Digital Commons Network^™

The Relationship Between Physical Activity And Telomere Length In Women: A Systematic Review, Jeni Page, Catherine Stephens, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A …

The Impact Of Atlas Parcellation On Functional Connectivity Analysis Across Six Psychiatric Disorders, Xiaoya Wu, Chuang Liang, Juan Bustillo, Peter Kochunov, Xuyun Wen, Jing Sui, Rongtao Jiang, Xiao Yang, Zening Fu, Daoqiang Zhang, Vince D Calhoun, Shile Qi

Faculty, Staff and Student Publications

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, …

Uric Acid Stroke Cerebroprotection Transcended Sex, Age, And Comorbidities In A Multicenter Preclinical Trial, Rakesh B Patel, Mariia Kumskova, Hanish Kodali, Ivan Budnik, Vitalii Kuznetsov, Aditi Jain, Abhishek Jha, Daniel Thedens, Nirav Dhanesha, Brijesh Sutariya, Karisma A Nagarkatti, Jessica Lamb, Pradip Kamat, Yanrong Shi, Brooklyn Avery, Takahiko Imai, Xuyan Jin, Anjali Chauhan, Ligia S B Boisserand, Mohammad B Khan, Krishnan Dhandapani, Basavaraju G Sanganahalli, Lauren H Sansing, David C Hess, Raymond C Koehler, Louise D Mccullough, Jaroslaw Aronowski, Cenk Ayata, Márcio A Diniz, Patrick D Lyden, Anna M Planas, Angel Chamorro, Anil K Chauhan, Enrique C Leira, Span Investigators

Faculty, Staff and Student Publications

Background: Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.

Methods: We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered …

Opportunities In Stroke Care At Safety Net Hospitals: A Socioecological Perspective, Anjail Sharrief, Joshua Wollen, Maha Almohamad, M Carter Denny, Erica Jones, Aardhra M Venkatachalam, Digvijaya Navalkele, Shivika Chandra, Mariam Ahmed, Robert Pratt, Bradley D Shy, John Mcmenamy, Chigozirim Izeogu, Lesli E Skolarus, Nneka L Ifejika, Nicole R Gonzales

Faculty, Staff and Student Publications

Safety net hospitals (SNHs) provide care to patients regardless of their insurance status or ability to pay, serving populations at the highest risk for poor stroke outcomes. These include historically marginalized racial and ethnic groups, and individuals disproportionately affected by adverse social drivers of health, including lower socioeconomic status, housing instability, and limited access to preventive care. Improving stroke care at SNHs presents a critical opportunity to strengthen care delivery for individuals with the greatest need. However, such efforts require a clear understanding of the barriers across all levels of the healthcare system. In this Perspective, the authors adopt a …

Acute Pain Trajectories In Elderly Patients With Fragility Hip Fractures, Paul Potnuru, Christina Goehl, Katherine S Becker, Alejandro Juul, Madison Aycock, Johanna Blair De Haan, Sudipta Sen, Michelle Ge, Stephen J Warner, Nadia Hernandez

Faculty, Staff and Student Publications

Background: Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.

Methods: We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Crispr/Cas9 Gene Therapy Increases The Risk Of Tumorigenesis In The Mouse Model Of Hereditary Tyrosinemia Type I, Tong Chen, Mercedes Barzi, Nika Furey, Hyunjae R Kim, Francis P Pankowicz, Xavier Legras, Sara H Elsea, Ayrea E Hurley, Diane Yang, David A Wheeler, Malgorzata Borowiak, Beatrice Bissig-Choisat, Pavel Sumazin, Karl-Dimiter Bissig

Center for Medical Ethics and Health Policy Staff Publications

Background & aims: The therapeutic potential of CRISPR gene editing has been demonstrated in various animal models; however, little is known about its long-term consequences. This study seeks to bridge this gap by investigating the lasting consequences of CRISPR gene therapy in an animal model of hereditary tyrosinemia type I (HT-I). We compared the standard of care-nitisinone, a small molecule inhibitor of hydroxyphenylpyruvate dioxygenase (HPD)-with the deletion of the Hpd gene by CRISPR gene therapy. Both treatments block flux through tyrosine catabolism and thereby prevent the accumulation of toxic catabolites in HT-I.

