Medicine and Health Sciences Commons^™

Therapeutic Approaches To Modulate The Immune Microenvironment In Gliomas, Andreas Sarantopoulos, Chibawanye Ene, Elisa Aquilanti

Faculty, Staff and Student Publications

Immunomodulatory therapies, including immune checkpoint inhibitors, have drastically changed outcomes for certain cancer types over the last decade. Gliomas are among the cancers that have seem limited benefit from these agents, with most trials yielding negative results. The unique composition of the glioma immune microenvironment is among the culprits for this lack of efficacy. In recent years, several efforts have been made to improve understanding of the glioma immune microenvironment, aiming to pave the way for novel therapeutic interventions. In this review, we discuss some of the main components of the glioma immune microenvironment, including macrophages, myeloid-derived suppressor cells, neutrophils …

Impact Of Select Actionable Genomic Alterations On Efficacy Of Neoadjuvant Immunotherapy In Resectable Non-Small Cell Lung Cancer, Nicolas Zhou, Cheuk H Leung, William N William, Annikka Weissferdt, Apar Pataer, Myrna C B Godoy, Brett W Carter, Frank V Fossella, Anne S Tsao, George R Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M Kurie, Mehmet Altan, Charles Lu, Bonnie S Glisson, Lauren A Byers, Yasir Y Elamin, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Jack A Roth, Hai T Tran, Jia Wu, Luisa M Solis Soto, Humam Kadara, Stephen G Swisher, Ara A Vaporciyan, Don L Gibbons, Heather Y Lin, J Jack Lee, John V Heymach, Marcelo V Negrao, Boris Sepesi, Tina Cascone

Faculty, Staff and Student Publications

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Methods: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF …

The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …

Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, …

The Growing Divide Between Teaching Empathy And Being Empathetic, Arindam Sarkar

Faculty, Staff and Students Publications

No abstract provided.

Construction And Characterization Of Dna Libraries From Cultured Phages And Environmental Viromes, Carmen Gu Liu, Brianna E Thompson, James D Chang, Lorna Min, Anthony W Maresso

Faculty, Staff and Students Publications

Despite many efforts to understand and leverage the functional potential of environmental viromes, most bacteriophage genes are largely uncharacterized. To explore novel biology from uncultivated microbes like phages, metagenomics has emerged as a powerful tool to directly mine new genes without the need to culture the diverse microbiota and the viruses within. When a pure computational approach cannot infer gene function, it may be necessary to create a DNA library from environmental genomic DNA, followed by the screening of that library for a particular function. However, these screens are often initiated without a metagenomic analysis of the completed DNA library …

The Alzheimer's Disease Neuroimaging Initiative-4 (Adni-4) Engagement Core: A Culturally Informed, Community-Engaged Research (Ci-Cer) Model To Advance Brain Health Equity, Mónica Rivera Mindt, Alyssa Arentoft, Amanda T. Calcetas, Vanessa A. Guzman, Hannatu Amaza, Adeyinka Ajayi, Miriam T. Ashford, Omobolanle Ayo, Lisa L. Barnes, Gladys Maestre

School of Medicine Publications

Introduction: The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimer's disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment.

Methods: URPs include ethnoculturally minoritized, lower education (≤ 12 years), and rural populations. The CI-CER model includes: (1) culturally informed methodology (e.g., less restrictive inclusion/exclusion criteria, sociocultural measures, financial compensation, results disclosure, Spanish Language Capacity Workgroup) and (2) inclusive engagement methods (e.g., the Engagement Core team; Hub Sites; Community-Science Partnership Board).

Results: As …

Demographic Characteristics, Perinatal Smoking Patterns, And Risk For Neonatal Health Complications Among Pregnant Smokers In The United States Who Begin Using Electronic Cigarettes During Pregnancy: A Descriptive Study Using Population-Based Surveillance Data., Hui Nian, Rachel Odland, Samantha Mindlin, Lin Ammar, Hilary Tindle, Angela M Miller, Kelli K Ryckman, Ethan Xie, Tina V Hartert, Brittney M Snyder, Steven M Brunwasser, Pingsheng Wu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy.

