Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

Background And Aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design And Setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures.

The level of cognitive functioning in school-aged children is predicted by resting EEG Directed Phase Lag Index.

Quantifying cognitive potential relies on psychometric measures that do not directly reflect cortical activity. While the relationship between cognitive ability and resting state EEG signal dynamics has been extensively studied in children with below-average cognitive performances, there remains a paucity of research focusing on individuals with normal to above-average cognitive functioning. This study aimed to elucidate the resting EEG dynamics in children aged four to 12 years across normal to above-average cognitive potential.

Parental and Medical Classification of Neurodevelopment in Children Born Preterm.

Background And Objectives: The likelihood and severity of neurodevelopmental impairment (NDI) affects critical health care decisions. NDI definitions were developed without parental perspectives. We investigated the agreement between parental vs medical classification of NDI among children born preterm.

Age-Related Choroidal Involution Is Associated with the Senescence of Endothelial Progenitor Cells in the Choroid.

Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated.

Blazing the Trail of Non-Invasive Prenatal Screening Expanded Use: Healthcare Providers' Perspectives.

Objective: Advancements in non-invasive prenatal screening (NIPS) could significantly alter prenatal screening by expanding the range of genetic conditions screened. This study aims to explore the perspectives of healthcare professionals (HCP) on the expanded use of NIPS and explore specifications for the inclusion of genetic conditions.

Method: Semi-structured interviews were conducted with Canadian HCPs who counsel pregnant individuals about NIPS.

Multifunctional Carbon Dots In Situ Confined Hydrogel for Optical Communication, Drug Delivery, pH Sensing, Nanozymatic Activity, and UV Shielding Applications.

Inspired by the emerging potential of photoluminescent hydrogels, this work unlocks new avenues for advanced biosensing, bioimaging, and drug delivery applications. Carbon quantum dots (CDs) are deemed particularly promising among various optical dyes, for enhancing polymeric networks with superior physical and chemical properties. This study presents the synthesis of CDs derived from Prunella vulgaris, a natural plant resource, through a single-step hydrothermal process, followed by their uniform integration into hydrogel matrices via an in situ free radical graft polymerization.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Association between maternal schizophrenia and risk of serious asthma exacerbations in childhood.

Background And Hypothesis: While maternal schizophrenia is linked to chronic childhood medical conditions, little is known about the risk of acute asthma exacerbations among children whose mothers have schizophrenia. This population-based study used health data for all of Ontario, Canada to evaluate whether having a mother with schizophrenia was associated with increased risk of asthma exacerbations.

Study Design: The study cohort included 385,989 children diagnosed with asthma from age 2 years onward, followed from the time of their asthma diagnosis up to a maximum of age 19 years.

Stimuli-responsive carrageenan-based biomaterials for biomedical applications.

Carrageenan-based biomaterials have attracted considerable attention in recent years due to their unique biological properties, including their biodegradability, compatibility, and lack of adverse effects. These biomaterials exhibit a variety of beneficial properties, such as antiviral, antitumor, and immunomodulatory effects, which set them apart from other polysaccharides. Stimuli-responsive carrageenan-based biomaterials have attracted particular attention due to their unique properties, such as reducing systemic toxicity and controlling drug release.

Molecular signatures associated with venous thromboembolism in children with acute lymphoblastic leukemia.

Background: Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).

Objectives: We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.

Patients/methods: Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis.

Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis.

Background: Worldwide, approximately 2 million children younger than 15 years of age are infected with multidrug-resistant (MDR) , with MDR tuberculosis developing in approximately 30,000 annually. Evidence from randomized, controlled trials on tuberculosis preventive treatment in persons exposed to MDR tuberculosis is lacking.

Methods: In this community-based, multisite, double-blind, cluster-randomized, placebo-controlled trial in South Africa, we assessed the efficacy and safety of levofloxacin as preventive treatment in children with household exposure to an adult with bacteriologically confirmed MDR pulmonary tuberculosis.

Efficacy and Safety of Dupilumab in Children With Peanut Allergy: A Multicenter, Open-Label, Phase II Study.

Background: Peanut allergy is a potentially life-threatening food allergy in children. This study explored whether dupilumab, a human monoclonal immunoglobulin (Ig)G4 antibody that blocks the activity of interleukin (IL)-4/IL-13, improved safety and desensitization to peanut exposure in children with peanut allergy.

Methods: A Phase II, 24-week, multicenter, single-arm, open-label, proof-of-concept study was conducted in the USA and Canada (NCT03793608).

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.

A novel variant associated with NEDDFSA and new ocular features: case report and review of literature.

Introduction: Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA) is a recently described syndromic disease linked to genetic variants. We present a novel variant associated with a phenotype of NEDDFSA in a pediatric patient presenting with multiple anomalies including bilateral congenital ptosis and blepharophimosis, floppy eyelids, telecanthus, downward palpebral slants, myopia, cryptorchidism, hallux valgus and developmental delay.

Methods: Genetic testing performed on a large panel revealed a likely pathogenic variant in the gene (heterozygous, c.

Genomic sequencing in paediatric oncology: navigating conflicting roles and responsibilities.

Background: This study explores the ethical and moral challenges faced by paediatric oncologists when they are informed of patient genomic results, particularly during molecular tumour boards (MTBs), highlighting the interplay between their clinic, research and expert roles.

Methods: This was an explanatory sequential mixed-methods study using a survey distributed to paediatric oncologists in Quebec followed by optional semi-structured interviews. Oncologists' attitudes and comfort levels with six hypothetical germline DNA results identified in a patient from a clinical vignette were assessed using Likert scales.

Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions.

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response.

VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years, but with little success. Here, we investigate a different approach to augment VEGFA bioavailability: by deleting the VEGFA decoy receptor VEGFR1 (also known as FLT1), one can achieve more physiological VEGFA concentrations. We find that after cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring.

Oscillometry in the diagnosis, assessment, and monitoring of asthma in children and adults.

Diagnosing asthma typically relies on clinical history, physical examination, and objective lung function test results. Spirometry, the gold standard for assessing lung function, is universally recommended for the diagnostic, assessment, and monitoring of asthma. It requires maximal respiratory effort that limits cooperation in certain populations and has limitations in detecting small airway dysfunction.

Ruminative thinking mediates the effects of exposure to adverse life events on psychotic-like experiences.

Introduction: A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e.

Coupling Pre- and Postnatal Infant Exposures with Physiologically Based Pharmacokinetic Modeling to Predict Cumulative Maternal Levetiracetam Exposure During Breastfeeding.

Background And Objective: Although breastfeeding ensures optimal infant development and maternal health, mothers taking medications may abandon breastfeeding because of uncertainties regarding toxicity to infants. Current methods in predicting infant risk to maternal medication exposure do not account for breastfeeding-related variability or in utero exposure via the umbilical cord (UC). Previously, our workflow integrated variability in infant anatomy and physiology, breast milk intake volume, and drug concentrations in breast milk using physiologically based pharmacokinetic (PBPK) modeling.

Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model.

Background: Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI.