Medicine and Health Sciences Commons^™

Beyond Shelter: Exploring The Potential Impacts Of Rental Assistance On Self-Reliance And Well-Being For Venezuelan Migrants In Colombia, Lindsay Stark, Juan Pablo Franco, Arturo Harker Roa, Neema Mosha, Deanna Barch, Ned Meerdink, Ilana Seff

2020-Current year OA Pubs

Urban refugees in low- and middle-income countries (LMICs) often face housing insecurity, undermining their ability to achieve self-reliance and well-being. Few studies have evaluated the impact of housing interventions in these contexts. This study offers preliminary evidence on the effectiveness of a 9-month rental assistance program targeting female-headed Venezuelan migrant households in Colombia. Using pre-post data from 517 participants, we assessed changes over time in household-level self-reliance, domains of self-reliance, subjective well-being and perceived agency. We also employed ordinary least squares regression and fixed-effects models to estimate changes in self-reliance and the relationship between self-reliance, psychosocial and housing outcomes. Our …

Specific Effects Of Pulsed Field Ablation On The Cardiac Tissue, The Nervous System And The Conduction System In Experimental And Clinical Studies, Josselin Duchateau, Iwanari Kawamura, Gurukripa N Kowlgi, Elad Maor, Moritz Nies, Christian W Zemlin, Tomás García-Sánchez, Samuel J Asirvatham

2020-Current year OA Pubs

AIMS: Pulsed field ablation (PFA) has emerged as a novel ablation modality for the treatment of cardiac arrhythmias and has rapidly reshaped contemporary electrophysiology practice. This article provides a comprehensive analysis on the mechanisms underlying the specific effects of PFA on myocardial, neural tissue structures, and the cardiac conduction system, integrating biophysical principles with preclinical and clinical evidence relevant to contemporary electrophysiology practice.

METHODS AND RESULTS: This document provides an exhaustive mechanistic explanation for the preferential effects of PFA on myocardium and the limits of the 'tissue-selectivity' concept. The complex interplay between cellular and tissue-level biophysics, biological responses, and tissue …

Birth Cohort Effects In Adults Associated With Influenza A(H1n1)Pdm09 Vaccine Effectiveness, Feng Liu, Stacey L House, Tamair Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: In 2023-2024 influenza season, adults in the 1957-1985 birth cohort had the lowest vaccine effectiveness (VE) against A(H1N1)pdm09 viruses than other age groups, including those in the 1986-2005 birth cohort. We investigated A(H1N1)pdm09 antibody levels in sera collected from influenza cases and controls to explain the birth cohort effect of the low VE.

METHODS: Acute and convalescent sera were collected from adults (1986-2005 and 1957-1985 birth cohorts) during 2023-2024. Hemagglutination inhibiting (HI) and binding antibodies were assessed against representative A(H1N1) viruses and hemagglutinin antigens.

RESULTS: A(H1N1)pdm09-infected cases in the 1957-1985 birth cohort had significantly lower HI antibodies in the …

Real-World Experience Of Hepatitis C Treatment With Glecaprevir-Pibrentasvir During Pregnancy, L Madeline Mccrary, Megan R Curtis, Jeannie C Kelly, Jessica Elrod-Gallegos, Patrick Kojima, Patricia Werner, Jennifer L Mullersman, Tracey Habrock-Bach, Michael J Durkin, Laura R Marks

2020-Current year OA Pubs

Guidelines endorse antenatal hepatitis C virus treatment following shared decision making. No clinical trial or real-world data exist for glecaprevir-pibrentasvir (GLE/PIB). We report our experience with prenatal GLE/PIB in 14 patients. Ten patients completed treatment; all achieved virologic response by or at delivery, with no maternal or neonatal safety concerns.

Study Of Blood Linear Rna Nominates Cd55 And Dld As Early-Stage Biomarkers For Parkinson's Disease, Aleksandra Beric, Sarp Sahin, Santiago Sanchez, Zining Yang, Ravindra Kumar, Isabel Alfradique-Dunham, Jessie Sanford, Daniel Western, Bridget Phillips, John P Budde, Richard J Perrin, Paul T Kotzbauer, Joel S Perlmutter, Scott A Norris, Carlos Cruchaga, Laura Ibanez

