An update on multiple breath washout in children with cystic fibrosis.

Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane regulator (CFTR) gene, leading to progressive lung disease and systemic complications. Lung disease remains the primary cause of morbidity and mortality, making early detection of lung function decline crucial. The Lung Clearance Index (LCI), derived from the multiple breath washout (MBW) test, has emerged as a sensitive measure for identifying early airway disease.

RORA-neurodevelopmental disorder: a unique triad of developmental disability, cerebellar anomalies, and myoclonic seizures.

Purpose: RORA encodes the RAR-related orphan receptor-α (RORα), playing a pivotal role in cerebellar maturation and function. Here, we report the largest series of individuals with RORA-related-neurodevelopmental disorder (RORA-NDD).

Methods: Forty individuals (30 unrelated; 10 siblings from 4 families) carrying RORA pathogenic/likely pathogenic variants were collected through an international collaboration.

An innovative Community Mobilisation and Community Incentivisation for child health in rural Pakistan (CoMIC): a cluster-randomised, controlled trial.

Background: Infectious diseases remain the leading cause of death among children younger than 5 years due to disparities in access and acceptance of essential interventions. The Community Mobilisation and Community Incentivisation (CoMIC) trial was designed to evaluate a customised community mobilisation and incentivisation strategy for improving coverage of evidence-based interventions for child health in Pakistan.

Methods: CoMIC was a three-arm cluster-randomised, controlled trial in rural areas of Pakistan.

Evaluating post-cardiac arrest blood pressure thresholds associated with neurologic outcome in children: Insights from the pediRES-Q database.

Background: Current Pediatric Advanced Life Support Guidelines recommend maintaining blood pressure (BP) above the 5th percentile for age following return of spontaneous circulation (ROSC) after cardiac arrest (CA). Emerging evidence suggests that targeting higher thresholds, such as the 10th or 25th percentiles, may improve neurologic outcomes. We aimed to evaluate the association between post-ROSC BP thresholds and neurologic outcome, hypothesizing that maintaining mean arterial pressure (MAP) and systolic blood pressure (SBP) above these thresholds would be associated with improved outcomes at hospital discharge.

Chromosome X-wide common variant association study in autism spectrum disorder.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.

Introduction to immunology and immune disorders.

The body has a collection of physical barriers to prevent infection, but once these are overcome, we rely on our immune systems to protect us against a wide variety of infections. The complex mechanisms through which this is achieved are grouped into two lines of defense called the "innate" and "adaptive" immune systems. The innate immune system provides a rapid and tailored response to infection or injury often associated with inflammation.

Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.

Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD).

The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

Generating 3D brain tumor regions in MRI using vector-quantization Generative Adversarial Networks.

Medical image analysis has significantly benefited from advancements in deep learning, particularly in the application of Generative Adversarial Networks (GANs) for generating realistic and diverse images that can augment training datasets. The common GAN-based approach is to generate entire image volumes, rather than the region of interest (ROI). Research on deep learning-based brain tumor classification using MRI has shown that it is easier to classify the tumor ROIs compared to the entire image volumes.

Lung Function Recovery from Pulmonary Exacerbations Treated with Oral Antibiotics in Primary Ciliary Dyskinesia.

Rationale: Patients with Primary Ciliary Dyskinesia (PCD) experience acute pulmonary exacerbations (PEx). In Cystic Fibrosis (CF), PEx treated with oral antibiotics (oPEx) were found to be related to short and long-term lung function deficits, however the impact oPEx on lung function in patients with PCD has not yet been assessed.

Objective: To assess the impact of oPEx on lung function recovery in PCD and determine the factors associated with poorer response.

Exome and Genome Sequencing to Diagnose the Genetic Basis of Neonatal Hypotonia: An International Consortium Study.

Background And Objectives: Hypotonia is a relatively common finding among infants in the neonatal intensive care unit (NICU). Consideration of genetic testing is recommended early in the care of infants with unexplained hypotonia. We aimed to assess the diagnostic yield and overall impact of exome and genome sequencing (ES and GS).

Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies.

In this review, we provide an overview of food allergy genetics and epigenetics aimed at clinicians and researchers. This includes a brief review of the current understanding of genetic and epigenetic mechanisms, inheritance of food allergy, as well as a discussion of advantages and limitations of the different types of studies in genetic research. We specifically focus on the results of genome-wide association studies in food allergy, which have identified 16 genetic variants that reach genome-wide significance, many of which overlap with other allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis.

The adoption and compliance to central line-associated bloodstream infection insertion and maintenance bundle programs in intensive care unit settings across Canada.

Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.

Deep superpixel generation and clustering for weakly supervised segmentation of brain tumors in MR images.

Purpose: Training machine learning models to segment tumors and other anomalies in medical images is an important step for developing diagnostic tools but generally requires manually annotated ground truth segmentations, which necessitates significant time and resources. We aim to develop a pipeline that can be trained using readily accessible binary image-level classification labels, to effectively segment regions of interest without requiring ground truth annotations.

Methods: This work proposes the use of a deep superpixel generation model and a deep superpixel clustering model trained simultaneously to output weakly supervised brain tumor segmentations.

Metastatic conjunctival melanoma: a multicentre international study.

Background: To reveal clinical findings related to metastatic conjunctival melanoma.

Methods: 10 ophthalmic oncology centres (9 countries and 4 continents) shared data to create a large clinical case series. The main outcome measures were the incidence and cumulative risk of systemic metastasis, study mortality rates and Kaplan-Meier patient mortality after developing conjunctival melanoma metastasis.

Interleukin 8-CXCR2 mediated neutrophil extracellular trap (NET) formation in biliary atresia associated with NET-Induced stellate cell activation.

Background Aims: Biliary atresia (BA) entails an inflammatory sclerosing lesion of the biliary tree, with prominent fibrosis in infancy. Previous studies revealed neutrophil-activating IL-8 and neutrophil extracellular traps (NETs) positively correlated with bilirubin and risk of liver transplant. The aims of this study were to determine the mechanism of NET formation (NETosis) in BA and if NETs induce stellate cell activation.

Hospitalizations for Eating Disorders and Other Mental, Behavioral, and Neurodevelopmental Disorders Before and During COVID-19 in Canada.

Purpose: We assessed hospital admission rates for anorexia nervosa (AN)/atypical AN (AAN) relative to other mental, behavioral, and neurodevelopmental disorders across age groups before and 1-year postpandemic onset.

Methods: Using the Canadian Discharge Abstracts Database, we analyzed admissions for AN/AAN and mental, behavioral, and neurodevelopmental disorders in ages 10-84-year-olds, grouped into 10-24, 25-44, and 45+ year olds. Data spanned fiscal years (FY) 2006-2021.

Application of Youth-Led Participatory Action Research to Examining Adolescent Sexual and Reproductive Health and Rights in Ontario: What Can We Learn?

Engaging adolescents and young people as partners in research is increasingly acknowledged as a vital strategy to ensure diverse voices are heard and to catalyze social change. This article, coauthored by adolescent and adult researchers, presents the methodological approach and outcomes of a youth-led participatory action research (YPAR) study in which three teams of youth researchers developed and implemented projects examining equity-related factors affecting adolescent sexual and reproductive health and rights (ASRHR) in Ontario, Canada. Teams of four assigned-female youth researchers aged 16-19 years were recruited from three priority regions through purposive sampling.