CD33-CD123 IF-THEN gating reduces toxicity while enhancing the specificity and memory phenotype of AML-targeting CAR-T cells.

CAR T-cell therapy has remarkably succeeded in treating lymphoblastic leukemia. However, its success in AML remains elusive due to the risk of on-target off-tumor toxicity to hematopoietic stem and progenitor cells (HSPC) and insufficient T-cell persistence and longevity. Using a SynNotch circuit, we generated a high-precision "IF-THEN" gated logical circuit against the combination of CD33 and CD123 AML antigens and demonstrated anti-tumor efficacy against AML cell lines and patient-derived xenografts.

Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis.

Interleukin (IL)-33 is a key responder to intestinal injury and inflammation. In the colon, it is expressed by several cell populations, with the specific cellular source likely determining its role. The colonic epithelium expresses IL-33; however, the factors controlling its production and the specific epithelial lineage(s) expressing IL-33 are poorly understood.

AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation.

During postnatal life, leptin specifies neuronal inputs to the paraventricular nucleus of the hypothalamus (PVH) and activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. Activity-dependent developmental mechanisms impact refinement of sensory circuits, but whether leptin-mediated postnatal neuronal activity specifies hypothalamic neural projections is largely unexplored. Here, we used chemogenetics to manipulate the activity of AgRP neurons during a discrete postnatal critical period and evaluated the development of AgRP inputs to the PVH and descending efferent outflow to the dorsal vagal complex (DVC).

Association of Discrimination Experiences with Rapid Subsequent Changes in Anxiety and Depressive Symptoms in U.S. Adults During the COVID-19 Pandemic.

This study explores how discrimination experiences during the COVID-19 pandemic relate to anxiety and depressive symptoms in U.S. adults.

Phenotypic Biomarkers of Aqueous Extracellular Vesicles from Retinoblastoma Eyes.

Recent advancements in aqueous humor (AH) cell-free DNA (cfDNA) genomics have opened new avenues for ex vivo molecular profiling of retinoblastoma (RB), the most common pediatric intraocular malignancy, where biopsy is typically prohibited. While these insights offer a genetic blueprint of the tumor, they lack multi-omic molecular phenotyping, which is essential for understanding the functional state. Extracellular vesicles (EVs), naturally present in AH, are promising by offering time-resolved phenotypic information.

Randomized Controlled Feasibility Trial of Late 8-Hour Time-Restricted Eating for Adolescents With Type 2 Diabetes.

Background: No trial to date has tested the effects of late time-restricted eating (lTRE) on glycemic control or body composition in adolescents with type 2 diabetes (T2D).

Objective: The objective of the current study was to examine the feasibility, acceptability, and preliminary efficacy of lTRE compared to a prolonged eating window in adolescents with T2D.

Design: A 12-week, randomized, controlled, feasibility study of lTRE compared to control in adolescents with obesity and new onset T2D was conducted.

Ambient air pollution exposure is associated with liver fat and stiffness in Latino youth with a more pronounced effect in those with PNPLA3 genotype and more advanced liver disease.

Background: Exposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD).

Objectives: We sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity.

Expansion of Medicaid Coverage of Continuous Glucose Monitor Reduces Health Disparity in Children and Young Adults With Type 1 Diabetes.

Background: Continuous glucose monitor (CGM) usage improves glycemia in people with type 1 diabetes (PWD) and is accepted as the standard of care. The CGM utilization is lower in patients with public insurance and minorized ethnicities. In 2022, California Medicaid reduced its barriers to obtaining CGM coverage for PWD.

Flow Characterization in a Partially Liquefied Vitreous Humor.

The purpose of this study is to systematically examine the basic fluid dynamics associated with a fully liquid region within a porous material. This work has come about as a result of our investigation on the ocular fluid dynamics and transport process in a partially liquefied vitreous humor. The liquid is modeled as a sphere with Stokes flow while the surrounding infinite porous region is described by Brinkman flow.

Incidence of an Identifiable Organism in Children Who Underwent a Surgical Procedure for Granulomatous Cervical Lymphadenopathy.

The incidence of cervical lymphadenopathy due to nontuberculous mycobacteria is rising in the pediatric population. Our goal with this study was to review the number of pediatric patients with granulomatous cervical adenitis and determine the incidence of identification of a specific organism as both healthcare providers and parents are interested in identifying the causative pathogen. A retrospective chart review was conducted of patients at a high-volume tertiary care children's hospital between 2017 and 2023.

The overexpression of R-spondin 3 affects hair morphogenesis and hair development along with the formation and maturation of the hair follicle stem cells.

Mice hair follicles (HFs) are a valuable model for studying various aspects of hair biology, including morphogenesis, development, and regeneration due to their easily observable phenotype and genetic manipulability. The initiation and progression of hair follicle morphogenesis, as well as the hair follicle cycle, are regulated by various signaling pathways, of which the main role is played by the Wingless-type MMTV integration site family (Wnt) and the Bone Morphogenic Protein (BMP). During the hair follicle cycle, the BMP pathway maintains hair follicle stem cells (HFSCs) in a dormant state while the Wnt pathway activates them for hair growth.

Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.

The primary objective of omics in space with focus on the human organism is to characterize and quantify biological factors that alter structure, morphology, function, and dynamics of human cells exposed to microgravity. This review discusses exciting data regarding genomics, transcriptomics, epigenomics, metabolomics, and proteomics of human cells and individuals in space, as well as cells cultured under simulated microgravity. The NASA Twins Study significantly heightened interest in applying omics technologies and bioinformatics in space and terrestrial environments.

Bone Accrual Trajectories in Children and Adolescents with Perinatal HIV Infection.

Context: Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort.

Objective: To compare bone accrual in PHIV and healthy children.

Remote data collection of infant activity and sleep patterns via wearable sensors in the HEALthy Brain and Child Development Study (HBCD).

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Wearable and remote sensing technologies have advanced data collection outside of laboratory settings to enable exploring, in more detail, the associations of early experiences with brain development and social and health outcomes. In the HBCD Study, the Novel Technology/Wearable Sensors Working Group (WG-NTW) identified two primary data types to be collected: infant activity (by measuring leg movements) and sleep (by measuring heart rate and leg movements).

Mouse Brain Extractor: Brain segmentation of mouse MRI using global positional encoding and SwinUNETR.

In spite of the great progress that has been made towards automating brain extraction in human magnetic resonance imaging (MRI), challenges remain in the automation of this task for mouse models of brain disorders. Researchers often resort to editing brain segmentation results manually when automated methods fail to produce accurate delineations. However, manual corrections can be labor-intensive and introduce interrater variability.