2020-Current year OA Pubs

Parkinson's disease (PD) is the second leading neurodegenerative disease, pathologically characterized by the accumulation of alpha-synuclein in the brain and the loss of dopaminergic neurons in the substantia nigra pars compacta. Despite the intensive efforts to identify diagnostic biomarkers for PD and nominating prospective candidates such as such as CSF α-synuclein seed amplification assay or α-/β-synuclein ratio, establishment of minimally invasive biomarkers remains the focus of PD research. We leveraged transcriptomic data from 4343 participants from four independent datasets to robustly identify PD-associated transcripts. Following the differential abundance analyses, we integrated our findings with several brain transcriptomic, CSF proteomic, plasma …

Activity-Dependent Astrocytic Cholesterol Release Fine-Tunes Modes Of Synaptic Exo- And Endocytosis, Jongyun Myeong, Vitaly A Klyachko

2020-Current year OA Pubs

Cholesterol is essential for the organization of neurotransmitter release machinery, yet how it regulates the balance among different forms of synaptic exo- and endocytosis remains poorly understood. Moreover, which pre-synaptic processes rely on neuronal vs. astrocyte-derived cholesterol is unknown. Using nanoscale-precision imaging of single-vesicle release in hippocampal synapses, we demonstrate that astrocytic cholesterol is a critical determinant of both temporal and spatial aspects of presynaptic dynamics by differentially modulating the two main forms of synchronous release, univesicular (UVR) and multivesicular (MVR), effectively fine-tuning their balance. Moreover, astrocytic cholesterol determines the spatial distribution of vesicle release across the active zone and …

A Framework For Aligning 5-Year And Lifetime Breast Cancer Risk In Women Without High-Penetrance Mutations, Graham A Colditz, Debbie L Bennett, Kala Visvanathan, Bernie A Rosner, Shu Jiang

2020-Current year OA Pubs

OBJECTIVE: Reconciling cutoff thresholds for short-term (5-year) and long-term (lifetime) breast cancer risk could support tailored and evidence-based approaches to supplemental screening and risk management most relevant to short-term clinical actions. This study aims to consistently classify women at increased risk and provide 5-year risk cutoff that corresponds to a 20% lifetime risk.

METHODS: Using U.S. Surveillance, Epidemiology and End Results (SEER) program population incidence data for women 40 to 74 years of age, this study reports both lifetime and 5-year population-based risk estimates controlling for competing risk and age varying breast cancer incidence. A cut point for 5-year risk …

Support For Human And Civil Rights In Physical Disability, Mental Illness, And Substance Use Disorder, Jessica Williams, Mia Kouveliotes, Nev Jones, Morgan C Shields

2020-Current year OA Pubs

IMPORTANCE: While there is much research on stigma toward marginalized populations, public perceptions regarding deservingness of basic human and civil rights of these groups have not been examined in a nationwide sample of US adults.

OBJECTIVE: To understand the US public's perceptions regarding deservingness of basic human and contested civil rights for people with severe physical disabilities (SPDs), severe mental illness (SMI), and substance use disorders (SUDs).

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was a nationwide US internet-based quota panel survey of US adults (aged ≥18 years) who completed the survey. Responses were collected from January 17 to February …

Sortscore: Sort-Seq Mave Scoring And Visualization Using Python, Caitlyn Chitwood, Emily Orr, Dustin Baldridge

2020-Current year OA Pubs

SUMMARY: A growing number of tools enable the analysis of large variant libraries produced by multiplexed assays of variant effects (MAVEs). Experiments using fluorescent reporters and fluorescence-activated cell sorting sequencing (FACS-seq or Sort-seq) can coarsely quantify a given variant's impact on phenotypes such as transcription activity. Existing bioinformatics tools for Sort-seq data broadly fall into two categories: methods that model a genotype-phenotype landscape to infer latent variant phenotypes, and methods that directly estimate individual variant scores from experimental binned counts. Within this second category, sortscore provides an activity score computed directly from observed counts without fitting a model, retaining the …

Metanet: A Supervised Ensemble Learning Framework For Reconstructing Direct And Functional Tissue-Specific Transcription Factor Networks, Wooseok J Jung, Sandeep Acharya, Daniel P Ruskin, Shu Liao, Vaha Akbary Moghaddam, Zolboo Erdenebaatar, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: Reconstructing tissue-specific transcription factor (TF) networks remains challenging. TF-motif-based methods often lack functional validation, while expression-based methods struggle to distinguish direct binding from indirect regulation. Integration of diverse data types is necessary to accurately prioritize likely functional targets directly bound by TFs across human tissues.

