting or tolerized cardiac allografts. This led to the unbiased identification of the transcription factor, hypoxia inducible factor (HIF)-2α, in a subset of tolerogenic monocytes. Using flow cytometric analyses and mice …


Cracd Loss Induces Neuroendocrine Cell Plasticity Of Lung Adenocarcinoma, Bongjun Kim, Shengzhe Zhang, Yuanjian Huang, Kyung-Pil Ko, Youn-Sang Jung, Jinho Jang, Gengyi Zou, Jie Zhang, Sohee Jun, Kee-Beom Kim, Kwon-Sik Park, Jae-Il Park Jun 2024

Cracd Loss Induces Neuroendocrine Cell Plasticity Of Lung Adenocarcinoma, Bongjun Kim, Shengzhe Zhang, Yuanjian Huang, Kyung-Pil Ko, Youn-Sang Jung, Jinho Jang, Gengyi Zou, Jie Zhang, Sohee Jun, Kee-Beom Kim, Kwon-Sik Park, Jae-Il Park

Faculty, Staff and Student Publications

Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD (capping protein inhibiting regulator of actin dynamics), a capping protein inhibitor, is frequently inactivated in cancers. CRACD knockout (KO) is sufficient to de-repress NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE cell plasticity is associated with cell de-differentiation and stemness-related pathway activation. The …


A Spatiotemporal Map Of Co-Receptor Signaling Networks Underlying B Cell Activation, Katherine J Susa, Gary A Bradshaw, Robyn J Eisert, Charlotte M Schilling, Marian Kalocsay, Stephen C Blacklow, Andrew C Kruse Jun 2024

A Spatiotemporal Map Of Co-Receptor Signaling Networks Underlying B Cell Activation, Katherine J Susa, Gary A Bradshaw, Robyn J Eisert, Charlotte M Schilling, Marian Kalocsay, Stephen C Blacklow, Andrew C Kruse

Faculty, Staff and Student Publications

The B cell receptor (BCR) signals together with a multi-component co-receptor complex to initiate B cell activation in response to antigen binding. Here, we take advantage of peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track co-receptor signaling dynamics in Raji cells from 10 s to 2 h after BCR stimulation. This approach enables tracking of 2,814 proximity-labeled proteins and 1,394 phosphosites and provides an unbiased and quantitative molecular map of proteins recruited to the vicinity of CD19, the signaling subunit of the co-receptor complex. We detail the recruitment kinetics of signaling effectors to CD19 and identify previously uncharacterized …


A Harmonized Public Resource Of Deeply Sequenced Diverse Human Genomes, Zan Koenig, Mary T Yohannes, Lethukuthula L Nkambule, Xuefang Zhao, Julia K Goodrich, Heesu Ally Kim, Michael W Wilson, Grace Tiao, Stephanie P Hao, Nareh Sahakian, Katherine R Chao, Mark A Walker, Yunfei Lyu, Heidi L Rehm, Benjamin M Neale, Michael E Talkowski, Mark J Daly, Harrison Brand, Konrad J Karczewski, Elizabeth G Atkinson, Alicia R Martin Jun 2024

A Harmonized Public Resource Of Deeply Sequenced Diverse Human Genomes, Zan Koenig, Mary T Yohannes, Lethukuthula L Nkambule, Xuefang Zhao, Julia K Goodrich, Heesu Ally Kim, Michael W Wilson, Grace Tiao, Stephanie P Hao, Nareh Sahakian, Katherine R Chao, Mark A Walker, Yunfei Lyu, Heidi L Rehm, Benjamin M Neale, Michael E Talkowski, Mark J Daly, Harrison Brand, Konrad J Karczewski, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, …


A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors, Jie Yang, Joel Cassel, Brian C Boyle, Daniel Oppong, Young-Hoon Ahn, Brian P Weiser Jun 2024

A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors, Jie Yang, Joel Cassel, Brian C Boyle, Daniel Oppong, Young-Hoon Ahn, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Human sirtuin-2 (SIRT2) has emerged as an attractive drug target for a variety of diseases. The enzyme is a deacylase that can remove chemically different acyl modifications from protein lysine residues. Here, we developed a high-throughput screen based on a homogeneous time-resolved fluorescence (HTRF) binding assay to identify inhibitors of SIRT2's demyristoylase activity, which is uncommon among many ligands that only affect its deacetylase activity. From a test screen of 9600 compounds, we identified a small molecule that inhibited SIRT2's deacetylase activity (IC50 = 7 μM) as well as its demyristoylase activity (IC50 = 37 μM). The inhibitor was composed …


06.24.2024 Orsp Connect, Liz Williamson Jun 2024

06.24.2024 Orsp Connect, Liz Williamson

ORED Newsletter

Research Networking Lunch (LINC), NIH podcast, CREW (Community First Research Center for Wellbeing and Creative Achievement) Premier Physics Experiment


An Improved Method For Diagnosis Of Parkinson’S Disease Using Deep Learning Models Enhanced With Metaheuristic Algorithm, Babita Majhi, Aarti Kashyap, Siddhartha Suprasad Mohanty, Sujata Dash, Saurav Mallik, Aimin Li, Zhongming Zhao Jun 2024

An Improved Method For Diagnosis Of Parkinson’S Disease Using Deep Learning Models Enhanced With Metaheuristic Algorithm, Babita Majhi, Aarti Kashyap, Siddhartha Suprasad Mohanty, Sujata Dash, Saurav Mallik, Aimin Li, Zhongming Zhao

Faculty, Staff and Student Publications

Parkinson's disease (PD) is challenging for clinicians to accurately diagnose in the early stages. Quantitative measures of brain health can be obtained safely and non-invasively using medical imaging techniques like magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). For accurate diagnosis of PD, powerful machine learning and deep learning models as well as the effectiveness of medical imaging tools for assessing neurological health are required. This study proposes four deep learning models with a hybrid model for the early detection of PD. For the simulation study, two standard datasets are chosen. Further to improve the performance of …


Integration Of Electrospun Scaffolds And Biological Polymers For Enhancing The Delivery And Efficacy Of Mesenchymal Stem/Stromal Cell Therapies, Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon Jun 2024

Integration Of Electrospun Scaffolds And Biological Polymers For Enhancing The Delivery And Efficacy Of Mesenchymal Stem/Stromal Cell Therapies, Allan John R Barcena, Archana Mishra, Dominic Karl M Bolinas, Benjamin M Martin, Marites P Melancon

Faculty, Staff and Student Publications

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity …


Methphaser: Methylation-Based Long-Read Haplotype Phasing Of Human Genomes, Yilei Fu, Sergey Aganezov, Medhat Mahmoud, John Beaulaurier, Sissel Juul, Todd J Treangen, Fritz J Sedlazeck Jun 2024

Methphaser: Methylation-Based Long-Read Haplotype Phasing Of Human Genomes, Yilei Fu, Sergey Aganezov, Medhat Mahmoud, John Beaulaurier, Sissel Juul, Todd J Treangen, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The assignment of variants across haplotypes, phasing, is crucial for predicting the consequences, interaction, and inheritance of mutations and is a key step in improving our understanding of phenotype and disease. However, phasing is limited by read length and stretches of homozygosity along the genome. To overcome this limitation, we designed MethPhaser, a method that utilizes methylation signals from Oxford Nanopore Technologies to extend Single Nucleotide Variation (SNV)-based phasing. We demonstrate that haplotype-specific methylations extensively exist in Human genomes and the advent of long-read technologies enabled direct report of methylation signals. For ONT R9 and R10 cell line data, we …


Exploring The Mechanistic Trail Connecting Cellular Function, Health, And Athletic Performance With Phase Angle: A Review On The Physiology Of Phase Angle And Exercise-Based Interventions, Trevor Short, Paulette Yamada Jun 2024

Exploring The Mechanistic Trail Connecting Cellular Function, Health, And Athletic Performance With Phase Angle: A Review On The Physiology Of Phase Angle And Exercise-Based Interventions, Trevor Short, Paulette Yamada

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 5: Issue 1, Article 7, 2024. Bioelectrical impedance analysis-derived phase angle (PhA) has been widely used in clinical and sports settings, as it is positively associated with health and fitness. However, what PhA is measuring at the cellular level has not been addressed, which limits our interpretation of PhA. The purpose of this review is to provide a roadmap, starting with the mechanistic link between the dielectric properties of mammalian cells and their physiological function. In simplistic terms, PhA measures cellular permittivity and electrical conductivity. These characteristics determine cellular health and function. This …


A Cocktail Nanovaccine Targeting Key Entry Glycoproteins Elicits High Neutralizing Antibody Levels Against Ebv Infection., Ling Zhong, Wanlin Zhang, Hong Liu, Xinyu Zhang, Zeyu Yang, Zhenfu Wen, Ling Chen, Haolin Chen, Yanran Luo, Yanhong Chen, Qisheng Feng, Mu-Sheng Zeng, Qinjian Zhao, Lixin Liu, Claude Krummenacher, Yi-Xin Zeng, Yongming Chen, Miao Xu, Xiao Zhang Jun 2024

A Cocktail Nanovaccine Targeting Key Entry Glycoproteins Elicits High Neutralizing Antibody Levels Against Ebv Infection., Ling Zhong, Wanlin Zhang, Hong Liu, Xinyu Zhang, Zeyu Yang, Zhenfu Wen, Ling Chen, Haolin Chen, Yanran Luo, Yanhong Chen, Qisheng Feng, Mu-Sheng Zeng, Qinjian Zhao, Lixin Liu, Claude Krummenacher, Yi-Xin Zeng, Yongming Chen, Miao Xu, Xiao Zhang

