Digital Commons Network^™

Simultaneous Initiation Of Finerenone And Empagliflozin Across The Spectrum Of Kidney Risk In The Confidence Trial, Muthiah Vaduganathan, Jennifer B Green, Hiddo J L Heerspink, Sung Gyun Kim, Johannes F E Mann, Janet B Mcgill, Amy Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Li Li, Na Li, Katja Rohwedder, Charlie Scott, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a UACR Endpoint) trial investigated the safety and efficacy of simultaneously initiating finerenone and empagliflozin for patients with chronic kidney disease (CKD) and type 2 diabetes. This prespecified analysis aimed to determine if the predicted risk of kidney disease progression, based on KDIGO risk categories, influenced the benefits and safety of this combination therapy.

METHODS: The double-blind, double-dummy trial randomized 818 adults with CKD and type 2 diabetes [urine albumin-creatinine ratio (UACR) ≥100 to < 5000 mg/g] to receive once-daily finerenone plus empagliflozin, finerenone alone or empagliflozin alone, all in addition to a renin-angiotensin system inhibitor. The relative change in UACR from baseline to day 180 (primary endpoint) and a >30% reduction in UACR (secondary endpoint) across KDIGO …

Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin

The Brown Foundation: Institute of Molecular Medicine

Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.

Results: A total of 3158 subjects in 1043 …

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …

Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators

2020-Current year OA Pubs

BACKGROUND: Single-pill combination (SPC) therapy improves hypertension control; however, its implementation in primary care settings remains limited. In Nigeria, there is insufficient evidence on factors influencing SPC uptake, particularly from the perspective of healthcare workers (HCWs). This study examined the implementation of SPC medications for hypertension treatment by nonphysician HCWs at primary healthcare facilities (PHCs) in Nigeria.

METHODS: An explanatory sequential mixed methods study was conducted, building on a cluster randomized controlled trial embedded within the Hypertension Treatment in Nigeria Program. The trial compared SPC medications with free-equivalent combination therapies across 60 PHCs (January-June 2021). A subsequent qualitative component (September-December …

Updating The Epidemiology Of Blastomycosis And Histoplasmosis In The United States, Using National Electronic Health Record Data, 2013-2023., Juliana G E Bartels, Simon K. Camponuri, Theo T. Snow, Brittany L Morgan Bustamante, Natalie J. Kane, Rose Reynolds, Aidan Lee, Mark A. Hoffman, Theodore C. White, Justin V. Remais, Jennifer R. Head

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Where surveillance data are limited, nationally representative electronic health records allow for geographic, temporal, and demographic characterization of the fungal diseases blastomycosis and histoplasmosis.

METHODS: We identified incident blastomycosis and histoplasmosis cases from 2013 to 2023 within Oracle EHR Real-World Data, which comprises 1.6 billion healthcare encounters nationally. To characterize spatiotemporal incidence trends, we used generalized estimating equations weighted for nonrepresentativeness of electronic health record-reporting facilities. We computed standardized incidence rate ratios (sIRRs), which relay relative differences in standardized incidence rates between regions, race/ethnicity, gender, and age subgroups and the national population.

RESULTS: National incidence rates in 2023 were …

The Common Cold Is Associated With Protection From Sars-Cov-2 Infections, Camille M Moore, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 …

Single-Nucleus Multiomics Reveals The Disrupted Regulatory Programs In Three Brain Regions Of Sporadic Early-Onset Alzheimer’S Disease, Andi Liu, Citu Citu, Nitesh Enduru, Xian Chen, Chia-Hao Tung, Tirthankar Sinha, Sofia E Sepulveda, Astrid M Manuel, Damian Gorski, Brisa S Fernandes, Meifang Yu, Paul E Schulz, Lukas M Simon, Claudio Soto, Zhongming Zhao

Faculty, Staff and Student Publications

Sporadic early-onset Alzheimer’s disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type–specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized eight conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Genomic Characterization Of Colorectal Tumors: Insights Into Significantly Mutated Genes, Pathways, And Survival Outcomes, Tabitha A Harrison, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

METHODS: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and …

Pooled Randomised Quartet Trials Assessing Effectiveness Of A Single Pill For Hypertension, Simone Marschner, Mark D Huffman, Desi Quintans, Jody Ciolino, Abigail Baldridge, Danielle Lazar, Emily R Atkins, Graham S Hillis, Mark R Nelson, Markus Schlaich, Anthony Rodgers, Clara K Chow

2020-Current year OA Pubs

BACKGROUND: Hypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.