RESULTS: We introduce METANet (Motif Expression TF Association Networks), a supervised ensemble learning framework that combines TF motifs, cis-regulatory element activity, and linear and nonlinear expression-derived features to predict TF binding. Applied to 36 human tissues, predicted METANet maps significantly outperform established methods in identifying direct, likely functional targets of TFs validated by ChIP-seq …

A Systematic Review And Network Meta-Analysis Of Empirical Antibiotics For Complicated Urinary Tract Infections, Lior Cohen-Yatziv, Emily Gilbert, Ruiwen Zhou, Maria Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Empiric antibiotic selection for complicated urinary tract infections (cUTIs) is increasingly complex due to the rising prevalence of multidrug-resistant organisms. We conducted a network meta-analysis (NMA) to compare clinical efficacy and safety among existing empiric treatment options.

METHODS: We performed a frequentist random-effects NMA of randomized controlled trials evaluating single-agent empiric regimens for adults with cUTIs. The primary endpoints were clinical response (CR), microbiological response, and serious adverse events (AEs). Ceftriaxone served as the common comparator.

RESULTS: Forty-seven trials were identified through a systematic search. In the primary analysis of 17 studies published after the year 2000, evaluating agents …

High-Grade Astrocytoma With Piloid Features: A Clinical And Genomic Analysis Of Prognostic Factors Using A Large Cohort, Shuodan Zhang, Omar H Butt, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well understood. Prognostic factors of clinical outcomes are not well established.

METHODS: Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods.

RESULTS: The cohort comprised 421 patients. There were high rates of ATRX alteration …

Unveiling Functional-Metabolic Synergy In The Healthy Brain: Multivariate Integration Of Dynamic [18f]Fdg-Pet And Resting-State Fmri, Claudia Tarricone, Giulia Vallini, Giorgia Baron, Massimiliano Facca, Erica Silvestri, Tommaso Volpi, Andrei G Vlassenko, Manu S Goyal, Alessandra Bertoldo

2020-Current year OA Pubs

Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [

Emergency Medicine Updates: The Physiologically Difficult Airway, Aaron J Lacy, Brit Long, Michael Gottlieb, Jarrod M Mosier

2020-Current year OA Pubs

INTRODUCTION: Airway management is an integral skill for emergency clinicians. While most of the focus is often on anatomic challenges, clinicians must also consider the unique physiologic challenges that risk decompensation during airway management, often termed the physiologically difficult airway.

OBJECTIVE: This paper evaluates key evidence-based updates concerning management of the physiologically difficult airway for the emergency clinician.

DISCUSSION: Peri-intubation complications in the emergency department are often driven by physiologic instability rather than anatomic difficulty. Key phenotypes of the physiologically difficult airway include hypotension, hypoxemia, metabolic acidemia, and right ventricular dysfunction, and are associated with high rates of physiologic collapse …

Cannabis Retailers' Marketing Practices And Compliance With State Regulations: A 2025 Point-Of-Sale Audit In 5 U.S. Cities, Carla J Berg, Cassidy R Loparco, Matthew E Rossheim, Morgan B Speer, Elizabeth Platt, Caitlin Davie, Hermela Amdeta, Darby Mihelich, Diane M Ndisebuye, Yuxian Cui, Patricia A Cavazos-Rehg, Y Tony Yang, Scott Burris

2020-Current year OA Pubs

Cannabis retail surveillance is crucial to inform regulations and enforcement efforts. This point-of-sale audit study examined marketing practices and compliance with age verification rules, required signage, and marketing restrictions among 161 cannabis retailers in 5 US cities in states authorizing nonmedical cannabis retail (Los Angeles [LA], California; Las Vegas [LV], Nevada; Denver, Colorado; Portland, Oregon; Seattle, Washington) in summer 2025. Descriptive and bivariate analyses characterized retailers overall and across cities. Overall, 84.5 % of retailers requested age verification upon entry (range: Seattle = 43.3 % to LV = 100 %); 8.1 % never verified (range: LV/Denver = 0 % to …

Spatial Bias In Quality Of Estimated Delivery Date Records In The Electronic Health Record, Abigail Lewis, Randi Foraker, Min Lian, Min Zhao, Inez Oh, Aditi Gupta, Antonina Frolova, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVES: This study evaluates the quality of estimated delivery dates (EDD) captured in electronic health record (EHR) systems, focusing on identifying and quantifying bias in these estimates for patients seeking prenatal care.

MATERIALS AND METHODS: We measured spatial and racial biases in the completeness and concordance of EDDs recorded in the EHR for patients seeking prenatal care. Element presence and agreement were compared across the catchment area to identify spatial patterns of bias in EDD records.

RESULTS: We obtained 38 477 unique pregnancy episodes in the EHR representing 33 081 unique patients between 2018 and 2022. Clear spatial and racial …

Characterizing Oseltamivir Use Among Community-Dwelling Patients Diagnosed With Influenza Virus Infection, 2023-2025, Emily A Mcnair, Stephanie A Fritz, Rachel M Presti, Stacey House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Oseltamivir is an antiviral medication for influenza that can reduce the duration of symptoms and may lower the risk of some complications. Recommendations for use of oseltamivir include in the outpatient setting for individuals at higher risk of developing influenza complications. The objectives of the current study were to describe oseltamivir initiation and treatment completion among influenza-positive outpatients and identify factors associated with each.

METHODS: In a US outpatient household transmission study, index participants with laboratory-confirmed influenza provided up to 12 days of detailed information on medication use. We described oseltamivir initiation among index case patients and treatment course …

Lightweight Open-Source Reasoning Large Language Model For Evidence Synthesis Screening, David M Dávila-García, Amanda Gilbert, Adam B Wilcox

2020-Current year OA Pubs

OBJECTIVES: To evaluate performance and efficiency of a lightweight open-source reasoning large language model (LLM) against an expert-derived reference standard for screening scientific publication databases.

MATERIALS AND METHODS: Two expert reviewers screened subsets of database records across 3 stages: (1) base eligibility (

RESULTS: Interreader agreement was near-perfect (

DISCUSSION: The LLM achieved high performance and efficiency relative to an expert-derived reference standard for screening.

CONCLUSION: The use of lightweight open-source reasoning LLMs shows promise to support screening in evidence synthesis workflows.

Using Electronic Health Record Audit Logs To Identify Pediatric Intensive Care Unit Teams, Liem M Nguyen, Stefanie S Sebok-Syer, Dane Jacobson, Karley Mariano, John Grunyk, Shelby Burk, Yasaman Nourkhalaj, Kimberley Kirk, Jochen Profit, Christian Rose, A Jay Holmgren, Thomas Kannampallil, Daniel Tawfik

2020-Current year OA Pubs

BACKGROUND: Teamwork influences patient outcomes, but electronic health records (EHRs) do not reliably capture patient care team members, limiting its study. EHR audit logs provide insights into healthcare workers' workflows and may help identify patients' care team members.

OBJECTIVE: To develop, validate, and compare algorithms utilizing EHR audit logs to identify patient-centric primary teams (bedside nurse, frontline clinician, and attending physician) in pediatric intensive care units (ICUs).

METHODS: We observed rounds for 1931 patient days (development = 678; validation = 1253) across pediatric (PICU), neonatal (NICU) and cardiovascular (CVICU) ICUs at a quaternary children's hospital and documented each patient's daytime …

Functional Role Of Skull Lymphoid Structures In Cns Immunosurveillance, Jang Hyun Park, Daviti Abramishvili, Gustavo Gastão Davanzo, Ruben Silva, Xingxing Gu, Siling Du, Daniel D Lee, Bernd H Zinselmeyer, Jackson S Turner, Gwendalyn J Randolph, Igor Smirnov, Jonathan Kipnis

2020-Current year OA Pubs

Accumulating evidence demonstrates that the central nervous system (CNS) is not disconnected from the peripheral immune system; however, precisely how the adaptive immune system surveils the CNS remains a critical question. Recent findings reveal that channels between the skull and the dura mater facilitate the exchange of cerebrospinal fluid and immune cells between the CNS and skull bone marrow of mice under both homeostatic and disease conditions

Evaluating Large-Scale Propensity Score Adjustment When Sample Size Is Small, Fleur Vereijken, Jenna M Reps, Marc A Suchard, Linying Zhang, George Hripcsak, Peter R Rijnbeek, Ross D Williams, Martijn J Schuemie

2020-Current year OA Pubs

BACKGROUND: Large-scale propensity score (LSPS) models are increasingly used to control confounding in observational studies, but their reliability in small-sample settings is unclear. Small samples can limit a study's ability to estimate propensity scores accurately and achieve adequate covariate balance, raising concerns about insufficient confounding adjustment. Resulting in small datasets being excluded, despite potentially containing valid information.

