TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids.

Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model systems to identify and examine these factors using clinically relevant biospecimens are limited. In this study, we examined the activity of B7-H3-directed CAR T cells (B7-H3.

Monkey Lateral Prefrontal Cortex Subregions Differentiate between Perceptual Exposure to Visual Stimuli.

Each day, humans must parse visual stimuli with varying amounts of perceptual experience, ranging from incredibly familiar to entirely new. Even when choosing a novel to buy at a bookstore, one sees covers they have repeatedly experienced intermixed with recently released titles. Visual exposure to stimuli has distinct neural correlates in the lateral prefrontal cortex (LPFC) of nonhuman primates.

Iron Deficiency Anemia in Children During and After PICU Stay: Single-Center Retrospective Cohort, 2021-2022.

Objectives: The primary objective was to determine iron deficiency (ID) anemia (IDA) monitoring practices in children during PICU stay. A secondary objective was to determine the current follow-up practices for IDA after PICU discharge.

Design: Retrospective observational study of 2 years (2021-2022).

Variability of interobserver interpretation of selected helminth ova in the development of a training image set.

Background: Diagnosis of soil-transmitted helminthiasis and schistosomiasis for surveillance relies on microscopic detection of ova in Kato-Katz (KK) prepared slides. Artificial intelligence (AI)-based platforms for parasitic eggs may be developed using a robust image set with defined labels by reference microscopists. This study aimed to determine interobserver variability among reference microscopists in identifying parasite ova.

Flux through membrane channel: linear transport single-molecule approaches.

One of the most subtle steps in the single-molecule approach to the flux through the membrane channel, which uses the one-dimensional Smoluchowski equation, is to describe the molecule's "behavior" at the contacts between the channel openings and the bulk. Earlier, to handle this issue, we introduced the so-called "radiation boundary conditions" that account for the interplay between the two types of trajectories of the molecules starting at the openings, specifically, the ones that eventually return to the channel and the ones that escape to infinity. The latter trajectories represent the true translocation events on the condition that initially the molecule entered the channel from the opposite side.

" " Exploring the Experiences of Black and Hispanic Parents following a Congenital Heart Disease Diagnosis.

 Congenital heart disease (CHD) is an important contributor to pediatric morbidity and mortality. Unfortunately, disparities in the diagnosis and treatment of CHD exist across racial and ethnic groups. The objective of this study was to share the experiences of Hispanic and Black families with CHD to better understand their needs.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Sexual dimorphism in lung transcriptomic adaptations in fetal alcohol spectrum disorders.

Current fetal alcohol spectrum disorders (FASD) studies primarily focus on alcohol's actions on the fetal brain although respiratory infections are a leading cause of morbidity/mortality in newborns. The limited studies examining the pulmonary adaptations in FASD demonstrate decreased surfactant protein A and alveolar macrophage phagocytosis, impaired differentiation, and increased risk of Group B streptococcal pneumonia with no study examining sexual dimorphism in adaptations. We hypothesized that developmental alcohol exposure in pregnancy will lead to sexually dimorphic fetal lung morphological and immune adaptations.

Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint.

Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear.

Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

Population-level amplification of gene regulation by programmable gene transfer.

Engineering cells to sense and respond to environmental cues often focuses on maximizing gene regulation at the single-cell level. Inspired by population-level control mechanisms like the immune response, we demonstrate dynamic control and amplification of gene regulation in bacterial populations using programmable plasmid-mediated gene transfer. By regulating plasmid loss rate, transfer rate and fitness effects via Cas9 endonuclease, F conjugation machinery and antibiotic selection, we modulate the fraction of plasmid-carrying cells, serving as an amplification factor for single-cell-level regulation.

Quantitative magnetization transfer and g-ratio imaging of white matter myelin in early psychotic spectrum disorders.

Myelin abnormalities in white matter have been implicated in the pathophysiology of psychotic spectrum disorders (PSD), which are characterized by brain dysconnectivity as a core feature. Among evidence from in vivo MRI studies, diffusion imaging findings have largely supported disrupted white matter integrity in PSD; however, they are not specific to myelin changes. Using a multimodal imaging approach, the current study aimed to further delineate myelin and microstructural changes in the white matter of a young PSD cohort.

Cellular and organismal function of choline metabolism.

Choline is an essential micronutrient critical for cellular and organismal homeostasis. As a core component of phospholipids and sphingolipids, it is indispensable for membrane architecture and function. Additionally, choline is a precursor for acetylcholine, a key neurotransmitter, and betaine, a methyl donor important for epigenetic regulation.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Streptomyces secretes a siderophore that sensitizes competitor bacteria to phage infection.

To overtake competitors, microbes produce and secrete secondary metabolites that kill neighbouring cells and sequester nutrients. This metabolite-mediated competition probably evolved in complex microbial communities in the presence of viral pathogens. We therefore hypothesized that microbes secrete natural products that make competitors sensitive to phage infection.

A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers.

Accurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC.

A lifespan-generalizable skull-stripping model for magnetic resonance images that leverages prior knowledge from brain atlases.

In magnetic resonance imaging of the brain, an imaging-preprocessing step removes the skull and other non-brain tissue from the images. But methods for such a skull-stripping process often struggle with large data heterogeneity across medical sites and with dynamic changes in tissue contrast across lifespans. Here we report a skull-stripping model for magnetic resonance images that generalizes across lifespans by leveraging personalized priors from brain atlases.

Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions.

Large language models for the mental health community: framework for translating code to care.

Large language models (LLMs) offer promising applications in mental health care to address gaps in treatment and research. By leveraging clinical notes and transcripts as data, LLMs could improve diagnostics, monitoring, prevention, and treatment of mental health conditions. However, several challenges persist, including technical costs, literacy gaps, risk of biases, and inequalities in data representation.

Continuous vital sign monitoring of patients recovering from surgery on general wards: a narrative review.

Most postoperative deaths occur on general wards, often linked to complications associated with untreated changes in vital signs. Monitoring in these units is typically intermittent checks each shift or maximally every 4-6 h, which misses prolonged periods of subtle changes in physiology that can herald a critical downstream event. Continuous monitoring of vital signs is therefore intuitively necessary for patient safety.

Chromosome-level echidna genome illuminates evolution of multiple sex chromosome system in monotremes.

Background: A thorough analysis of genome evolution is fundamental for biodiversity understanding. The iconic monotremes (platypus and echidna) feature extraordinary biology. However, they also exhibit rearrangements in several chromosomes, especially in the sex chromosome chain.

A comparative study of Merkel cell carcinoma and melanoma incidence and survival in the United States, 2000-2021.

Merkel cell carcinoma (MCC) and melanoma are important contributors to skin cancer mortality in the United States. We evaluated their epidemiology using US cancer registry data. During 2000-2021, 19,444 MCCs and 646,619 melanomas of the skin were diagnosed.

Effect of extrinsic pigmentation and multiple firing cycles on the properties of a zirconia-containing lithium silicate ceramic.

Purpose: To assess the impact of staining and multiple firings on the mechanical, optical, and surface characteristics of zirconia-containing lithium silicate ceramics (ZLS).

Materials And Methods: Ninety ZLS discs (Suprinity, VITA Zahnfabrick) were divided according to the "Number of firings" protocol: Ctr-control, no characterization; SC-single firing cycle (for characterization, crystallization and staining simultaneously); and DC-double firing cycle (crystallization firing cycle was performed separately from the staining firing). Extrinsic pigmentation was performed to replicate the characterization of a monolithic restoration.