METHODS: In a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill …

Urinothorax And Empyema: Presentation Of An Unusual Complication Of A Rare Condition, Nolan Fox, Nicholas Fox, Shourjo Chakravorty, Neeraj Sinha

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

A 68-year-old male with a history of metastatic bladder cancer and urinary obstruction presented with intractable hiccups and chest pain is presented in this case. He was found to have a unilateral pleural effusion in addition to ipsilateral renal metastasis abutting the diaphragm. Imaging revealed empyema. Thoracentesis revealed positive cultures and a lack of malignant cells on cytology. Comorbid urinary obstruction and urinary tract infection suggested the rare diagnosis of an infected urinothorax. Thoracentesis also revealed pleural fluid creatinine greater than serum creatinine, meeting the most specific diagnostic criteria for urinothorax and establishing the diagnosis. Treatment aimed at evacuating the …

Clinical Outcomes Of Patients With Unsuccessful Mechanical Thrombectomy Versus Best Medical Management Of Medium Vessel Occlusion Stroke In The Middle Cerebral Artery Territory, Tobias D Faizy, Vivek Yedavalli, Hamza Adel Salim, Dhairya A Lakhani, Basel Musmar, Nimer Adeeb, Muhammed Amir Essibayi, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kuhn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Leonard Ll Yeo, Benjamin Yq Tan, Robert W Regenhardt, Jeremy Josef Heit, Nicole M Cancelliere, Aymeric Rouchaud, Jens Fiehler, Sunil A Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Gaultier Marnat, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea Maria Alexandre, Illario Tancredi, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adam A Dmytriw, Adrien Guenego, Mad-Mt Investigators

Faculty, Staff and Student Publications

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0-2a. Propensity score matching …

Investigating The Polygenic Relationship Between Heavy Cannabis Use And Schizophrenia In The All Of Us Research Program, Isabelle Austin-Zimmerman, Hayley H A Thorpe, John J Meredith, Jibran Y Khokhar, Tian Ge, Marta Di Forti, Arpana Agrawal, Emma C Johnson, Sandra Sanchez-Roige

2020-Current year OA Pubs

BACKGROUND: Decades of research have identified a strong association between heavy cannabis use and schizophrenia (SCZ), with evidence of correlated genetic factors. However, many studies on the genetic relationship between cannabis use and psychosis have lacked data on both phenotypes within the same individuals, creating challenges due to unmeasured confounding. We aimed to address this by using multimodal data from the All of Us Research Program, which contains genetic data as well as information on SCZ diagnosis and cannabis use.

METHODS: We tested the association between cannabis use disorder (CUD) and SCZ polygenic scores (PGSs) with SCZ and heavy cannabis …

Adjudicated Cardiovascular Events In Patients With Covid-19: Association With Vaccination Status And Changes Over Time, Behnood Bikdeli, Darsiya Krishnathasan, Antoine Bejjani, Candrika D. Khairani, Nada Hamade, Umberto Campia, Julia Davies, Nicole Porio, Ali Assi, Andre Armero, Anthony Tristani, Marcos D. Ortiz-Rios, Victor Nauffal, Zaid I. Almarzooq, Eric Q. Wei, Bridget Mcgonagle, Mariana Pfeferman, Sina Rashedi, Alyssa Sato, Giovanni Scimeca, Valeria Zuluaga-Sánchez, Mehrdad Zarghami, Aditya Achanta, Sirus Jesudasen, Bruce C. Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya M. Sharma, Samantha M. Rizzo, Ruth B. Morrison, Alec Vishnevsky, Shiavax J. Rao, Sivan Naveh, Abdelghani El Rafei, James Welker, Marc P. Bonaca, Brett J. Carroll, Samuel Z. Goldhaber, Zhou Lan, Gregory Piazza, The Corona-Vte Network Investigators

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Patients with COVID-19 are at risk of thrombotic and cardiovascular complications. Existing risk estimates derive from early COVID-19 experiences. More recent event rates, temporal trends, and the association between vaccination status and cardiovascular outcomes remain unclear.

METHODS: The CORONA-VTE Network (COVID-19 Registry to Assess Frequency, Risk Factors, Management, and Outcomes of Arterial and Venous Thromboembolic Complications) multicenter registry included patients with COVID-19 from March 2020 to February 2024. A composite of venous and arterial thrombotic events and a composite of adjudicated cardiovascular events were assessed at 90 days after COVID-19 diagnosis. Time-to-first-event analyses were stratified by inpatients and outpatients …

Mbnl Loss Of Function In Smooth Muscle As A Model For Myotonic Dystrophy Associated Gastrointestinal Dysmotility, Janel A M Peterson, Jesus A Frias, Andrew N Miller, Krishnakant G Soni, Yi Zhang, Zheng Xia, John W Day, Geoffrey A Preidis, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of …

Baseline Ecg And Cardiovascular Outcomes In People With Hiv: Insights From Reprieve, Aya Awwad, Shashwatee Bagchi, Et Al.

2020-Current year OA Pubs

BACKGROUND: With antiretroviral therapy, people with HIV (PWH) have an increased burden of cardiovascular disease. The REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial demonstrated that pitavastatin reduces major adverse cardiovascular events (MACEs) among PWH at low to moderate traditional atherosclerotic risk. Electrocardiographic abnormalities are common in PWH, but little is known about their association with MACEs. We sought to examine whether baseline electrocardiographic abnormalities are associated with increased MACE risk among a global primary cardiovascular disease prevention cohort of PWH in REPRIEVE.

METHODS: In this observational analysis, entry electrocardiographic abnormalities were adjudicated and classified as major or …

Emotion Regulation Differences Between Gender And Sexuality Groups: A Systematic Review And Meta-Analysis, Jake Camp, Emma Blundell, Patrick Smith, Katharine Rimes

School of Psychology

Gender and sexual minority (GSM) people are at increased risk of mental health difficulties compared to their cisgender-heterosexual peers. This is likely because of exposure to minority stressors. Emotion regulation difficulties have been proposed as an important mechanism for mental health disparities in GSM populations. This systematic review and meta-analysis examined whether GSM groups differ from cisgender and heterosexual groups in global and specific aspects of emotion regulation (e.g., emotion awareness, strategies, impulse control, cognitive appraisal, and emotion suppression), and whether emotion dysregulation mediated the relationship between GSM identity and mental health outcomes. We identified 40 eligible studies, of which …

Holter Monitor Qt Dispersion And Qtc-Dispersion In Pediatric Long Qt Syndrome And Development Of A Diagnostic And Arrhythmia Risk Prediction Model, Hadeel Allam, Na Le Dang, Edita Karasalihovic, Nathan Miller, Lisa Roelle, William B Orr, Dustin Nash, Anthony G Pompa, Jennifer N A Silva

2020-Current year OA Pubs

BACKGROUND: Holter monitors can provide temporal QT analysis, allowing for calculation of QT dispersion and corrected QT dispersion over time. We describe the results of the QT dispersion and corrected QT dispersion over a 24-hour period in pediatric patients with long QT syndrome (LQTS), compared with a normal cohort, and develop 2 new machine learning models for diagnosis and arrhythmia risk prediction in LQTS.

METHODS: A single-center retrospective case-control study was conducted comparing patients with congenital LQTS and normal controls who underwent a clinically indicated Holter between January 2022 and May 2024. After identifying patients with cardiac events, 2 neural …

The Inferred Functional Connectome Underlying Circadian Synchronization In The Mouse Suprachiasmatic Nucleus, K L Nikhil, Bharat Singhal, Daniel Granados-Fuentes, Jr-Shin Li, István Z Kiss, Erik D Herzog

2020-Current year OA Pubs

Circadian rhythms in mammals arise from the spatiotemporal synchronization of ~20,000 neuronal clocks in the suprachiasmatic nucleus (SCN). Although anatomical, molecular, and genetic approaches have revealed diverse SCN cell types, how network-level wiring enables their synchronization remains unclear. To overcome the challenges of inferring functional connectivity from fixed tissue, we developed Mutual Information & Transfer Entropy (MITE), an information-theoretic framework to infer directed cell-cell connections with high fidelity from long-term live-cell imaging. Recording and analyzing 3,290 h of clock gene expression from 8,261 SCN neurons across 17 mice, we uncovered a highly conserved, sparse SCN network organized into two asymmetrically …

