Digital Commons Network^™

Physical Activity Measurement Reactivity Among Midlife Adults With Elevated Risk For Cardiovascular Disease: Protocol For Coordinated Analyses Across Six Studies., Kiri Baga, Gabrielle M Salvatore, Iris Bercovitz, Amanda L Folk, Ria Singh, Laura M König, Meghan L Butryn, Jacqueline A Mogle, Danielle Arigo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United States, and adults aged 40-60 years with specific health conditions are at particularly elevated risk for developing CVD. Physical activity (PA) is a key cardioprotective behavior and many interventions exist to promote PA in this group. Effective promotion requires accurate assessment of PA behavior; as PA is often estimated by averaging across multiple days, a threat to accurate assessment is measurement reactivity, or an atypical increase in PA behavior at the start of measurement periods that may bias conclusions. Evidence for PA measurement reactivity is equivocal, though …

Development And Validation Of A Dynamic Real-Time Risk Prediction Model For Intensive Care Units Patients Based On Longitudinal Irregular Data: Multicenter Retrospective Study, Zhuo Zheng, Jiawei Luo, Yingchao Zhu, Lei Du, Lan Lan, Xiaobo Zhou, Xiaoyan Yang, Shixin Huang

Faculty, Staff and Student Publications

Background: Timely and accurate prediction of short-term mortality is critical in intensive care units (ICUs), where patients' conditions change rapidly. Traditional scoring systems, such as the Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation, rely on static variables collected within the first 24 hours of admission and do not account for continuously evolving clinical states. These systems lack real-time adaptability, interpretability, and generalizability. With the increasing availability of high-frequency electronic medical record (EMR) data, machine learning (ML) approaches have emerged as powerful tools to model complex temporal patterns and support dynamic clinical decision-making. However, existing models are …

Impact Of Antidiabetic Medication Type On A New Episode Of Depression: A Retrospective Cohort Study In Texas, Usa, Lin-Na Chou, Mukaila A Raji, Holly M Holmes, Yong-Fang Kuo

Faculty, Staff and Student Publications

Objectives: To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

Design: A retrospective cohort study.

Setting: A population-based study using the Texas Medicare data.

Interventions: 11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

Participants: This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, …

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis In 24 539 Individuals, Yezhi Pan, Chuan Bi, Zhenyao Ye, Hwiyoung Lee, Jiaao Yu, Luba Yammine, Tianzhou Ma, Peter Kochunov, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Introduction: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored.

Aims and methods: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco …

The Combined Effect Of High-Intensity Interval Training And Time-Restricted Feeding On The Akt-Igf-1-Mtor Signaling Pathway In The Muscle Tissue Of Type 2 Diabetic Rats, Motahareh Mohebinejad, Fatemeh Kazeminasab, Mahtab Ghanbari Rad, Reza Bagheri, Mazdak Razi, Darryn Willoughby, Fred Dutheil

Faculty, Staff and Students Publications

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats.

Methods: 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) …

Disuse-Driven Plasticity In The Human Thalamus And Putamen, Roselyne J Chauvin, Dillan J Newbold, Ashley N Nielsen, Ryland L Miller, Samuel R Krimmel, Athanasia Metoki, Anxu Wang, Andrew N Van, David F Montez, Scott Marek, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Jarod L Roland, Abraham Z Snyder, Benjamin P Kay, Marcus E Raichle, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach

2020-Current year OA Pubs

Subcortical plasticity has mainly been studied using invasive electrophysiology in animals. Here, we leverage precision functional mapping (PFM) to study motor plasticity in the human subcortex during 2 weeks of upper-extremity immobilization with daily resting-state and motor task fMRI. We found previously that, in the cortex, limb disuse drastically impacts disused primary motor cortex functional connectivity (FC) and is associated with spontaneous fMRI pulses. It remains unknown whether disuse-driven plasticity pulses and FC changes are cortex specific or whether they could also affect movement-critical nodes in the thalamus and striatum. Tailored analysis methods now show spontaneous disuse pulses and FC …

Parapneumonic Empyema Complicating Community-Acquired Pneumonia: Etiology In The Era Of Pneumococcal Vaccination And Role Of Molecular Diagnosis, Antonio C Arrieta, Stephanie Osborne, Lindsay R Grant, Bradford D Gessner, Anne J Blaschke, Kristina G Hulten, Delma J Nieves, Ashley Miller, Cody Bender, Raul Isturiz, Ronika Alexander, Shannon M Nielsen, Linda B Lamberth, Alejandro Cane, Adriano Arguedas

Faculty, Staff and Students Publications

Background: Impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease is well described; pneumococcus is infrequently identified by culture in pneumonia. Yield is higher when pleural fluid is cultured. Polymerase chain reaction (PCR) in pleural fluid samples improves pathogen identification, particularly in the case of S. pneumoniae.

Methods: Healthy children with empyema who underwent pleural fluid drainage were eligible. Demographics and PCV immunization status were collected. Blood/pleural fluid cultures were obtained. Pleural fluid samples were sent for PCR for pathogen. Serotyping was done by Neufeld-Quellung reaction on pneumococcus isolates, and PCR in culture negative cases.

Results: From December 2018 to …

Center-Ing Black Voices: Incorporating Lived Experience Across The Research Process To Advance Equity In Drug Treatment And Outcomes, Devin E Banks, Maria E Paschke, Kaytryn D Campbell, Daje D Bradshaw-Glenn, Rashmi Ghonasgi, Burton Barr, Arial Collins, Gerald Dennis, Keith Lofton, Alfred Long, Harriet Montgomery, Andreas Prince, Rachel P Winograd

2020-Current year OA Pubs

BACKGROUND: Black people in the United States face persistent and increasing inequities in addiction treatment access and drug overdose death. Incorporating people with lived experience through community based participatory research (CBPR) approaches can improve understanding of drivers of and solutions to such inequities. However, practical and systemic challenges limit incorporating Black people with lived experience with substance use across each step of the research process. This paper describes the methods, recommendations, and lessons learned from a research team and Black-led community advisory board (CAB) working together across the research process to promote equity in harm reduction and addiction treatment.

METHODS: …

Partnering With Social Media Influencers To Promote Hpv Vaccination In Diverse Communities, Amy Leader, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Preethi Selvan, Kayla Madden, Joshua Banks, Angela Sustaita-Ruiz

Department of Medical Oncology Faculty Papers

BACKGROUND: While human papillomavirus (HPV) vaccination is one of the most effective ways to prevent HPV-related cancers, many children and adolescents remain unvaccinated. Resistance often stems from parental vaccine hesitancy and mistrust of the health care system, both of which may be higher in communities of color. Partnering with social media influencers may be an effective method for disseminating health messages. We tested the impact of HPV social media posts developed by influencers on outcomes of knowledge, attitudes, and intentions to vaccinate.

METHODS: Ten social media influencers who identified as African American or Hispanic created posts about the HPV vaccine. …

Mendelian Randomization Study Of Sleep Traits And Risk Of Colorectal Cancer, Olympia Dimopoulou, Yin Cao, Et Al.

2020-Current year OA Pubs

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using …

Determining Potential Immunomodulatory Drug Efficacy In Sepsis Using Elispot, Andrew H Walton, Dale F Osborne, Ethan B Davitt, Anne M Drewry, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

This study evaluated the ability of ELISpot to identify potential immuno-modulatory drug therapies in sepsis. ELISpot was performed ex vivo on whole blood from septic patients and healthy controls. Innate and adaptive immunity were evaluated by production of TNF-α and IFN-γ, respectively. Drug efficacy was determined by their effects to modulate the both the number of cytokine-producing cells and amount of cytokine produced per cell. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance …

Enhancement Of The Endocannabinoid System Through Monoacylglycerol Lipase Inhibition Relieves Migraine-Associated Pain In Mice, Elizaveta Mangutov, Yaseen Awad-Igbaria, Kendra Siegersma, Francois Gastambide, Ayodeji A Asuni, Amynah A A Pradhan

2020-Current year OA Pubs

BACKGROUND: Migraine affects over 1 billion people worldwide and is a leading cause of disability. Targeting the cannabinoid system offers a promising approach for pain and migraine relief. This study evaluated a novel monoacylglycerol lipase (MAGL) inhibitor to prolong endocannabinoid action in acute and chronic mouse models of migraine. It also examined MAGL and cannabinoid receptor 1 (CB

METHODS: C57BL6/J male and female mice received the human migraine trigger nitroglycerin (NTG) acutely or every other day for 9 days. Allodynia was assessed by von Frey hair stimulation of the periorbital area. A single dose of MAGL inhibitor (ABD-1970) was tested …

A Deep Learning Strategy To Identify Cell Types Across Species From High-Density Extracellular Recordings, Maxime Beau, David J Herzfeld, Francisco Naveros, Marie E Hemelt, Federico D'Agostino, Marlies Oostland, Alvaro Sánchez-López, Young Yoon Chung, Michael Maibach, Stephen Kyranakis, Hannah N Stabb, M Gabriela Martínez Lopera, Agoston Lajko, Marie Zedler, Shogo Ohmae, Nathan J Hall, Beverley A Clark, Dana Cohen, Stephen G Lisberger, Dimitar Kostadinov, Court Hull, Michael Häusser, Javier F Medina

Faculty, Staff and Students Publications

High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but fail to reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals and reveal the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetics and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep learning classifier that predicts cell types with greater than 95% accuracy based on the waveform, discharge …

The Geographic Identification Of Elevated Suicide Risk Model: Evaluating A Method For Examining Suicide-Related Behaviors At The Neighborhood Level In Harris County, Texas, Ryan M Hill, Sam C Cacace, Austin Starkey, Tyler Hendley, Jackson Bolner, Angela Cummings, Angie Hayes, Robert J Cramer

Faculty, Staff and Students Publications

Background: The 2024 National Strategy for Suicide Prevention has called for the development of community-based suicide prevention resources, and improved existing prevention efforts. In line with such efforts, Hill and colleagues developed the Geospatial Identification of Elevated Suicide Risk model that estimates the relative prevalence of adolescent suicide risk within specific geographical areas. The current study seeks to further evaluate and refine the model for use as a tool to evaluate risk and protective factors at the neighborhood level.

Method: Drawing from multiple sources, data was collected detailing adolescent suicidal ideation, suicide attempts, suicide fatalities, and census tract characteristics. Utilizing …

Age-Related Meningeal Extracellular Matrix Remodeling Compromises Cns Lymphatic Function, Kate Hitpass Romero, Taylor J Stevenson, Leon C D Smyth, Ben Watkin, Samuel J C Mccullough, Luca Vinnell, Amy M Smith, Patrick Schweder, Jason A Correia, Jonathan Kipnis, Mike Dragunow, Justin Rustenhoven

2020-Current year OA Pubs

Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a …

Asynchronous Development Of The Mouse Auditory Cortex Is Driven By Hemispheric Identity And Sex, Ashlan P Reid, Demetrios Neophytou, Robert Levy, Cody Pham, Hysell V Oviedo

2020-Current year OA Pubs

Lateralized auditory processing is essential for specialized functions such as speech processing, typically dominated by the Left Auditory Cortex (ACx) in humans. Hemispheric specializations also occur in the adult mouse ACx, but their developmental origins are unclear. Our study finds that the Left and Right ACx in mice reach developmental milestones at different ages. Thalamocortical responses and maturation of synaptic dynamics develop earlier in the Right ACx than the Left. We show that this timing offset predicts hemisphere-dependent differences in sensory-driven plasticity. Juvenile tone exposure at specific times results in imbalanced adult tone frequency representations in the Right and Left …

The Essential Calcium Channel Of Sperm Catsper Is Temperature-Gated, Dilip K Swain, Citlalli Vergara, Júlia Castro-Arnau, Polina V Lishko

2020-Current year OA Pubs

The flagellar calcium channel CatSper is essential for male fertility, as it regulates calcium influx to trigger the hyperactive motility required for sperm to fertilize the egg. Precise activation of CatSper is critical, as premature activation can impair sperm function. While optimal temperature is known to influence fertilization, its effect on CatSper remains unknown. By directly recording from mouse spermatozoa, we reveal that CatSper functions as a temperature-gated ion channel, with a thermal threshold of 33.5 °C and a temperature coefficient Q

Using The Healthy Native Youth Implementation Toolbox To Provide Web-Based Adolescent Health Promotion Decision Support To American Indian And Alaska Native Communities: Implementation Study, Amrita Sidhu, Ross Shegog, Stephanie Craig-Rushing, Nicole Trevino, Michelle Singer, Cornelia Jessen, Gwenda Gorman, Sean Simpson, Melissa Peskin, Belinda Hernandez, Christine Markham

Faculty, Staff and Student Publications

Background: American Indian and Alaska Native (AI/AN) youth experience numerous health inequities, including those in sexual, reproductive, and mental health. Implementation of culturally relevant, age-appropriate evidence-based programs may mitigate these inequities. However, numerous barriers limit the adoption and implementation of evidence-based adolescent health promotion programs in AI/AN communities.

Objective: This study examines user reach and engagement from 2022 to 2024 of web-based decision support (the Healthy Native Youth [HNY] website and the embedded HNY Implementation Toolbox), designed to increase the implementation of evidence-based adolescent health promotion programming in AI/AN communities.

Methods: Promotional strategies were designed for optimal geographic reach to …

Developing An Online Community Advisory Board (Cab) Of Parents From Social Media To Co-Design An Human Papillomavirus Vaccine Intervention: Participatory Research Study, Regan M. Murray, Shawn C. Chiang, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Wen-Juo Lo, Philip M. Massey

Department of Medical Oncology Faculty Papers

BACKGROUND: Social media health interventions have grown significantly in recent years. However, researchers are still developing innovative methods to meaningfully engage online communities to inform research activities. Little has been documented describing this approach of using online community advisory boards (CABs) to co-create health communication interventions on social media.

OBJECTIVE: This study describes the formation, engagement, and maintenance of an online CAB focused on co-creating a health education intervention for parents regarding the human papillomavirus (HPV) vaccine. The study provides guiding principles for public health researchers implementing such CABs in future digital health interventions.

METHODS: In May 2020, Twitter was …

Elevated Mitochondrial Membrane Potential Is A Therapeutic Vulnerability In Dnmt3a-Mutant Clonal Hematopoiesis, Kira A Young, Grant A Challen, Et Al.

2020-Current year OA Pubs

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Mri Distance Measures As A Predictor Of Subsequent Clinical Status During The Preclinical Phase Of Alzheimer's Disease And Related Disorders, Xinyi Zhang, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Brain atrophy over time, as measured by magnetic resonance imaging (MRI), has been shown to predict subsequent cognitive impairment among individuals who were cognitively normal when first evaluated, indicating that subtle brain atrophy associated with Alzheimer's disease (AD) may begin years before clinical symptoms appear. Traditionally, atrophy has been quantified by differences in brain volume or thickness over a specified timeframe. Research indicates that the rate of atrophy varies across different brain regions, which themselves exhibit complex spatial and hierarchical organizations. These characteristics collectively emphasize the need for diverse summary measures that can effectively capture the multidimensional nature of degeneration. …

Cerebrospinal Fluid Proteomics Identification Of Biomarkers For Amyloid And Tau Pet Stages, Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali, Jigyasha Timsina, Menghan Liu, Carlos Cruchaga, Jianping Jia