AIMS AND METHODS: Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified …

Environmental House Calls Can Reduce Symptoms Of Chemical Intolerance: A Demonstration Of Personalized Exposure Medicine, Rudolfo Rincón, Roger Perales, Raymond F. Palmer, Jackie F. Forster, Jessica F. Hernandez, Bryan Bayles, Carl Grimes, Carlson R. Jaén, Claudia S. Miller

Public Health (Archived)

Aim: The goals of this investigation were to 1) identify and measure exposures inside homes of individuals with chemical intolerance (CI), 2) provide guidance for reducing these exposures, and 3) determine whether our environmental house calls (EHCs) intervention could reduce both symptoms and measured levels of indoor air contaminants.

Background: CI is an international public health and clinical concern, but few resources are available to address patients’ often disabling symptoms. Numerous studies show that levels of indoor air pollutants can be two to five (or more) times higher than outdoor levels. Fragranced consumer products, including cleaning supplies, air fresheners, and …

Impact Of An Individualized Pain Plan To Treat Sickle Cell Disease Vaso-Occlusive Episodes In The Emergency Department, Lauren Siewny, Allison King, Cathy L Melvin, Christopher R Carpenter, Jane S Hankins, Joseph S Colla, Liliana Preiss, Lingzi Luo, Lisa Cox, Marsha Treadwell, Natalia Davila, Rita V Masese, Sarah Mccuskee, S Siera Gollan, Paula Tanabe

2020-Current year OA Pubs

To address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were aged 18 to 45 years, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed …

Gene Therapy For Fat-1 Prevents Obesity-Induced Metabolic Dysfunction, Cellular Senescence, And Osteoarthritis, Ruhang Tang, Natalia S Harasymowicz, Chia-Lung Wu, Yun-Rak Choi, Kristin Lenz, Sara J Oswald, Farshid Guilak

2020-Current year OA Pubs

Obesity is one of the primary risk factors for osteoarthritis (OA), acting through cross talk among altered biomechanics, metabolism, adipokines, and dietary free fatty acid (FA) composition. Obesity and aging have been linked to cellular senescence in various tissues, resulting in increased local and systemic inflammation and immune dysfunction. We hypothesized that obesity and joint injury lead to cellular senescence that is typically associated with increased OA severity or with aging and that the ratio of omega-6 (ω-6) to omega-3 (ω-3) FAs regulates these pathologic effects. Mice were placed on an ω-6-rich high-fat diet or a lean control diet and …

The Representation Of Decision Variables In Orbitofrontal Cortex Is Longitudinally Stable, Manning Zhang, Alessandro Livi, Mary Carter, Heide Schoknecht, Andreas Burkhalter, Timothy E Holy, Camillo Padoa-Schioppa

2020-Current year OA Pubs

The computation and comparison of subjective values underlying economic choices rely on the orbitofrontal cortex (OFC). In this area, distinct groups of neurons encode the value of individual options, the binary choice outcome, and the chosen value. These variables capture both the choice input and the choice output, suggesting that the cell groups found in the OFC constitute the building blocks of a decision circuit. Here, we show that this neural circuit is longitudinally stable. Using two-photon calcium imaging, we record from the OFC of mice engaged in a juice-choice task. Imaging of individual cells continues for up to 40 …

Hepatocyte Period 1 Dictates Oxidative Substrate Selection Independent Of The Core Circadian Clock, Jiameng Sun, Yiming Zhang, Joshua A Adams, Cassandra B Higgins, Shannon C Kelly, Hao Zhang, Kevin Y Cho, Ulysses G Johnson, Benjamin M Swarts, Shun-Ichi Wada, Gary J Patti, Leah P Shriver, Brian N Finck, Erik D Herzog, Brian J Debosch

2020-Current year OA Pubs

Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period 1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate that hepatocyte Per1-deficient mice fail to transit from oxidation of glucose …

Identification Of The N-Terminal Residues Responsible For The Differential Microdomain Localization Of Cyp1a1 And Cyp1a2, Robert M. Fuchs, James R. Reed, J. Patrick Connick, Markéta Paloncýová, Martin Šrejber, Petra Čechová, Michal Otyepka, Marilyn K. Eyer, Wayne L. Backes

School of Graduate Studies Faculty Publications

The endoplasmic reticulum is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at …

Early Use Of Long-Acting Injectable Antipsychotics In Bipolar Disorder Type I: An Expert Consensus, Martha Sajatovic

Faculty Scholarship

Introduction: Long-acting injectable antipsychotics (LAIs) are not routinely offered to patients living with bipolar disorder type I (BP-I), despite widespread evidence that supports their benefits over oral antipsychotics, particularly in early disease. Methods: A round-table meeting of psychiatrists convened to discuss barriers and opportunities and provide consensus recommendations around the early use of LAIs for BP-I. Results: LAIs are rarely prescribed to treat BP-I unless a patient has severe symptoms, sub-optimal adherence to oral antipsychotics, or has experienced multiple relapses. Beyond country-specific accessibility issues (e.g., healthcare infrastructure and availability/approval status), primary barriers to the effective use of LAIs were identified …

Key Data Elements For A Successful Pediatric Rheumatology Virtual Visit: A Survey Within The Pr-Coin Network., Y Ingrid Goh, Meghan E. Ryan, Shoghik Akoghlanian, Rajdeep Pooni, Julia G. Harris, Danielle R. Bullock, Sheetal S. Vora, Tzielan C. Lee, Shirley M L Tse, Fatima Barbar-Smiley

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease which is commonly monitored by a combination of history, physical examination, bloodwork, and imaging. The COVID-19 pandemic prompted a rapid shift to telemedicine to ensure that patients continued to receive healthcare. The shift to telemedicine changed the methodology and ability of healthcare providers to monitor their patients' progress, as they were unable to perform direct hands-on assessments. The following survey sought to understand the impact of switching pediatric rheumatology healthcare delivery from in-person to telemedicine modality. Specifically, it sought to examine the rate of collection of critical data …

Social Inequalities In Child Mental Health Trajectories: A Longitudinal Study Using Birth Cohort Data 12 Countries, Tim Cadman, Demetris Avraam, Jennie Carson, Ahmed Elhakeem, Veit Grote, Kathrin Guerlich, Mònica Guxens, Laura D. Howe, Rae Chi Huang, Jennifer R. Harris, Tanja A.J. Houweling, Eleanor Hyde, Vincent Jaddoe, Pauline W. Jansen, Jordi Julvez, Berthold Koletzko, Ashleigh Lin, Katerina Margetaki, Maria Melchior, Johanna Thorbjornsrud Nader, Marie Pedersen, Costanza Pizzi, Theano Roumeliotaki, Morris Swertz, Muriel Tafflet, David Taylor-Robinson

Research outputs 2022 to 2026

BACKGROUND: Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age. METHODS: We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each …

Optical Genome Mapping For Detection Of Bcr::Abl1-Another Tool In Our Toolbox, Zhenya Tang, Wei Wang, Gokce A Toruner, Shimin Hu, Hong Fang, Jie Xu, M James You, L Jeffrey Medeiros, Joseph D Khoury, Guilin Tang

Faculty, Staff and Student Publications

Background:BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up.

Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1.

Results:BCR:ABL1 was detected by FISH and RT-PCR …

Unmasking Neuroendocrine Prostate Cancer With A Machine Learning-Driven Seven-Gene Stemness Signature That Predicts Progression, Agustina Sabater, Pablo Sanchis, Rocio Seniuk, Gaston Pascual, Nicolas Anselmino, Daniel F Alonso, Federico Cayol, Elba Vazquez, Marcelo Marti, Javier Cotignola, Ayelen Toro, Estefania Labanca, Juan Bizzotto, Geraldine Gueron

Faculty, Staff and Student Publications

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting seven-gene signature (KMT5C, DPP4, TYMS, CDC25B, IRF5, MEN1, and DNMT3B) was validated across independent cohorts and patient-derived xenograft (PDX) models. This signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, …

Nutritional Intervention As Adjuvant Therapy For T-Cell Acute Lymphoblastic Leukemia, Miriam B Garcia, Palaniraja Thandapani

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Pik3ca Gain And Pten Loss On Mantle Cell Lymphoma Biology And Sensitivity To Targeted Therapies, Nardjas Bettazova, Jana Senavova, Kristyna Kupcova, Dana Sovilj, Anezka Rajmonova, Ladislav Andera, Karla Svobodova, Adela Berkova, Zuzana Zemanova, Lenka Daumova, Vaclav Herman, Alexandra Dolníkova, R Eric Davis, Marek Trneny, Pavel Klener, Ondrej Havranek

Faculty, Staff and Student Publications

Besides many other mutations in known cancer driver genes, mantle cell lymphoma (MCL) is characterized by recurrent genetic alterations of important regulators of the phosphoinositol-3-kinase (PI3K) cascade including PIK3CA gains and PTEN losses. To evaluate the biological and functional consequences of these aberrations in MCL, we have introduced transgenic expression of PIK3CA (PIK3CA UP) and performed knockout/knockdown of PTEN gene (PTEN KO/KD) in 5 MCL cell lines. The modified cell lines were tested for associated phenotypes including dependence on upstream B-cell receptor (BCR) signaling (by an additional BCR knockout). PIK3CA overexpression decreased the dependence of the tested MCL on prosurvival …

Cortical Acetylcholine Dynamics Are Predicted By Cholinergic Axon Activity And Behavior State, Erin Neyhart, Na Zhou, Brandon R Munn, Robert G Law, Cameron Smith, Zakir H Mridha, Francisco A Blanco, Guochuan Li, Yulong Li, Ming Hu, Matthew J Mcginley, James M Shine, Jacob Reimer

Faculty, Staff and Students Publications

Acetylcholine (ACh) is thought to play a role in driving the rapid, spontaneous brain-state transitions that occur during wakefulness; however, the spatiotemporal properties of cortical ACh activity during these state changes are still unclear. We perform simultaneous imaging of GRAB-ACh sensors, GCaMP-expressing basal forebrain axons, and behavior to address this question. We observed a high correlation between axon and GRAB-ACh activity around periods of locomotion and pupil dilation. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, and local ACh activity decreased at farther distances from an axon. Deconvolution of GRAB-ACh traces allowed us to account for sensor kinetics …

Native Mass Spectrometry Of Membrane Protein-Lipid Interactions In Different Detergent Environments, Smriti Kumar, Lauren Stover, Lie Wang, Hanieh Bahramimoghaddam, Ming Zhou, David H Russell, Arthur Laganowsky

Faculty, Staff and Students Publications

Native mass spectrometry (MS) reveals the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer. However, detergents commonly used for structural studies, such as dodecylmaltoside, tend to generate highly charged ions, leading to protein unfolding, thereby diminishing their utility in characterizing protein–lipid interactions. Thus, there is a critical need to develop approaches to investigate protein–lipid interactions in different detergents. Here, we demonstrate how charge-reducing molecules, such as spermine and trimethylamine-N-oxide, enable the opportunity to characterize lipid binding to the bacterial water channel (AqpZ) and …

Gene-Specific Effects On Brain Volume And Cognition Of Tmem106b In Frontotemporal Lobar Degeneration, Marijne Vandebergh, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES:

METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic variant in

RESULTS: The minor allele of

DISCUSSION: We identified associations of

Sars-Cov-2 Anti-N Antibodies Among Healthcare Personnel Without Previous Known Covid-19, Sajal Tiwary, Caroline A O'Neil, Kate Peacock, Candice Cass, Mostafa Amor, Meghan A Wallace, David Mcdonald, Olivia Arter, Kelly Alvarado, Lucy Vogt, Henry Stewart, Daniel Park, Victoria J Fraser, Carey-Ann D Burnham, Christopher W Farnsworth, Jennie H Kwon

2020-Current year OA Pubs

OBJECTIVE: To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity.

