The T cell receptor sequence influences the likelihood of T cell memory formation.

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease.

Background/objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD.

Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV)/forced vital capacity (FVC) < 0.

Utilization and Outcomes Associated With Intravascular Ultrasound During Abdominal and Thoracic Endovascular Aortic Interventions in the United States in the Contemporary Era (2016-2023).

Background: Intravascular ultrasound (IVUS) use in aortic endovascular interventions, including thoracic endovascular aneurysm repair (TEVAR) and endovascular aneurysm repair (EVAR), may have similar benefits to those seen in coronary and peripheral interventions, but limited utilization and outcome data exist.

Methods: Centers for Medicare and Medicaid Services claims data were used to identify patients undergoing TEVAR and EVAR from 2016 to 2023. Utilization trends were stratified by region, urbanicity, distressed communities index, community versus academic center, Medicare versus dual enrollment status, indication, urgency, and presence of dissection with malperfusion.

Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.

Background: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

Enhancing mental health literacy and care through community-driven solutions in rural Bangladesh.

Women in rural Bangladesh encounter significant barriers to seeking mental healthcare, primarily due to stigmatization rooted in a lack of knowledge about mental health. To address this issue, community-based participatory research (CBPR) has been identified as a promising approach. CBPR involves the active collaboration of community members and stakeholders in the research process to tackle pressing community issues.

Impact of maternal antenatal nutrition and infection treatment interventions on Longitudinal Infant Development and Growth in rural Ethiopia: protocol of the LIDG child follow-up study.

Introduction: Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventions on long-term growth and neurodevelopmental outcomes of offspring.

Why is low educational attainment linked to worse pain and function in fibromyalgia?

Lower educational attainment has been linked to worse pain in individuals with chronic pain, but the mechanisms of this relationship are not fully elucidated. This observational study analyzed the relationship between educational attainment and pain in patients with fibromyalgia (FM) and the potential psychological mechanisms driving this relationship. We hypothesized that (1) lower educational attainment would be associated with greater pain intensity and interference, and that (2) concerns about pain (CAP), anxiety, and depression would mediate the relationship between educational attainment and pain.

Spotlight on YAP: Unlocking New Insights to Overcome the Barriers to Heart Regeneration.

This editorial refers to “Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration” by Liu . and “YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division” by Morikawa

Penalizing underage alcohol use is associated with lower mortality for young drivers: Use/lose laws and their association with motor vehicle collision mortality.

Background: Motor vehicle collisions (MVC) continue to be a leading cause of mortality for youth in the United States. Since 2010, seven states have revoked mandatory laws that suspended licenses for underage alcohol use, also known as use/lose laws. This study analyzed whether each state's policy change was associated with increased youth MVC mortality.

Antifouling Immunomodulatory Copolymer Architectures That Inhibit the Fibrosis of Implants.

Immune reactions to medical implants often lead to encapsulation by fibrotic tissue and impaired device function. This process is thought to initiate by protein adsorption, which enables immune cells to attach and mount an inflammatory response. Previously, several antifibrotic materials have been either designed to reduce protein adsorption or discovered via high-throughput screens (HTS) to favorably regulate inflammation.

Integrating Hydrogels and Biomedical Plastics via In Situ Physical Entanglements and Covalent Bonding.

Both rigid plastics and soft hydrogels find ample applications in engineering and medicine but bear their own disadvantages that limit their broader applications. Bonding these mechanically dissimilar materials may resolve these limitations, preserve their advantages, and offer new opportunities as biointerfaces. Here, a robust adhesion strategy is proposed to integrate highly entangled tough hydrogels and diverse plastics with high interfacial adhesion energy and strength.

Analysis of Informatics Topics in Accreditation Council for Graduate Medical Education Program Requirements.

Background:  There is growing recognition of the need to incorporate informatics education in U.S. residencies.

Oxidative stress promotes lipid-laden macrophage formation via CYP1B1.

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation.

A dual-focus approach for evaluating contributors to chronic pain: The roles of psychosocial risk and resilience factors.

There has been a predominant focus on psychosocial risk factors associated with poor pain outcomes among individuals with chronic pain. However, it is also important to identify resilience factors that may mitigate the negative impact of or confer successful adaptation to pain. We argue for a dual-focus approach that evaluates the contributions of both risk and resilience factors.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Understanding Cognitive Aging Through White Matter: A Fixel-Based Analysis.

Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.

Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana.

Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.

Characterization of focused ultrasound blood-brain barrier disruption effect on inflammation as a function of treatment parameters.

The technology of focused ultrasound-mediated disruption of the blood-brain barrier (FUS-BBB opening) has now been used in over 20 Phase 1 clinical trials to validate the safety and feasibility of BBB opening for drug delivery in patients with brain tumors and neurodegenerative diseases. The primary treatment parameters, FUS intensity and microbubble dose, are chosen to balance sufficient BBB disruption to achieve drug delivery against potential acute vessel damage leading to microhemorrhage. However, other safety considerations due to second order effects caused by BBB disruption, such as inflammation and alteration of neurovascular function, are only beginning to be understood.

Days at Home After Transcatheter Mitral Valve Repair Versus Medical Therapy Alone in Heart Failure.

Background: Transcatheter edge-to-edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient-centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1- and 2-year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.

Myocarditis in Patients Starting Combination Checkpoint Inhibitor Therapy: Analysis of a Commercial Claims Database.

Background: Immune checkpoint inhibitors have improved the clinical outcomes of several cancers but have also been associated with a greater risk of immune-related adverse effects, especially when combined. The objective of this study was to investigate the incidence of myocarditis in relation to the use of dual concurrent versus single immune checkpoint inhibitors therapies.

Methods And Results: A cohort study was conducted using medical and pharmacy claims data (2011-2022) from a large US commercial insurer.

Real-world treatment patterns, healthcare resource utilisation and costs in patients with SLE in the USA.

Objective: To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA.

Methods: Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period.

A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate.

Mycobacterium tuberculosis causes human tuberculosis. As mycobacteria are protected by thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors.