Digital Commons Network^™

Ablation Of The Integrin Cd11b Mac-1 Limits Deleterious Responses To Traumatic Spinal Cord Injury And Improves Functional Recovery In Mice, Yun Li, Zhuofan Lei, Rodney M Ritzel, Junyun He, Simon Liu, Li Zhang, Junfang Wu

Faculty, Staff and Student Publications

Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of

Tumor-Infiltrating Nerves Functionally Alter Brain Circuits And Modulate Behavior In A Mouse Model Of Head-And-Neck Cancer, Jeffrey Barr, Austin Walz, Anthony C Restaino, Moran Amit, Sarah M Barclay, Elisabeth G Vichaya, William C Spanos, Robert Dantzer, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer and neuronal tracing, we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons decreased …

Protocol For The Derivation Of Primary Cancer Stem Cell Lines From Human Ependymal Tumors, Cory M Richman, Peter B Dirks, Michael D Taylor, Kulandaimanuvel Antony Michealraj

Faculty, Staff and Students Publications

Cancer stem cells (CSCs) established from surgical biopsies closely mimic the human context and can be used to investigate disease mechanisms, genetic fitness, and therapeutic evaluation. Here, we present a protocol for the derivation of primary patient-derived CSC lines from ependymal tumors. We describe the necessary steps, from surgical intervention and biopsy to the dissociation of ependymomas to derive cultures. We then detail procedures for cell line propagation and define the characteristics of these primary cancer cell lines. For complete details on the use and execution of this protocol, please refer to Michealraj et al.

Optimization Of Cellular Transduction By The Hiv-Based Pseudovirus Platform With Pan-Coronavirus Spike Proteins, Syamala Rani Thimmiraju, Maria Jose Villar, Jason T Kimata, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has …

The P-Myh9/Usp22/Hif-1Α Axis Promotes Lenvatinib Resistance And Cancer Stemness In Hepatocellular Carcinoma, Qiaonan Shan, Lu Yin, Qifan Zhan, Jiongjie Yu, Sheng Pan, Jianyong Zhuo, Wei Zhou, Jiaqi Bao, Lincheng Zhang, Jiachen Hong, Jianan Xiang, Qingyang Que, Kangchen Chen, Shengjun Xu, Jingrui Wang, Yangbo Zhu, Bin He, Jingbang Wu, Haiyang Xie, Shusen Zheng, Tingting Feng, Sunbin Ling, Xiao Xu

Faculty, Staff and Student Publications

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples …

A Holistic Approach To Music For Stress Management During Pregnancy, Danielle Emily Dixon

Doctoral Dissertations and Projects

Pregnancy is a transformative journey for women, but amidst the excitement and anticipation that most women experience, pregnancy often raises stress levels to profound heights for various reasons, which may include hormonal fluctuations, physical discomforts, concerns about the baby’s health, financial pressures, relationship changes, fear of labor and birth, life adjustments, and societal expectations. The purpose of this qualitative hermeneutic phenomenological study was to examine how music interventions impacted stress levels during pregnancy. This two-week study employed an in-person group experiment involving pregnant women. The study sample was selected via voluntary response sampling, where pregnant women volunteered to participate in …

Adaptation Of The Socioecological Model To Address Disparities In Engagement Of Black Men In Prostate Cancer Genetic Testing, Amy Leader, Timothy Rebbeck, William Oh, Alpa Patel, Eric Winer, Leeann Bailey, Leonard Gomella, Crystal Lumpkins, Isla Garraway, Lisa Aiello, Monica Baskin, Heather H Cheng, Kathleen Cooney, Amanda Ganzak, Daniel George, Susan Halabi, Feighanne Hathaway, Claire Healy, Joseph W Kim, Michael Leapman, Stacy Loeb, Kara Maxwell, Christopher Mcnair, Todd Morgan, Breanne Prindeville, Howard R Soule, Whitney Steward, Sakinah Suttiratana, Mary-Ellen Taplin, Kosj Yamoah, Thierry Fortune, Kris Bennett, Joshua Blanding-Godbolt, Laura Gross, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT.

METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa …

Trends In Pediatric Opioid Prescribing And Use, Robert W. Steele, Michelle Dephillips

Pediatrics in Practice: A CME Podcast

In this episode, Dr. Michelle DePhillips leads a discussion focusing on the rising trend in opioid prescribing, and its effects on global health.

Click here to stream the podcast episode.

The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy Through Tfeb, Mckenna Losby, Matthew Hayes, Aurore Valfort, Danesh H Sopariwala, Ryan Sanders, John K Walker, Weiyi Xu, Vihang A Narkar, Lilei Zhang, Cyrielle Billon, Thomas P Burris

Faculty, Staff and Students Publications

Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) are fundamental in regulating cardiac metabolism and function. Previously, we showed that ERR agonists improve cardiac function in models of heart failure and induce autophagy. Here, we characterized a mechanism by which ERRs induce the autophagy pathway in cardiomyocytes. Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway and has been shown to be crucial regulator of genes that control autophagy. We discovered that TFEB is a direct ERR target gene whose expression is induced by ERR agonists. Activation of …

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment As A Therapeutic Target In A Mouse Model Of Lung Cancer, Sean-Luc Shanahan, Nikesh Kunder, Charles Inaku, Natalie B Hagan, Grace Gibbons, Nicolas Mathey-Andrews, Gayathri Anandappa, Shawn Soares, Kristen E Pauken, Tyler Jacks, Jason M Schenkel

Faculty, Staff and Student Publications

Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer …

Impact And Characterization Of Serial Structural Variations Across Humans And Great Apes, Wolfram Höps, Tobias Rausch, Michael Jendrusch, Jan O Korbel, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series of mutations, a phenomenon we refer to as serial SV (sSV), remain underexplored, posing a challenge for SV discovery. Here, we present NAHRwhals ( https://github.com/WHops/NAHRwhals ), a method to infer repeat-mediated series of SVs in long-read genomic assemblies. Applying NAHRwhals to haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci of various length and complexity. These sSVs explain otherwise cryptic variation in medically relevant regions such as the TPSAB1 gene, 8p23.1, 22q11 and Sotos syndrome regions. Comparisons …

Understanding Hip Pain Through Social Media: An Initial Overview Of An International Web-Based Survey, John M. Gaddis, Ryan Bialaszewski, Bretton Laboret, Erika Shults, Joel Wells

Research Colloquium

Aims: In the adult population hip pain is often triggered by mechanical anatomic differences including hip dysplasia, femoroacetabular impingement (FAI), Perthes disease and osteoarthritis. We aimed to understand the adult experience of hip pain and develop a comprehensive hip-pain survey using a web-based REDCap platform via social media. This paper outlines our survey and analyzes the demographic composition and characteristics of our sample population.

Methods: The survey link was active from October 1, 2023, to May 1, 2024, on social media platforms. Respondents consented to the study before beginning. Responses were anonymous and only unique surveys were analyzed. The comprehensive …

Periacetabular Osteotomy: An Analysis Of Social Media To Determine The Most Common Questions Asked By The Periacetabular Osteotomy Population, John M. Gaddis, Ryan Bialaszewski, Bretton Laboret, Joel Wells, Adina Stewart

Research Colloquium

Background: Social media has become an increasingly popular resource for patients and a platform to share one’s experiences. Patients undergoing periacetabular osteotomy (PAO) may gravitate towards social media for support, guidance and understanding. The aim of this study was to investigate Facebook, Instagram and Twitter to further understand what the most common preoperative and postoperative questions patients undergoing PAO are asking.

Methods: Facebook, Instagram and Twitter were queried consecutively from February 1, 2023 to November 23, 2011. Facebook was searched for the two most populated interest groups; “Periacetabular Osteotomy (PAO)” and “Periacetabular Osteotomy Australia”. Instagram and Twitter were queried for …

Mouse Monocytes Express Cd127 By Immune Cells, Not Lps, Reza Yazdani, Mozhde Askari, Amir Moghadam-Ahmadi, Gholamreza Azizi, Bogoljub Ciric, Alexandra Boehm, Guang-Xian Zhang, Mohamad Rostami

Department of Neurology Faculty Papers

The essential role of interleukin 7 (IL-7) signaling via its receptor (IL-7Rα; CD127) in T cell development and function has been well documented. However, CD127 expression and function in myeloid cells, including monocytes, are less clear, especially in mice. In the present study we report an inducible CD127 expression in mouse monocytes/macrophages. This induction is dependent on the presence of other immune cells, highlighting that regulation of CD127 expression on monocytes differs in mice and humans. We demonstrate that CD127 is functional, as IL-7 downregulated its expression. We also saw decreased CD127 expression during inflammation in vivo. Overall, upregulation …

Role Of Poly(A)-Binding Protein Cytoplasmic 1, A Trna-Derived Rna Fragment-Bound Protein, In Respiratory Syncytial Virus Infection, Devin V Davis, Eun-Jin Choi, Deena Ismail, Miranda L Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host-RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5'-end of …