Transdiagnostic Links Of Reward Processing In Obsessive-Compulsive Disorder And Depression, Kevin M Wagner, Matti Cervin, Jessica S C Cheng, Jasmine Arriaga, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Renee M Frederick, Jacey L Anderberg, Belinda E Núñez Bracho, Victor R Adorno, Leonardo F Fontenelle, Andrew D Wiese, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Objectives: Transdiagnostic models aim to uncover shared mechanisms across mental disorders. Reward responsiveness (the ability to experience pleasure from rewarding stimuli) is a plausible, yet underexplored, transdiagnostic mechanism linking obsessive-compulsive disorder (OCD) and depression. This study used network analysis to (1) examine how key reward responsiveness domains are interlinked in individuals with OCD and (2) explore how each domain is uniquely associated with OCD and depression.

Methods: A total of 1345 individuals with a history of OCD symptoms (ages 18-88, 71 % women) from Latino communities in the United States (including Puerto Rico) and nine Latin American countries completed validated …

Loss Of Mfap5 And Its Effect On Skin Homeostasis And Wound Healing, Chen Han, Heidi Yuan, Timothy J Koh, Lin Chen, Robert P Mecham, Luisa A Dipietro

2020-Current year OA Pubs

MFAP5, also known as microfibrillar-associated glycoprotein-2 (MAGP2), may influence parameters of skin wound healing related to scar formation. To further elucidate its role in skin wound healing, we assessed skin wound repair in Mfap5

Methylation-Based Signature To Distinguish Indolent And Aggressive Prostate Cancer, Muheng Liao, Jace Webster, Amy Ly, Emily Rozycki, Christopher A Maher

2020-Current year OA Pubs

Prostate cancer management faces significant challenges in distinguishing indolent from aggressive disease, particularly since most patients are intermediate-risk and therefore hinders the ability to recommend standardized treatment recommendations. Moreover, current prognostic tools including Gleason scoring and tumor staging demonstrate limited accuracy for predicting disease progression and tumor recurrence. DNA methylation serves as a stable epigenetic modification that directly regulates gene expression, making it an ideal biomarker for cancer prognosis. Therefore, this study leveraged whole-genome enzymatic methylation sequencing on 120 patients to develop a novel prognostic signature for aggressive prostate cancer progression. We analyzed 20,849 differentially methylated regions (DMRs) and employed …

Superior Transplant Recipient Outcome Prediction And Pathology Assessment Using Rapid Deep Learning Applied To Procurement Kidney Biopsies, Joseph P Gaut, Jon N Marsh, Ling Chen, Fan Zhang, Xiaobing Yu, Parker Wilson, Ta-Chiang Liu, S Joshua Swamidass

2020-Current year OA Pubs

Evaluating the suitability of deceased organ donor kidneys relies on clinical, laboratory, and biopsy data. Pathologist quantitation of glomerulosclerosis is a critical histologic parameter used in the decision to transplant. This is an arduous task with modest reproducibility and inconsistent correlation with graft outcomes. Prior work shows that deep learning methods automate glomerulosclerosis quantitation with performance superior to on-call pathologists. Extending beyond this prior work, in this study we find that deep learning glomerulosclerosis quantitation better correlates with graft outcomes. A customized and updated deep learning model was used to analyze 691 procurement biopsies of transplanted kidneys with an average …

Cardiometabolic And Molecular Adaptations To 6-Month Intermittent Fasting In Middle-Aged Men And Women With Overweight: Secondary Outcomes Of A Randomized Controlled Trial, Ruteja A Barve, Nicola Veronese, Beatrice Bertozzi, Valeria Tosti, Maria Lastra Cagigas, Francesco Spelta, Edda Cava, Laura Piccio, Dayna S Early, Richard D Head, Luigi Fontana

2020-Current year OA Pubs

Intermittent fasting (IF) has gained attention as a potential intervention for cardiometabolic health, though its long-term effects remain unclear. In this randomized clinical trial, we assessed the impact of 6 months of IF on body composition, cardiovascular risk factors, and related molecular pathways in middle-aged (30-65 years) men and women with overweight (BMI 24.8-35 kg/m²). In this trial, 41 participants were randomized to either an intermittent fasting (IF) intervention or to maintain their habitual diet. The primary outcome (circulating CRP concentration) was previously reported; here, we present exploratory analyses focusing on metabolomic and transcriptomic responses. IF led to an 8% …