DESIGN: Prospective cohort study from September 22, 2020, to March 3, 2022.

SETTING: A tertiary care academic medical center.

PARTICIPANTS: 727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up.

METHODS: At enrollment and follow-up 1-6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures.

RESULTS: Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test …

Multiomics Profiling Of Mouse Polycystic Kidney Disease Progression At A Single-Cell Resolution, Yoshiharu Muto, Yasuhiro Yoshimura, Haojia Wu, Monica Chang-Panesso, Nicolas Ledru, Owen M Woodward, Patricia Outeda, Tao Cheng, Moe R Mahjoub, Terry J Watnick, Benjamin D Humphreys

2020-Current year OA Pubs

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes. We catalog differentially expressed genes and activated epigenetic regions in each cell type during PKD progression, characterizing cell-type-specific responses to

The Vldlr Entry Receptor Is Required For The Pathogenesis Of Multiple Encephalitic Alphaviruses, Sathvik Palakurty, Saravanan Raju, Alan Sariol, Zhenlu Chong, Ngan Wagoner, Hongming Ma, Ofer Zimmerman, Lucas J Adams, Camille Carmona, Zhuoming Liu, Daved H Fremont, Sean P J Whelan, William B Klimstra, Michael S Diamond

2020-Current year OA Pubs

The very-low-density lipoprotein receptor (VLDLR) has been reported as an entry receptor for Semliki Forest (SFV) and Eastern equine encephalitis (EEEV) alphaviruses in cell cultures. However, the role of VLDLR in alphavirus pathogenesis and the extent to which other alphaviruses can engage VLDLR remains unclear. Here, using a surface protein-targeted CRISPR-Cas9 screen, we identify VLDLR as a receptor for Western equine encephalitis virus (WEEV) and demonstrate that it promotes the infection of multiple viruses in the WEE antigenic complex. In vivo studies show that the pathogenicity of WEEV, EEEV, and SFV, but not the distantly related Venezuelan equine encephalitis virus, …

Open Access In The Age Of Ai: The Journal Of Appalachian Health And Hurricane Helene Recovery, Noah Wren, Bradley Firchow

Journal of Appalachian Health

The recent destruction brought upon the Appalachian region by Hurricane Helene has emphasized the importance of the Journal of Appalachian Health. As an open-access peer-reviewed source of information, the Journal plays a critical role in not only facilitating public health research about Hurricane Helene, but also combating misinformation regarding the event. In the days following Hurricane Helene, misinformation about the federal government’s response, along AI generated images, have left many in the region confused and misled about what had happened. Going forward, the Journal will play an necessary part in making sure accurate information is shared to understand how …

Open Access Partnerships To Enhance Research Impact, Mark Geil

All Things Open

10 AM | Open Access Publishing Partnership with Frontiers

Mark Geil, Associate Dean of Research and Operation of Wellstar College of Health and Human Services and Professor of Exercise Science

Credentialing Care: Covid-19 And The Bureaucratization Of Doulas, Ellen Block, Julie Johnson Searcy, Angela N. Castañeda

Sociology Faculty Publications

Doulas in the United States offer embodied, informational, and continuous one-on-one care to birthing people. Doulas have historically sought certification to gain knowledge through training and to gain legitimacy for healthcare providers and clients. During the COVID-19 pandemic, hospitals required doulas to provide proof of certification. The COVID-19 pandemic, and the proliferation of state-sponsored doula programs, has sparked a shift in how doulas are viewed and regulated, enabling new forms of bureaucratic oversight and control. Based on participant observation, surveys, and semi-structured interviews, we examine the connection between certification and care including motivations doulas have for certification, the perceived value …