T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope.

Accumulating evidence supports a critical role for posttranslationally modified (PTM) islet neoantigens in type 1 diabetes. However, our understanding regarding thymic development and peripheral activation of PTM autoantigen-reactive T cells is still limited. Using HLA-DR4 humanized mice, we observed that deamidation of GAD65115-127 generates a more immunogenic epitope that recruits T cells with promiscuous recognition of both the deamidated and native epitopes and reduced frequency of regulatory T cells.

Health Equity: What the Neuroradiologist Needs to Know.

Health equity means that everyone has the opportunity to be as healthy as possible, but achieving health equity requires the removal of obstacles to health such as poverty, discrimination, unsafe environments, and lack of access to health care. The pandemic has highlighted the awareness and urgency of delivering patient-centered, high-value care. Disparities in care are antithetical to health equity and have been seen throughout medicine and radiology, including neuroradiology.

DOT1L activity in leukemia cells requires interaction with ubiquitylated H2B that promotes productive nucleosome binding.

DOT1L methylates histone H3 lysine 79 during transcriptional elongation and is stimulated by ubiquitylation of histone H2B lysine 120 (H2BK120ub) in a classical trans-histone crosstalk pathway. Aberrant genomic localization of DOT1L is implicated in mixed lineage leukemia (MLL)-rearranged leukemias, an aggressive subset of leukemias that lacks effective targeted treatments. Despite recent atomic structures of DOT1L in complex with H2BK120ub nucleosomes, fundamental questions remain as to how DOT1L-ubiquitin and DOT1L-nucleosome acidic patch interactions observed in these structures contribute to nucleosome binding and methylation by DOT1L.

Interferon-β acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation.

Type I interferons (IFNs) are pleiotropic cytokines with potent antiviral properties that also promote protective T cell and humoral immunity. Paradoxically, type I IFNs, including the widely expressed IFNβ, also have immunosuppressive properties, including promoting persistent viral infections and treating T-cell-driven, remitting-relapsing multiple sclerosis. Although associative evidence suggests that IFNβ mediates these immunosuppressive effects by impacting regulatory T (Treg) cells, mechanistic links remain elusive.

Effect of Exposure to Visual Campaigns and Narrative Vignettes on Addiction Stigma Among Health Care Professionals: A Randomized Clinical Trial.

Importance: Stigma toward people with opioid use disorder (OUD) is pervasive in clinical settings, impeding delivery of high-quality care. To date, no study has evaluated the effect of different stigma-reduction messages or messengers among health care professionals.

Objective: To evaluate the effect of OUD-related messages delivered by different messengers on stigma and attitudes toward people with OUD among health care professionals.

Trends in Psychological Distress Among US Adults During Different Phases of the COVID-19 Pandemic.

This survey study assesses trends in psychological distress among US adults surveyed during 4 different phases of the COVID-19 pandemic in 2020 and 2021.

Association Between Symptom Burden at Initiation of a Graduated Return to Activity Protocol and Time to Return to Unrestricted Activity After Concussion in Service Academy Cadets.

Background: Current consensus and position statements recommend that concussed patients be asymptomatic upon the initiation of the graduated return to activity (RTA) protocol. However, a significant number of concussed patients are beginning their RTA protocols while endorsing symptoms.

Purpose: To characterize symptom endorsement at the beginning of the RTA protocol and examine the association between symptom endorsement and RTA protocol duration in service academy cadets.

Applying Care Coordination Principles to Reduce Cardiovascular Disease Risk Factors in People With Serious Mental Illness: A Case Study Approach.

People with serious mental illness (SMI) have a 2-3-fold higher mortality than the general population, much of which is driven by largely preventable cardiovascular disease. One contributory factor is the disconnect between the behavioral and physical health care systems. New care models have sought to integrate physical health care into primary mental health care settings.

How Does Fluid Flow Influence Drug Release from Drug Filled Implants?

Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant itself and avoid the need to include additional drug carrier materials such as a polymers, which are often associated with inflammation and delayed healing/tissue regeneration at the implant site. One common feature of in vitro experiments to generate drug release profiles is stirring or agitation of the release medium.

Drug diffusion and release from a bioerodible spherical capsule.

Controlled release of a drug contained in a spherical polymer capsule is of significant interest in many fields of medicine. There is growing interest in tailoring the erosion properties of the drug to help control and optimize the drug release process. Theoretical understanding of the nature of drug release from a bioerodible capsule is, therefore, important for designing effective drug delivery systems.

Investigation of Aerobic and Muscular Fitness and Concussion Among Service Academy Cadets at the United States Air Force Academy: Results from the CARE Consortium.

Introduction: Concussion has become the signature injury facing the U.S. military.

Studying how state health services delivery policies can mitigate the effects of disasters on drug addiction treatment and overdose: Protocol for a mixed-methods study.

Background: The United States is experiencing a drug addiction and overdose crisis, made worse by the COVID-19 pandemic. Relative to other types of health services, addiction treatment and overdose prevention services are particularly vulnerable to disaster-related disruptions for multiple reasons including fragmentation from the general medical system and stigma, which may lead decisionmakers and providers to de-prioritize these services during disasters. In response to the COVID-19 pandemic, U.

Addressing noise in co-expression network construction.

Gene co-expression networks (GCNs) provide multiple benefits to molecular research including hypothesis generation and biomarker discovery. Transcriptome profiles serve as input for GCN construction and are derived from increasingly larger studies with samples across multiple experimental conditions, treatments, time points, genotypes, etc. Such experiments with larger numbers of variables confound discovery of true network edges, exclude edges and inhibit discovery of context (or condition) specific network edges.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC.

Public support for U.S. social safety net policies throughout the COVID-19 pandemic.

COVID-19 has stretched the U.S. social safety net and prompted federal legislation designed to ameliorate the pandemic's health and economic impacts.

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

Background: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking.

Methods: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy.

Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways.

The transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal.

Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women.

Introduction: Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses.

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries.

Background/objectives: Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry.

Sex and age differences in ICD-11 PTSD and complex PTSD: An analysis of four general population samples.

Background: Posttraumatic stress disorder (PTSD) is traditionally understood as a disorder that occurs more commonly in women than in men, and in younger age groups than in older age groups. The objective of this study was to determine if these patterns are also observed in relation to International Classification of Diseases (ICD-11) PTSD and complex PTSD (CPTSD).

Methods: Secondary data analysis was performed using data collected from three nationally representative samples from the Republic of Ireland (N = 1,020), the United States (N = 1,839), and Israel (N = 1,003), and one community sample from the United Kingdom (N = 1,051).

Association Between Housing Insecurity, Psychological Distress, and Self-rated Health Among US Adults During the COVID-19 Pandemic.

This survey study examines association of housing insecurity with psychological distress and self-rated health among US adults during the COVID-19 pandemic.

Mixed methods protocol to examine the acceptability and clinical characteristics of a remote monitoring programme for delivery of COVID-19 care, among healthcare staff and patients.

Introduction: The use of remote monitoring technology to manage the care of patients with COVID-19 has been implemented to help reduce the burden placed on healthcare systems during the pandemic and protect the well-being of both staff and patients. Remote monitoring allows patients to record their signs and symptoms remotely (eg, while self-isolating at home) rather than requiring hospitalisation. Healthcare staff can, therefore, continually monitor their symptoms and be notified when the patient is showing signs of clinical deterioration.

Radiology Dictation Errors with COVID-19 Protective Equipment: Does Wearing a Surgical Mask Increase the Dictation Error Rate?

Our aim was to determine the effect of wearing a surgical mask on the number and type of dictation errors in unedited radiology reports. IRB review was waived for this prospective matched-pairs study in which no patient data was used. Model radiology reports (n = 40) simulated those typical for an academic medical center.