Assessing The Efficiency Of Methods To Teach Adolescents About Testicular Cancer And Testicular Self-Examination, Ayşe Gül Güven, Laden Jafari̇, Murat Doğuş Günel, Özlem Akbulut

Turkish Journal of Medical Sciences

Background/aim: Due to the increasing incidence of testicular cancer (TC), early testicular self-examination (TSE) in adolescent males is crucial for early detection and treatment. However, it is uncertain which method is best for teaching about TC and TSE in this age group. This study aimed to assess the effectiveness of formal (face to face with model) and informal (video presentation) approaches in male adolescents about TC and TSE.Material and methods: This intervention study was conducted in 2 high schools, and included a study group (n = 142) and a control group (n = 102). In the study group, a video …

Concurrent Tb And Hiv Therapies Control Tb Reactivation During Co-Infection But Not Chronic Immune Activation, Riti Sharan, Yi Zou, Bindu Singh, Vinay Shivanna, Edward J Dick, Shannan Hall-Ursone, Xi Luo, Guanlin Guo, Shabaana A Khader, Xavier Alvarez, Jyothi Rengarajan, Zhao Lai, Smriti Mehra, Hulin Wu, Deepak Kaushal

Faculty, Staff and Student Publications

Most HIV-negative individuals exposed to Mycobacterium tuberculosis (Mtb) control infection as latent TB infection (LTBI), but HIV co-infection greatly increases progression to tuberculosis (TB), the leading cause of death in people living with HIV (PLHIV). Although combination antiretroviral therapy (cART) reduces LTBI reactivation, immune control of Mtb is not fully restored, as shown by persistent TB incidence in PLHIV on cART. In macaques, skewed pulmonary effector memory CD4⁺ T-cell (TEM) responses and new TB lesions persist despite cART. We hypothesize that concurrent anti-TB therapy with cART would improve bacterial control and immune restoration compared to cART alone. Using …

Stakeholder Criteria For Trust In Artificial Intelligence-Based Computer Perception Tools In Health Care: Qualitative Interview Study, Ansh Rai, Meghan E Hurley, John Herrington, Eric A Storch, Casey J Zampella, Julia Parrish-Morris, Anika Sonig, Gabriel Lázaro-Muñoz, Kristin Kostick-Quenet

Faculty, Staff and Students Publications

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust.

Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care.

Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette …

Early Genetic Evolution Of Driver Mutations In Uveal Melanoma, James J Dollar, Kisha D Piggott, Et Al.

2020-Current year OA Pubs

Uveal melanoma (UM) is an aggressive eye cancer that frequently results in metastatic death despite successful primary tumor treatment. Subclinical micrometastasis is thought to occur early, when tumors are small and difficult to distinguish from benign nevi. However, the early genetic evolution of UM is poorly understood, and biomarkers for malignant transformation are lacking. Here, we perform integrated genetic profiling of 1140 primary UMs, including 131 small tumors. A clinically available 15-gene expression profile (15-GEP) prospectively validated by our group is more accurate than driver mutations for predicting patient survival. Small tumors are significantly more likely to be in earlier …

A Qualitative Exploration Of Patient And Clinician Needs And Preferences For A Physical Activity Intervention During Breast Cancer Chemotherapy, D Carolina Andrade, Loni Parrish, Courtney Harriss, Lindsay L Peterson, Ryan P Duncan, Jingqin Luo, Maura M Kepper, Christine Marx, Mary C Politi, Elizabeth A Salerno

2020-Current year OA Pubs

BACKGROUND: Early intervention with physical activity (PA) during active cancer treatment is critical for improved health outcomes, but often difficult to deliver. We assessed patients' and clinicians' needs and preferences for a PA intervention during chemotherapy via semi-structured interviews.

METHODS: We conducted virtual semi-structured interviews from May 2022 to May 2023 with patients with stage I-III breast cancer and oncology clinicians recruited from a Midwestern comprehensive cancer center and community settings. We identified themes using deductive and inductive thematic analysis informed by the Consolidated Framework for Implementation Research.

RESULTS: Patients (n = 16) were mostly White, non-Hispanic (93.8%) females (100%) …