2020-Current year OA Pubs

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as …

Single-Cell Analyses Reveal A Functionally Heterogeneous Exhausted Cd8+ T-Cell Subpopulation That Is Correlated With Response To Checkpoint Therapy In Melanoma, Kelly M Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M Haugh, Laura A Huppert, Lauren S Levine, Margaret M Lowe, Michael Alvarado, Markee Micu, Katy K Tsai, Melissa Chow, Meromit Singer, Jason M Schenkel, Arlene H Sharpe, Michael D Rosenblum, Kristen E Pauken, Adil I Daud

Faculty, Staff and Student Publications

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the …

Integrated Analysis Of Molecular And Clinical Features Associated With Overall Survival In Melanoma Patients With Brain Metastasis, Swaminathan Kumar, Meredith S Pelster, Merve Hasanov, Renato A Guerrieri, Courtney W Hudgens, Debora A Ledesma, Fuchenchu Wang, Grant M Fischer, Julie M Simon, Lauren E Haydu, Kalman V Katlowitz, Y N Vashisht Gopal, Jennifer L Mcquade, Lawrence N Kwong, Jason T Huse, Alexander J Lazar, Michael T Tetzlaff, Jeffrey E Gershenwald, Aron Y Joon, Ken Chen, Ziyi Li, Prahlad T Ram, Sherise D Ferguson, Michael A Davies

Faculty, Staff and Student Publications

Melanoma brain metastases (MBMs) are diagnosed in up to 60% of metastatic melanoma patients. Previous studies have identified clinical factors that correlate with overall survival (OS) after MBM diagnosis. However, molecular and immune features associated with OS are poorly understood. An improved understanding of the molecular and immune correlates of OS could provide insights into MBM patient outcomes and guide therapeutic development. Thus, we analyzed clinical features and outcomes of 74 melanoma patients who underwent surgical resection (via craniotomy) between 1991 and 2015 at our institution with RNA-seq data generated from their MBMs. The median post-operative OS was 8.6 months …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Left Ventricular Entry To Reduce Brain Lesions During Catheter Ablation: A Randomized Trial, Gregory M Marcus, Roderick Tung, Edward P Gerstenfeld, Trisha F Hue, Feng Lin, Jing Cheng, J Peter Weiss, Wendy S Tzou, Henry Hsia, Ashkan Ehdaie, Daniel H Cooper, T Jared Bunch, Jeffrey Arkles, Babak Nazer, Adam Lee, Alexios Hadjis, Duy T Nguyen, Mihail G Chelu, Joshua Moss, Jonathan C Hsu, Miguel Valderrábano, Prashant D Bhave, Andrew D Beaser, Arvindh Kanagasundram, Oussama Wazni, Jason Bradfield, Grace Wall, Kathleen Chang, Michelle Yang, Gabrielle Montenegro, Sabrina Jarrott, Joel H Kramer, Anthony S Kim, Yvonne M Morris, William P Dillon

Faculty, Staff and Students Publications

Background: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging-detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach.

Methods: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left …

A Screening Question To Assess Risk Of Using Antibiotics Without A Prescription: A Diagnostic Study, Ashley Collazo, Eva Amenta, Kiara Olmeda, Marissa Valentine-King, Lindsey Laytner, Azalia Mancera, Roger Zoorob, Michael K Paasche-Orlow, Richard L Street, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Objectives: Non-prescription antibiotic use (using antibiotics without medical advice) is potentially unsafe and promotes antimicrobial resistance. We studied predictors of prior non-prescription use and whether screening for prior non-prescription antibiotic use predicted intention of future non-prescription antibiotic use.

Methods: The survey was performed from January 2020 - June 2021 in six public primary care clinics and two private emergency departments. Prior non-prescription users were respondents who reported taking oral antibiotics for symptoms without contacting a clinician. Intended use was defined by answering yes to the question, "would you use antibiotics without contacting a doctor/nurse/dentist/clinic." We examined predictors for prior non-prescription …