College of Science & Mathematics Departmental Research

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient …


Pathways To Therapy Resistance: The Sheltering Effect Of The Bone Marrow Microenvironment To Multiple Myeloma Cells, Kuntal Bhowmick, Max Von Suskil, Omar Al-Odat, Weam Othman Elbezanti, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K. Pandey Jun 2024

Pathways To Therapy Resistance: The Sheltering Effect Of The Bone Marrow Microenvironment To Multiple Myeloma Cells, Kuntal Bhowmick, Max Von Suskil, Omar Al-Odat, Weam Othman Elbezanti, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K. Pandey

College of Science & Mathematics Departmental Research

Multiple Myeloma (MM) is a malignant expansion of plasma cells in the bone marrow (BM), resulting in a disease characterized by symptoms of end organ damage from light chain secretion, crowding of the BM, and bone lesions. Although the past two decades have been characterized by numerous novel therapies emerging, the disease remains incurable due to intrinsic or acquired drug resistance. A major player in MM's drug resistance arises from its intimate relationship with the BM microenvironment (BMME). Through stress-inducing conditions, soluble messengers, and physical adhesion to BM elements, the BMME activates numerous pathways in the myeloma cell. This not …


The Relationship Between Medication Beliefs, Patient Activation, And Self-Rated Health In Patients Taking Oral Anticancer Agents, Misun Hwang, Youmin Cho, Yang Gong, Yun Jiang Jun 2024

The Relationship Between Medication Beliefs, Patient Activation, And Self-Rated Health In Patients Taking Oral Anticancer Agents, Misun Hwang, Youmin Cho, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH.

Methods: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, …


Discovery Of Runs-Of-Homozygosity Diplotype Clusters And Their Associations With Diseases In Uk Biobank, Ardalan Naseri, Degui Zhi, Shaojie Zhang Jun 2024

Discovery Of Runs-Of-Homozygosity Diplotype Clusters And Their Associations With Diseases In Uk Biobank, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

Runs-of-homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE (runs-of-homozygous diplotype cluster enumerator), to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number …


Novel Adaptations In Iron Regulation Acquired During Chronic Fungal Cf Infections, Daniel R. Murante Jun 2024

Novel Adaptations In Iron Regulation Acquired During Chronic Fungal Cf Infections, Daniel R. Murante

Dartmouth College Ph.D Dissertations

Chronic fungal infections are highly recalcitrant to treatment; we postulated that as populations persist, increasing genetic diversity is reflected in phenotypic heterogeneity, contributing to treatment inefficacies. The study of evolutionary patterns is underrepresented in chronic fungal infections, and to supplement this body of knowledge, we leveraged isolates acquired from four individuals with chronic fungal-dominated cystic fibrosis infections. We evaluated in-host evolution through a whole-genome sequencing approach, comparing multiple isolates obtained from each subject's sputum and bronchoalveolar lavage fluid. Our analysis found non-synonymous mutations that arose in parallel across the independent infections in the gene MRS4, which encodes a mitochondrial …


Multiple Omics Levels Of Chronic Lymphocytic Leukemia, Aleksander Turk, Eva Čeh, George A Calin, Tanja Kunej Jun 2024

Multiple Omics Levels Of Chronic Lymphocytic Leukemia, Aleksander Turk, Eva Čeh, George A Calin, Tanja Kunej

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy characterized by the proliferation of functionally mature but incompetent B cells. It is the most prevalent type of leukemia in Western populations, accounting for approximately 25% of new leukemia cases. While recent advances, such as ibrutinib and venetoclax treatment have improved patient outlook, aggressive forms of CLL such as Richter transformation still pose a significant challenge. This discrepancy may be due to the heterogeneity of factors contributing to CLL development at multiple -omics levels. However, information on the omics of CLL is fragmented, hindering multi-omics-based research into potential treatment options. To address …


Study Of Prognostic Splicing Factors In Cancer Using Machine Learning Approaches, Mengyuan Yang, Jiajia Liu, Pora Kim, Xiaobo Zhou Jun 2024

Study Of Prognostic Splicing Factors In Cancer Using Machine Learning Approaches, Mengyuan Yang, Jiajia Liu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal …


Protocol For Seahorse Analysis Of Ex Vivo Mouse Brown And White Adipose Tissues, Fenfen Wang, Phu M Huynh, Yu A An Jun 2024

Protocol For Seahorse Analysis Of Ex Vivo Mouse Brown And White Adipose Tissues, Fenfen Wang, Phu M Huynh, Yu A An

Faculty, Staff and Student Publications

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.


Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen Jun 2024

Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated …


Association Between Obstructive Sleep Apnea And Risk Of Benign Vocal Fold Lesions: A Nationwide 9-Year Follow-Up Cohort Study, Yong Tae Hong, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Seung Kim Jun 2024

Association Between Obstructive Sleep Apnea And Risk Of Benign Vocal Fold Lesions: A Nationwide 9-Year Follow-Up Cohort Study, Yong Tae Hong, Min Gu Kang, Min Gyu Lee, Sang Woo Yeom, Jong Seung Kim

Faculty, Staff and Student Publications

Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association …