Effective targeting of PDGFRA-altered high-grade glioma with avapritinib.

PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans.

High resolution autoradiography of [F]MK-6240 and [F]Flortaucipir shows similar neurofibrillary tangle binding patterns preferentially recognizing middling neurofibrillary tangle maturity.

Recent developments in tau positron emission tomography (PET) radiotracers have enhanced the visualization of tau aggregates in Alzheimer's disease (AD). The maturity level of neurofibrillary tangles can affect its recognition by biomarkers. Early detection of tau aggregates regarding tangle pathology is of interest in early diagnosis and comparison of tau radiotracers in this aspect is important.

Depressive symptoms among women of reproductive age with and without HIV in the Southern United States: baseline description from the STAR cohort.

Objectives: To explore the prevalence of depressive symptoms and associated factors among reproductive-aged women participating in the Study of Treatment and Reproductive outcomes (STAR) cohort.

Design: Cross-sectional analysis.

Methods: We analyzed baseline data from women with HIV (WWH) and women without HIV (WwoH) but at risk for HIV enrolled in the STAR, a prospective observational cohort of reproductive-aged women in six Southern U.

Social Functioning in Autistic Children with Below-Average vs. Average IQ: Limited Behavioral and Neural Evidence of Group Differences.

Despite the relatively high rates of intellectual disability (ID) in autism, research studies and clinical trials commonly exclude autistic participants with below-average IQ. This study aimed to characterize the effect of intellectual ability on social functioning in autistic adolescents assessed using behavioral and neural measures. Caregiver reports and direct standardized behavioral assessments of social abilities along with event-related potential measures of social and nonsocial information processing were obtained in school-age children with autism and ID (n = 41) matched on age, sex, and autism symptom severity to autistic participants with average IQ (n = 41).

Germline analysis of an international cohort of pediatric diffuse midline glioma patients.

Background: Factors that drive the development of diffuse midline gliomas (DMG) are unknown. Our study aimed to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline variants in pediatric patients with DMG.

Methods: We assembled an international cohort of 252 pediatric patients with DMG, including diffuse intrinsic pontine glioma (n=153), with germline whole genome or whole exome sequencing.

Platinum-based nanoalloys for the oxygen reduction reaction: exposing the true active phase techniques.

Platinum-based nanoalloys are efficient electrocatalysts for the oxygen reduction reaction (ORR). measurements have revealed that key properties including induced strain, chemical composition, coordination environment, evolve significantly during operation, which can hampertheir effective implementation in fuel cells. In fact, recent studies indicate that the impact of the early surface activation steps of Pt-based nanoalloys has been hitherto underestimated and is an important factor contributing to loss of their initial electroactivity.

Machine learning to predict urine culture antibiotic sensitivities in the emergency department.

Background: Urinary tract infections (UTIs) are among the most common bacterial infections diagnosed in the emergency department. Treatment of UTIs is largely empiric because urine culture results are not rapidly available.

Objectives: We examined whether machine learning could predict antibiotic sensitivities of the urine cultures by using only data available during the clinical encounter.

Consumers' perspectives on antibiotic use and antibiotic resistance in food animals: a systematic review.

Inappropriate antibiotic use in food animals is considered a significant contributor to increasing antibiotic resistance. Consumers can play a critical role in reducing it through purchasing choices, demand, and policy advocacy. This systematic review aimed to synthesize all published literature investigating consumers' perspectives (i.

Allele and transcriptome mining in Gossypium hirsutum reveals variation in candidate genes at genetic loci affecting cotton fiber quality and textile flammability.

Background: Breeding valuable traits in crop plants requires identifying diverse alleles in the germplasm that are likely to affect desirable characteristics. The genetic diversity of historic cultivars of cotton is a reservoir of potentially important genes for crop improvement and genetic research. Diversity in the characteristics of harvested cotton fibers affects their suitability for end-use applications.

In-situ forming solvent-induced phase inversion (SIPI) implants for controlled drug delivery: role of hydrophilic polymers.

In recent years, there has been a surge of research focused on in situ-forming implants as a method of localized drug delivery. Despite advancements, the predominant challenge in situ-forming solvent-induced phase inversion (SIPI) implants is significant burst release which typically occurs within the first 24 hours post-administration. Another notable challenge is the real-time characterization of these implants, which is crucial for understanding their in situ formation and degradation mechanism.

Patterns of Cannabis Use among Women With HIV in the United States.

Cannabis legalization in the United States changed cannabis product potency and consumption modalities. Women with HIV are an aging population with prevalent cannabis use twice that of national estimates. Because cannabis use may confer both health benefits and risks, it is important to understand cannabis use patterns among women with HIV.

TGFβ1 generates a pro-fibrotic proteome in human lung parenchyma that is sensitive to pharmacological intervention.

Introduction: Novel treatments for idiopathic pulmonary fibrosis (IPF) are needed urgently. A better understanding of the molecular pathways activated by TGFβ1 in human lung tissue may facilitate the development of more effective anti-fibrotic medications. This study utilized proteomic analysis to test the hypothesis that TGFβ1 induces pro-fibrotic effects on human lung parenchyma proteome, and to evaluate the viability of this model for testing novel therapeutic targets.

Comparative impact of sunlight and salinity on human pathogenic virus survival in river, estuarine, and marine water microcosms.

Urban wastewater contains a diverse array of human pathogenic viruses, often in high concentrations, presenting a significant challenge for water quality management. Sewage spills into natural water systems therefore pose a significant public health risk due to the potential to cause viral infections, yet the behaviour of viruses under dynamic environmental conditions remains poorly understood. This study investigates the decay of sewage-associated viruses (Adenovirus, Enterovirus, Hepatitis A Virus, Influenza A Virus, Norovirus GII, and Respiratory Syncytial Virus) in river, estuary, and marine water, with and without simulated sunlight.

Low-dose acidification of cattle slurry with sulfuric acid enhances oilseed-rape yield but risks elevated sulfide formation during prolonged storage.

Slurry acidification using sulfuric acid (HSO) is an effective strategy for reducing ammonia and methane emissions during storage while providing a valuable source of sulfur (S) for crops. However, the optimal HSO dose for balancing emission mitigation, S availability, and cost-effectiveness remains unclear, particularly concerning the formation of undesirable sulfides during storage. This study investigated the effects of HSO dose on S transformations during storage of cattle slurry (CS), anaerobically digested slurry (DS), the liquid fraction of separated digested slurry (LFDS), and the subsequent S fertilizer replacement value (SFRV) for oilseed rape (OSR).

Sometimes, Only Some Siblings Go to Foster Care: Exploring Split Sibling Groups in a Nationwide Sample.

Research on sibling separation in foster care often focuses on cases where all siblings are removed. However, separation can also occur when only some children are placed in care, a scenario that is underexplored. This study investigates: the frequency of partial sibling placements; differences between placed and non-placed siblings, as well as split versus intact sibling groups; and the risk of re-report and future placement for non-placed children in split groups compared to those in intact groups.

Studying the effects of polymers on therapeutic deep eutectic solvents' formation and stability: A thermal analysis-based approach to optimise polymer selection.

Therapeutic deep eutectic solvents (THEDES) are the liquids produced upon mixing two solid materials, where at least one of them is an active pharmaceutical ingredient. The strong hydrogen bonding (HB) between the parent materials is the reason for such profound depression in their melting points. THEDES formation can improve drugs' solubility and permeation characteristics.

Regulation of MLO trafficking by calmodulin binding domains.

Flowering plant sexual reproduction relies on the communication between the pollen tube and synergid cells to induce pollen tube bursting. During this process, the MILDEW RESISTANCE LOCUS-O (MLO) protein NORTIA (NTA) is polarly trafficked from the Golgi, where it is inactive, to the filiform apparatus, where it is functional in synergids. MLOs were recently described as calcium channels and have been proposed to be negatively regulated through calmodulin (CaM) binding at a conserved C-terminal calmodulin binding domain (CaMBD).

Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.

Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host.

Pharmacometabolomics in TB meningitis-Understanding the pharmacokinetic, metabolic, and immune factors associated with anti-TB drug concentrations in cerebrospinal fluid.

Poor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver of morbidity and mortality in TB meningitis (TBM). While the amount of a particular drug that crosses into the cerebrospinal fluid (CSF) varies from person to person, little is known about the host factors associated with interindividual differences in CSF concentrations of anti-TB drugs. In patients diagnosed with TBM from the country of Georgia (n = 17), we investigate the association between CSF concentrations of anti-TB antibiotics and multiple host factors including serum drug concentrations and CSF concentrations of metabolites and cytokines.

Brain aging shows nonlinear transitions, suggesting a midlife "critical window" for metabolic intervention.

Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal "landmarks" of brain aging starting in midlife (40s).

A Syntenic Pangenome for Reveals Taxonomic Boundaries and Stratification of Metabolic and Virulence Potential across Species.

Bacterial vaginosis (BV) is a prevalent condition associated with an imbalance in the vaginal microbiota, often involving species of . The taxonomic complexity and inconsistent nomenclature of have impeded progress in understanding the role of specific species in health and disease. In this study, we conducted a comprehensive genomic and pangenomic analysis to resolve taxonomic ambiguities and elucidate metabolic and virulence potential across species.

myRESEARCHpath: An Interactive Tool for Investigators and Research Administrators.

Research-intensive institutions rely on specialized central offices to support research administrators and investigators through various processes and requirements. This helps researchers successfully and compliantly conduct and manage research. However, when these support offices communicate their processes and resources from disparate locations, it can be challenging for research administrators and investigators to locate what they need at the time they need it, and to understand how this information relates with that provided by other research support offices.