METHODS: We evaluated the balancing and bias reduction performance of LSPS models using six target-comparator pairs. To emulate a distributed data network analysis setting, we partitioned two large real-world data sources into smaller subsets. Within each subset, LSPS models were fit locally and …

A Deep-Learning Based Biomarker Of Systemic Cellular Senescence Burden To Predict Mortality And Health Outcomes, Shangshu Zhao, Chia-Ling Kuo, Eric J Lenze, Julie L Wetherell, Laura Haynes, Perla El-Ahmad, Richard Fortinsky, George Kuchel, Trevor Harris, Breno S Diniz

2020-Current year OA Pubs

The accumulation of senescent cells is a recognized hallmark of biological aging and is associated with the onset of multiple chronic medical conditions. Senescent cells exhibit a distinct secretory profile, known as the senescence-associated secretory phenotype (SASP), which can propagate cellular senescence to neighboring and distant tissues. Measuring SASP factors in blood serves as a practical proxy for cellular senescence burden and may help track disease states and intervention outcomes. We developed and validated a composite SASP Score by integrating large-scale population proteomics data with a semi-supervised deep learning framework. The analytical workflow included: (1) selection of biologically curated SASP …

Expanded Umbilical Cord Blood Transplantation In Cerebral X-Linked Adrenoleukodystrophy: A Case Report, Rachel E Granberg, Thomas Pfeiffer, Sanil Sansar, Rafael Galindo, Shalini Shenoy

2020-Current year OA Pubs

Umbilical cord blood transplantation is a viable source of stem cells due to accessibility and low incidence of chronic graft-versus-host disease despite human-leukocyte-antigen mismatching. Disadvantages of low stem cell dose in larger recipients include delayed immune reconstitution, graft rejection, and mortality. Successful transplants with ex-vivo expanded cords resulted in approval in malignant disorders and aplastic anemia. We report the first successful expanded cord transplantation in an adolescent with cerebral adrenoleukodystrophy who had no alternative donor/treatment options and required transplant emergently for neurologic preservation. This report highlights a mechanism for timely transplant in metabolic disorders, and preservation of functional advantages despite …

Spatiotemporal Characterization Of Alzheimer Disease Pathology In Living Human Brain Tissue, Aram Aslanyan, Soumya Mukherjee, Yingxin He, Reid Coyle, Chihiro Sato, Nupur Ghoshal, Nicolas R Barthélemy, Srinivas Koutarapu, Katherine Schwetye, Kaleigh F Roberts, Randall J Bateman, Ross W Paterson, Et Al.

2020-Current year OA Pubs

Alzheimer disease begins in the brain many years before symptoms, but early changes are usually studied after death or indirectly through fluid and imaging biomarkers. Here we show that small brain biopsies collected during ventriculoperitoneal shunt surgery can be used to study Alzheimer disease pathology and protein turnover during life. We analysed biopsies from 18 individuals with suspected normal pressure hydrocephalus, alongside matched ventricular and lumbar cerebrospinal fluid and post-mortem control brain tissue. Amyloid plaques were present in 9 of 18 biopsies, while mature tau tangles were rare. Matrix-assisted laser desorption/ionization mass spectrometry imaging mapped amyloid plaque chemistry within tissue. …

Comprehensive Evaluation Of At(N) Imaging Biomarkers For Predicting Cognitive Decline, Tom Earnest, Braden Yang, Deydeep Kothapalli, Aristeidis Sotiras, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

INTRODUCTION: Few studies have investigated how different Alzheimer's disease biomarker definitions affect predictions of cognitive decline.

METHODS: We predicted cognitive decline using 42 biomarker definitions spanning amyloid beta, tau, and neurodegeneration in 383 ADNI participants with baseline neuroimaging and longitudinal cognitive assessments. We identified optimal predictors for each pathology and variable type (continuous, binary, non-binary categorical) using nested cross-validation. Models were compared against support vector machines (SVMs) incorporating brain-wide pathology. In a subsample, we compared imaging-based biomarkers with biofluids (cerebrospinal fluid and plasma).