Characterization Of Dna Damage Repair Pathway Utilization In High-Grade Serous Ovarian Cancers Yields Rational Therapeutic Approaches, Erika Nakatsuka, Lijun Tan, Brianna Cunneen, Caroline Foster, Yu Leo Lei, Karen Mclean

Faculty, Staff and Student Publications

While poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have improved the prognosis of ovarian high-grade serous carcinoma (HGSC) tumors that are homologous recombination (HR) deficient (HRD), new therapeutic strategies are needed for tumors that are HR proficient (HRP) because they demonstrate greater resistance to current treatments and thus have poorer clinical outcomes. Additionally, clinical precautionary statements regarding potential risks associated with PARPi, such as myelodysplastic syndrome, highlight the need for combinatorial approaches that can lessen the dose and duration of PARPi treatment to reduce toxicities. Here, we evaluated DNA double-strand damage repair pathways in HRD and HRP ovarian cancer cell lines …

Persistent Tailoring Of Msc Activation Through Genetic Priming, Michael A Beauregard, Guy C Bedford, Daniel A Brenner, Leonardo D Sanchez Solis, Tomoki Nishiguchi, Abhimanyu, Santiago Carrero Longlax, Barun Mahata, Omid Veiseh, Pamela L Wenzel, Andrew R Dinardo, Isaac B Hilton, Michael R Diehl

Faculty, Staff and Student Publications

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce the expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a genetic priming method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor interferon response factor 1 (IRF1). MSCs engineered to …

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. …

Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon

Faculty, Staff and Students Publications

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated …

Use Of Web-Based Surveys To Collect Long-Term Pediatric Outcomes In Patients With Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation: Observational Study, Eric Bergh, Kimberly Rennie, Jimmy Espinoza, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost.

Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS.

Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during …

Batf Is A Major Driver Of Nk Cell Epigenetic Reprogramming And Dysfunction In Aml, Bijender Kumar, Anand Singh, Rafet Basar, Nadima Uprety, Ye Li, Huihui Fan, Ana Karen Nunez Cortes, Mecit Kaplan, Sunil Acharya, Hila Shaim, Anna C Xu, Manrong Wu, Emily Ensley, Dexing Fang, Pinaki P Banerjee, Luciana Melo Garcia, Silvia Tiberti, Paul Lin, Hind Rafei, Maliha Nuzhat Munir, Madison Moore, Mayra Shanley, Mayela Mendt, Lucila N Kerbauy, Bin Liu, Alexander Biederstädt, Elif Gokdemir, Susmita Ghosh, Kiran Kundu, Francia Reyes-Silva, Xin Ru Jiang, Xinhai Wan, April L Gilbert, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Patrick Zhang, Enli Liu, Luis Muniz-Feliciano, Gary M Deyter, Abhinav K Jain, Juan Jose Rodriguez-Sevilla, Simona Colla, Guillermo Garcia-Manero, Elizabeth J Shpall, Ken Chen, Hussein A Abbas, Kunal Rai, Katayoun Rezvani, May Daher

Faculty, Staff and Student Publications

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism and exhausted phenotype at the single cell transcriptomic and proteomic levels. In this study we identified that this dysfunction was mediated through a crosstalk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ integrin/TGF-β/SMAD pathway but, once established, was persistent due to profound epigenetic reprogramming. …

Bacteroides Ovatus Alleviates Dysbiotic Microbiota-Induced Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C Stinson, Mohamed A Jamal, Miriam R Ortega, Christopher A Sanchez, Saira S Ahmed, Jennifer L Karmouch, Chia-Chi Chang, Ivonne I Flores, Lauren K Mcdaniel, Alexandria N Brown, Rawan K El-Himri, Valerie A Chapa, Lin Tan, Bao Q Tran, Yao Xiao, Christopher Fan, Dung Pham, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Israel K Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y King, Robert A Britton, Pavan Reddy, Matthew C Wong, Nadim J Ajami, Jennifer A Wargo, Samuel Shelburne, Pablo C Okhuysen, Chen Liu, Stephanie W Fowler, Margaret E Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos Da Silva, Doris M Ponce, Jonathan U Peled, Marcel R M Van Den Brink, Christine B Peterson, Gabriela Rondon, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Philip L Lorenzi, Rohtesh S Mehta, Eric C Martens, Amin M Alousi, Robert R Jenq

Faculty, Staff and Student Publications

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects …

Evaluation Of The Influence Of Training In An Immersive Virtual Reality Environment On Sports Skills In Table Tennis, Martin Škopek, Josef Heidler, Štefan Balkó, Lenka Vojtíková, Radka Ulrichová

Baltic Journal of Health and Physical Activity

Introduction: This study explores the possibilities of leveraging immersive virtual reality (VR) training for the improvement of table tennis skills. The primary objective was to assess the in-fluence of VR intervention on the development of table tennis skills. Materials and Methods: Thirty-eight participants, whose mean age was 17.37 ± 0.84 years and who lacked previous table tennis experience, were divided into experimental (n = 21) and control (n = 17) groups. The experimental group engaged in six sessions of VR training aimed at enhancing table tennis skills, and their performance was evaluated using a comprehensive test battery. In contrast, the …

Mitochondrial Reprogramming By Activating Oxphos Via Glutamine Metabolism In African American Patients With Bladder Cancer, Karthik Reddy Kami Reddy, Danthasinghe Waduge Badrajee Piyarathna, Jun Hyoung Park, Vasanta Putluri, Chandra Sekhar Amara, Abu Hena Mostafa Kamal, Jun Xu, Daniel Kraushaar, Shixia Huang, Sung Yun Jung, Livia S Eberlin, Jabril R Johnson, Rick A Kittles, Leomar Y Ballester, Krishna Parsawar, M Minhaj Siddiqui, Jianjun Gao, Adriana Langer Gramer, Roni J Bollag, Martha K Terris, Yair Lotan, Chad J Creighton, Seth P Lerner, Arun Sreekumar, Benny Abraham Kaipparettu, Nagireddy Putluri

Faculty, Staff and Students Publications

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further …

Transcriptomic And Proteomic Differences In Btk-Wt And Btk-Mutated Cll And Their Changes During Therapy With Pirtobrutinib, Burcu Aslan, Ganiraju Manyam, Lakesla R Iles, Shady I Tantawy, Sai Prasad Desikan, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Covalent Bruton tyrosine kinase inhibitors (cBTKis), which bind to the BTK C481 residue, are now primary therapeutics for chronic lymphocytic leukemia (CLL). Alterations at C481, primarily C481S, prevent cBTKi binding and lead to the emergence of resistant clones. Pirtobrutinib is a noncovalent BTKi that binds to both wild-type (WT) and C481S-mutated BTK and has shown efficacy in BTK-WT and -mutated CLL patient groups. To compare baseline clinical, transcriptomic, and proteomic characteristics and their changes during treatment in these 2 groups, we used 67 longitudinal peripheral blood samples obtained during the first 3 cycles of treatment with pirtobrutinib from 18 patients …

Sensory Dysfunction, Microbial Infections, And Host Responses In Alzheimer's Disease, Praveen Bathini, Emanuele Brai, Brian J Balin, Lynn Bimler, David B Corry, Davangere P Devanand, Richard L Doty, Garth D Ehrlich, William A Eimer, Tamas Fulop, David L Hahn, Christine J Hammond, Joseph Infanti, Ruth Itzhaki, Richard Lathe, Christopher Scott Little, Rima Mcleod, Shima T Moein, Amy R Nelson, George Perry, Or A Shemesh, Rudolph E Tanzi, Wilmore C Webley, Nikki M Schultek, Lavinia Alberi Auber

Faculty, Staff and Students Publications

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways …

Cardiomyocyte-Derived Small Extracellular Vesicle: A New Mechanism Driving Diabetic Cardiac Fibrosis And Cardiomyopathy, Yu Li, Yunhui Du, Yang Liu, Xiuhuan Chen, Xinxin Li, Yanru Duan, Yanwen Qin, Huirong Liu, Xinliang Ma, Shaoping Nie, Huina Zhang

Department of Emergency Medicine Faculty Papers

Rationale: Diabetic cardiomyopathy is one of the major diabetic cardiovascular complications in which fibrosis plays a critical pathogenetic role. However, the precise mechanisms by which diabetes triggers cardiac fibrosis in the heart remain elusive. Small extracellular vesicles (sEVs) play an important role in the cellular communication. Nevertheless, whether and how diabetes may adversely alter sEVs-mediated cardiomyocyte-fibroblast communication, promoting diabetic cardiac fibrosis and contributing to diabetic cardiomyopathy, has not been previously investigated. Methods and results: High-fat diet (HFD)-induced and genetic (db/db) type 2 diabetic models were utilized. Cardiomyocyte sEVs (Myo-sEVs) were isolated by ultracentrifugation. Normal cardiomyocyte-derived Myo-sEVs attenuated diabetic cardiac fibrosis …

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 …

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 …