Antigen experience history directs distinct functional states of CD8 CAR T cells during the antileukemia response.

Although chimeric antigen receptor (CAR) T cells are effective against B-lineage malignancies, post-CAR relapse is common, and efficacy in other tumors is limited. These challenges may be addressed through rational manipulations to control CAR T cell function. Here we examine the impact of cognate T cell antigen experience on subsequent CD8 CAR T cell activity.

Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice.

Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation and persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery.

Next Steps in Efforts to Address the Obesity Epidemic.

Obesity prevalence continues to rise globally at alarming rates, with adverse health and economic implications. In this state-of-the-art review, we provide an analysis of selected evidence about the current knowledge in the obesity literature, including a synthesis of current challenges in obesity and its determinants. In addition, we review past and current efforts to combat the obesity epidemic, highlighting both successful efforts and areas for further development.

Comparison of WatchPAT to polysomnography measurement of apnea-hypopnea index and obstructive sleep apnea severity in adolescents with overweight and obesity.

Study Objectives: The prevalence of obstructive sleep apnea (OSA) increases dramatically in adolescents with overweight or obesity. The gold standard for diagnosis of OSA is in-laboratory polysomnography (PSG). However, access to PSG can be challenging, necessitating development of alternative devices.

Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy.

During pregnancy, marked changes in vasculature occur. The placenta is developed, and uteroplacental and fetoplacental circulations are established. These processes may be negatively affected by genetic anomalies, maternal environment (i.

Global perspectives on transplant disparities.

Purpose Of Review: Our goal was to review and summarize the current state of global disease burden from organ failure and the efforts to improve outcomes with organ transplantation. We also reviewed intra- and inter-country disparities in organ failure and organ transplantation along with potential mechanisms to improve access to organ transplantation globally.

Recent Findings: Many disparities and inequities observed globally can be characterized by the country's income category.

Maternal Plasma Choline Levels Are Positively Correlated with Maternal and Placental Phospholipid-DHA Content in Females with Obesity Who Receive DHA Supplementation.

Background: Pregnancies complicated by maternal obesity are characterized by metabolic differences affecting placental nutrient transport and fetal development. Docosahexaenoic acid (DHA) is critical for fetal brain development and is primarily incorporated into phosphatidylcholine (PC). Recent evidence suggests that choline may enhance PC-DHA synthesis; however, data on the impact of maternal plasma choline on placental phospholipid DHA content in females with obesity are limited.

Beyond the Exam Room: Teaching Intervisit Care to Internal Medicine Residents.

Introduction: Intervisit care, asynchronous care provided between patient visits, represents an essential part of patient care. Despite the importance of intervisit care, residency programs have not traditionally taught residents how to effectively manage intervisit care within the formal curriculum. We aimed to improve resident preparedness in providing intervisit care with an intervisit workshop.

Safety and Efficacy of STREAMLINE Canaloplasty with Phacoemulsification in Hispanic Adults with Open-Angle Glaucoma: 12-Month Outcomes.

Purpose: To report the 12-month clinical outcomes in eyes with mild to moderate open-angle glaucoma (OAG) in Hispanic adults undergoing STREAMLINE Surgical System (STREAMLINE) canaloplasty combined with phacoemulsification.

Patients And Methods: This was a prospective, multi-center, interventional clinical trial involving 45 eyes of 45 Hispanic adult patients receiving topical medical therapy for mild to moderate OAG and undergoing phacoemulsification surgery for visually significant cataracts at three sites. All eyes underwent a Screening visit, followed by medication washout and a subsequent Baseline visit to determine eligibility for STREAMLINE canaloplasty.

Social support and self-efficacy during early adolescence: Dual impact of protective and promotive links to mental health and wellbeing.

This study aimed to assess the impact of sources of social support and dimensions of self-efficacy on psychological symptoms and mental wellbeing among early adolescents. A total of 274 adolescents aged 10-14 from Darjeeling, India, participated in the study. The Multidimensional Scale of Perceived Social Support (MSPSS) and Self-Efficacy Questionnaire for Children (SEQ-C) were utilized to assess dimensions of protective/promotive factors.

A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth.

Clade 2.3.4.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Rare variants in cardiomyopathy genes predispose to cardiac injury in severe COVID-19 patients of African or Hispanic ancestry.

In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2.

Acetylation of proximal cysteine-lysine pairs by alcohol metabolism.

Alcohol consumption induces hepatocyte damage through complex processes involving oxidative stress and disrupted metabolism. These factors alter proteomic and epigenetic marks, including alcohol-induced protein acetylation, which is a key post-translational modification (PTM) that regulates hepatic metabolism and is associated with the pathogenesis of alcohol-associated liver disease (ALD). Recent evidence suggests lysine acetylation occurs when a proximal cysteine residue is within ∼15 Å of a lysine residue, referred to as a cysteine-lysine (Cys-Lys) pair.

Feasibility of newborn screening for pyridoxine-dependent epilepsy.

Background: Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy historically characterized by seizures that are resistant to antiseizure medications. Treatment with pyridoxine and lysine reduction therapies are associated with seizure control and improved developmental outcomes. In rare circumstances, patients have died prior to diagnosis and treatment with pyridoxine, and many patients are diagnosed after six months of age when lysine reduction therapies have limited efficacy.

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.

A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

SHAPE: A visual computing pipeline for interactive landmarking of 3D photograms and patient reporting for assessing craniosynostosis.

3D photogrammetry is a cost-effective, non-invasive imaging modality that does not require the use of ionizing radiation or sedation. Therefore, it is specifically valuable in pediatrics and is used to support the diagnosis and longitudinal study of craniofacial developmental pathologies such as craniosynostosis - the premature fusion of one or more cranial sutures resulting in local cranial growth restrictions and cranial malformations. Analysis of 3D photogrammetry requires the identification of craniofacial landmarks to segment the head surface and compute metrics to quantify anomalies.