RESULTS: We observed substantial variability in accuracy, even for measures of the same pathology. Tau biomarkers were …

Cytomegalovirus Immune Responses And Cognitive Impairment In People With Human Immunodeficiency Virus, Lakshmi Chauhan, Debashis Ghosh, Beau Ances, Katherine Tassiopoulos, Kunling Wu, Adriana Weinberg, Kristine M Erlandson

2020-Current year OA Pubs

People with human immunodeficiency virus (HIV) have an earlier occurrence of aging complications, including cognitive impairment (CI). Chronic immune activation from cytomegalovirus (CMV) may contribute to increased inflammation and CI. We explored this association using several measures of CMV immune response among people with HIV (PWH). In a case-control design, we compared CMV immunoglobulin G (IgG), enzyme-linked immunospot (ELISpot), and flow cytometry between cases (subsequent CI) and controls (no CI). Baseline CMV IgG, CMV ELISpot, or flow measures were not associated with subsequent CI. This exploratory analysis supports larger studies using more nuanced immunophenotyping to clarify relationship between CMV and …

Predictive Modeling Of Clonal Hematopoiesis Across Diverse Cohorts, Armel L Batchi-Bouyou, Duc Tran, Michael Raddatz, Teng Gao, Caitlyn Vlasschaert, Brian Sharber, Jie Liu, Giulia Petrone, Irenaeus C C Chan, J Scott Beeler, Griffen Mustion, Alexander G Bick, Sean M Devlin, Kelly L Bolton

2020-Current year OA Pubs

No abstract provided.

Spatial Control Of Parathyroid Hormone Receptor-1 Signaling Dictates Ligand-Specific Biological Outcomes, Jakob Höppner, Harald Jüppner, Monica Reyes, Prem Swaroop Yadav, Dian Wang, Thomas Dean, Patrick Hanna, Roberto Civitelli, Asuka Inoue, Ernestina Schipani, Ignacio Portales-Castillo, Thomas J Gardella

2020-Current year OA Pubs

Parathyroid hormone receptor-1 (PTH1R) is a class B GPCR that regulates mineral ion homeostasis via parathyroid hormone (PTH) and skeletal development via parathyroid hormone-related peptide (PTHrP). While PTHrP signaling is thought to occur predominantly at the plasma membrane, PTH is considered to also signal from endosomes; however, the mechanisms that encode subcellular PTH1R actions, as well as the biological relevance of plasma membrane vs internalized PTH1R activation, remain unclear. Here, by examining the Eiken syndrome mutant R485X-PTH1R, in which C-tail truncation removes key βarrestin docking sites, we identified βarrestins as critical modulators of compartmentalized PTH1R signaling in response to endogenous …

Proteomic Profiling Identifies Systemic Drivers Of Blood-Brain Barrier Injury In Sickle Cell Disease, Yan Wang, Serguei Astafiev, Jinsheng Yu, Slim Fellah, Martin N Reis, Vivian Chen, Amy E Mirro, Chunwei Ying, Kristin P Guilliams, Melanie E Fields, Allison A King, Yasheng Chen, Robert A Campbell, Jorge Di Paola, Carlos Cruchaga, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Sickle cell disease (SCD) causes brain injury and cognitive disability. Systemic inflammation and endothelial injury are central to SCD pathophysiology, yet the relationship between systemic drivers of blood-brain barrier (BBB) disruption and brain injury remains understudied. This cross-sectional study assessed whole-brain and regional BBB permeability (Ktrans) using dynamic contrast-enhanced magnetic resonance imaging for 37 adults with SCD in steady state and 37 adults without SCD. Cerebral oxygen extraction fraction (OEF) and white matter mean diffusivity (MD) measured tissue hypoxia and microstructural injury, respectively. The SCD cohort showed elevated Ktrans compared with controls (3.6 × 10-4·min-1 vs 2.58 × 10-4·min-1; 95% …

The C3-C3ar Axis Modulates Trained Immunity In Alveolar Macrophages, Alexander P Earhart, Rafael Aponte Alburquerque, Marick Starick, Lorena Garnica, Ayse Naz Ozanturk, Rahul Kumar Maurya, Xiaobo Wu, Jeffrey Haspel, Hrishikesh S Kulkarni, Et Al.

2020-Current year OA Pubs

Complement protein C3 is crucial for immune responses in mucosal sites such as the lung, where it aids in microbe elimination, and enhances inflammation. While trained immunity - enhanced secondary responses of innate immune cells after prior exposure - is well-studied, the role of the complement system in trained immune responses remains unclear. We investigated the role of C3 in trained immunity and found that alveolar macrophage (AM)