Methods: We assessed the efficacy and safety of …

Otolith And Genomic Data Reveal Temporal Insights Into Stocking Across A Large River Basin In A Mobile, Long-Lived Australian Freshwater Fish Species, Katherine A Harrisson, Luciano B Beheregaray, Christopher M Bice, Emily J Booth, Chris J Brauer, Gavin L Butler, David Dawson, Olga Dudchenko, Benjamin G Fanson, Graeme Hackett, Annique Harris, Matthew J Jones, Parwinder Kaur, Wayne M Koster, Kyne Krusic-Golub, Erez Lieberman Aiden, Jason A Lieschke, Jarod Lyon, John R Morrongiello, Nicholas P Murphy, James O'Dwyer, Scott M C Raymond, Meaghan L Rourke, Arron Strawbridge, Jason D Thiem, Zeb Tonkin, Jian D L Yen, Brenton P Zampatti

Staff and Researcher Publications

Freshwater ecosystems and their biota are under increasing pressure from anthropogenic stressors. In response to declining fish stocks, hatchery and stocking programmes are widely implemented as core components of restoration and management strategies, with positive outcomes for some wild populations. Despite this, stocking remains contentious due to potential genetic and ecological risks to wild populations. Monitoring and evaluation of stocking outcomes are critical to ensuring the long-term sustainability of wild populations, but identification of stocked individuals post-release remains a key challenge, particularly for mobile species. In this study, we combined otolith (natal origin and age) and genomic data to identify …

Comparison Between Antigen And Aalelic Hla Mismatches, And The Risk Of Acute Rejection In Kidney Transplant Recipients, Ryan Gately, Anne Taverniti, Narelle Watson, Armando Teixeira-Pinto, Esther Ooi, Rowena Lalji, Ross Francis, Lucy Sullivan, William Mulley, Kate Wyburn, Scott Campbell, Carmel Hawley, Germaine Wong, Wai H. Lim

Research outputs 2022 to 2026

Deceased donor kidney allocation relies on HLA compatibility at the antigen level, as optimal matching reduces the risk of acute rejection. Whether HLA allele-level mismatches improve, the prediction of acute rejection after transplantation remains unclear. Using data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) from 2017 to 2020, HLA antigenic and allelic mismatches between recipients and deceased donors were calculated with imputation of two-field allelic equivalents undertaken where required. The discordance between antigen and allele mismatches was calculated, and oblique random survival forest models were used to predict acute rejection. Predictive performance of antigen (HLA-A, -B, …

Comparison Between Shoulder Flexed And Extended Positions In Elbow Flexion Resistance Training On Regional Hypertrophy And Maximum Strength: Preacher Versus Bayesian Cable Curls, Parsa Attarieh, João Pedro Nunes, Saeed Khani, Saman Negahdar, Amirali Goli, Hamed Nazarirad, Shahriar Nazarirad, Shima Mojtahedi, Kazunori Nosaka, Rahman Soori

Research outputs 2022 to 2026

In the present study, the effects of resistance training on regional hypertrophy and maximum strength of the elbow flexor muscles were compared between elbow flexion exercises performed with different shoulder joint angles (∼50° of flexion vs. extension) while matched for resistance profiles. In a within-subject design, 15 young men (25.6 ± 2.1 y; 77.3 ± 6.8 kg; 175.1 ± 5.7 cm) underwent a resistance training program twice a week for 10 weeks (3–5 sets, 8–12RM), and their arms were dominant-side balanced, randomly assigned to one of the two conditions according to elbow flexion exercises: unilateral cable curl with shoulder flexed …

Resting Energy Expenditure And Metabolic Features In Children With Septo-Optic Dysplasia, David J. Cullingford, Jacqueline A. Curran, Mary B. Abraham, Aris Siafarikas, A. Marie Blackmore, Jenny Downs, Catherine S.Y. Choong

Research outputs 2022 to 2026

Context: Septo-optic dysplasia (SOD) is a major cause of congenital hypopituitarism and is known to be associated with overweight and obesity in up to 44% of children. Given the role of the hypothalamus in hormonal regulation, we sought to assess the association of resting energy expenditure (REE), appetite and physical activity with SOD. Objective: To characterize REE and other metabolic features in patients with SOD and evaluate relationships with elevated body mass index (BMI). Methods: Children with SOD above 5 years of age attending Perth Children's Hospital participated. A CosMED Q-NRG indirect calorimeter was used to calculate mean measure REE …

Impact Of Changes To International Commission On Radiological Protection Models On Occupational Thorium Ore Dust Intake, Gregory S. Hewson, Martin I. Ralph, Marcus Cattani

Research outputs 2022 to 2026

Workers involved in mining and processing naturally occurring radioactive materials (NORMs) are potentially exposed to dust containing alpha particle emitters. The objective of this study is to summarize the key impacts of the latest International Commission on Radiological Protection (ICRP) biokinetic model for thorium ore dust intake and to identify model parameters that require further investigation. The dosimetric significance of thorium ore dust exposure has varied widely over time owing to progressive changes in the inhalation dose coefficients. These changes had a significant influence on radiation protection practices in the Western Australian mineral sand industry, including research initiatives and implementation …

The Relationship Between Visceral Fat Accumulation And Risk Of Cardiometabolic Multimorbidity: The Roles Of Accelerated Biological Aging, Tianyu Zhu, Yixing Tian, Jinqi Wang, Zhiyuan Wu, Wenhan Xie, Haotian Liu, Xia Li, Lixin Tao, Xiuhua Guo

Research outputs 2022 to 2026

Objectives: To investigate the association between visceral fat accumulation and the risk of cardiometabolic multimorbidity (CMM) and the potential roles of accelerated biological aging in this relationship. Methods: Using data from the UK Biobank, a nationwide cohort study was conducted using the available baseline body roundness index (BRI) measurement. Biological aging was assessed using the Klemera–Doubal method for biological age and the phenotypic age algorithms. The association between the BRI and CMM was estimated using the Cox proportional hazards regression model, while the roles of biological aging were examined through interaction and mediation analyses. Results: During a median follow-up of …

Exploring University Student Mental Health And Wellbeing Through A Low-Barrier Peer-Led Service: Emerging Insights From The Living Room, Amanda L. Cole, Fiona Navin, Dawn Reid

Research outputs 2022 to 2026

Universities are increasingly recognising the importance of addressing the social and emotional wellbeing of their students. Mental health challenges experienced while at university can hinder academic achievement and exacerbate existing mental ill-health. In response to this identified need, many institutions have implemented mental health services, such as psychological and counselling support. However, barriers such as stigma, accessibility, and effectiveness often limit their reach and impact. Many students do not avail themselves to services, or access the supports available, due to these barriers. This study gathered initial data from 110 participants who visited Edith Cowan University’s “The Living Room” (TLR) within …

Impact Of A Transplant Nurse Navigator In The Dialysis Setting, Judith D. Pozzerle

Electronic Theses and Dissertations

Patients with kidney disease have better patient outcomes and quality of life with a kidney transplant. However, the transplant process is complicated with inherent inequalities and biases and patients frequently fail to initiate a referral for transplant evaluation. The Centers for Medicare and Medicaid have now placed financial incentives to improve the number of patients transplanted. The only way to increase the number of patients transplanted is to start with a referral for evaluation. Studies have been done highlighting the barriers, but there is a lack of studies implementing strategies to improve these numbers. Utilizing Kotter’s change theory and describing …

Lyset Facilitates Integration Of Both The N- And C-Terminal Transmembrane Helices/Cytoplasmic Domains Of Glcnac-1-Phosphotransferase, Baraj Doray, Benjamin C Jennings, Xi Yang, Lin Liu, Varsha Venkatarangan, Stuart Kornfeld, Ming Li

2020-Current year OA Pubs

LYSET is a recently identified Golgi transmembrane (TM) protein, and inactivating mutations in the

Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional …

Patients' Attitudes To Magnetic Resonance Imaging In Perianal Fistulizing Crohn's Disease: A Global Survey, Easan Anand, Jalpa Devi, Anna Antoniou, Shivani Joshi, Jaap Stoker, Phillip Lung, Ailsa Hart, Phil Tozer, David H Ballard, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: There is limited patient involvement in radiological research for perianal fistulizing Crohn's disease (pfCD), despite magnetic resonance imaging (MRI)'s critical role in diagnosis and management. Patient and public involvement is essential for aligning research with patient priorities. This study aimed to gather patient perspectives on the use of MRI in pfCD.

METHODS: A mixed-methods approach was used, following Guidance for Reporting Involvement of Patients and the Public (GRIPP2) guidelines. An online survey, co-developed with a patient representative, included open and closed questions on MRI experiences, advantages, challenges, and the potential for Artificial Intelligence (AI)-generated reports. This was followed by …

Applying Results Of Extended Genotyping To Management Of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines, L. Stewart Massad, Megan A. Clarke, Rebecca B. Perkins, Francisco Garcia, David Chelmow, Li C. Cheung, Teresa M. Darragh, Didem Egemen, Thomas S. Lorey, Ritu Nayar, Morgan Newman, Carolann Risley, Robert A. Smith, Nicolas Wentzensen, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.

METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through …

Methylomic Signature Of Current Cannabis Use In Two First-Episode Psychosis Cohorts, Emma L Dempster, Emma C Johnson, Et Al.

2020-Current year OA Pubs

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples …

The Internist's Post V.1 N.13, The University Of Texas Rio Grande Valley. School Of Medicine, Jian Garcia Cruz, Julio Javier Perez Rodriguez, Ramon Elizondo Romo, Barbara Malaga-Espinoza, Carlos Alejos Aguero, Osiris Fernandez, Edgar Dorsey Trevino, Diana Othon Martinez, Roque Mifuji Lira, Martha Solis, Cesar Gutierrez

School of Medicine Publications

No abstract provided.

Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay

School of Medicine Publications

Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease’s impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying …

Unraveling Early Onset Disparities And Determinants: An Analysis Of Colorectal Cancer Outcomes And Trends In Texas, Tyler Torres, Elias Arellano Villanueva, Yossef Alsabawi, Demba Fofana, Manish Tripathi

School of Medicine Publications

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the U.S., with disparities in incidence, survival, and age at diagnosis across racial, ethnic, and socioeconomic groups. The rising incidence of early-onset CRC (< 50 years) has amplified concerns regarding access to care, screening disparities, and outcomes, particularly among minorities. This study examines the impact of race, ethnicity, socioeconomic status (SES), and sex on CRC survival and age at diagnosis in Texas from 1995 to 2016.

Methods: This retrospective cohort study utilized Texas Cancer Registry (TCR) data, including 235,076 CRC cases diagnosed between 1995 and 2016. Kaplan-Meier analysis and log-rank tests assessed 10-year survival by race and ethnicity and time period (1995-2005 vs. 2006-2016). Kruskal-Wallis tests with Bonferroni correction were used to compare survival years between racial/ethnic groups within each period. Age at diagnosis was analyzed by race and …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

Acute Kidney Injury In Severe Alcohol-Associated Hepatitis Treated With Anakinra Plus Zinc Or Prednisone, Douglas A Simonetto, Amon Asgharpour, Muhammad Y Jan, Qing Tang, Yunpeng Yu, Yang Li, Moyinoluwa Taiwo, Prashanth Thevkar Nagesh, Srinivasan Dasarathy, Patrick S Kamath, Craig J Mcclain, Naga Chalasani, Gyongyi Szabo, Ramon Bataller, Mack Mitchell, Wajahat Z Mehal, Laura E Nagy, Vijay H Shah, Samer Gawrieh, Arun J Sanyal

Faculty, Staff and Students Publications

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, …

Playbook Workflow Builder: Interactive Construction Of Bioinformatics Workflows, Giacomo B Marino, Anna I Byrd, Mano R Maurya, Sumana Srinivasan, Keyang Yu, Varduhi Petrosyan, Matthew E Roth, Miroslav Milinkov, Charles Hadley King, Jeet Kiran Vora, Jonathon Keeney, Christopher Nemarich, William Khan, Alexander Lachmann, Nasheath Ahmed, Alexandra Agris, Juncheng Pan, Srinivasan Ramachandran, Eoin Fahy, Emmanuel Esquivel, Aleksandar Mihajlovic, Bosko Jevtic, Vuk Milinovic, Sean Kim, Patrick Mcneely, Tianyi Wang, Eric Wenger, Miguel A Brown, Alexander Sickler, Yuankun Zhu, Sherry L Jenkins, Philip D Blood, Deanne M Taylor, Adam C Resnick, Raja Mazumder, Aleksandar Milosavljevic, Shankar Subramaniam, Avi Ma'ayan

Faculty, Staff and Students Publications

The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large …

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

Soluble Mesothelin-Related Peptide As A Prognosticator In Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy, Sung Wook Kang, Jong Min Choi, Ji Seon Shim, Claire Lee, Priyanka Ranchod, Peter Jindra, Maheshwari Ramineni, Meera Patel, R Taylor Ripley, Shawn S Groth, Shanda H Blackmon, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Students Publications

Background: Immune checkpoint therapy (ICT) has significantly impacted the treatment of malignant pleural mesothelioma (MPM). Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.

Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of mesothelin and PD-L1. Both univariable and …