Hilbert transform analysis of the mouse scotopic electroretinogram reveals two distinct bursts of oscillatory potentials with progressively dimmer flashes.

Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG).

Methods: Scotopic ERGs [Intensity: - 6.3 to 0.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Comparative Efficacy of Nonsteroid Immunosuppressive Medications in Childhood Nephrotic Syndrome.

Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity.

Child- and Proxy-reported Differences in Patient-reported Outcome and Experience Measures in Pediatric Surgery: Systematic Review and Meta-analysis.

Purpose: Pediatric health outcomes are often assessed using proxy reports, which may not fully capture children's experiences. Children with surgical conditions face unique, changing healthcare journeys, making accurate representation challenging. This review compares child-reported health status and treatment experiences from Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) with parent reports.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries.

Objective: To assess variability among data elements collected among existing neonatal hypoxic-ischemic encephalopathy (HIE) data registries worldwide and to determine the need for future harmonization of standard common data elements.

Study Design: This was a cross-sectional study of data elements collected from current or recently employed HIE registry data forms. Registries were identified by literature search and email inquiries to investigators worldwide.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022).

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Machine-learning-assisted Preoperative Prediction of Pediatric Appendicitis Severity.

Purpose: This study evaluates the effectiveness of machine learning (ML) algorithms for improving the preoperative diagnosis of acute appendicitis in children, focusing on the accurate prediction of the severity of disease.

Methods: An anonymized clinical and operative dataset was retrieved from the medical records of children undergoing emergency appendectomy between 2014 and 2021. We developed an ML pipeline that pre-processed the dataset and developed algorithms to predict 5 appendicitis grades (1 - non-perforated, 2 - localized perforation, 3 - abscess, 4 - generalized peritonitis, and 5 - generalized peritonitis with abscess).

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Birthing parent adverse childhood experiences and risk of atopic diseases in 5-year-old children.

Following up on previous findings from the All Our Families (AOF) cohort, the current study investigated the relationship between birthing parent history of adverse childhood experiences (ACEs) and child atopy, including asthma, allergy, and eczema, at five years of age. Potential indirect effects were explored. Participants completed the ACEs scale, validated questionnaires of anxiety and depression symptoms, and reported on their and their children's atopic disease history.

Cost-effectiveness of watchful waiting versus immediate emergency department transfer after epinephrine autoinjector use in Canada.

Background: Until recently, immediate emergency department (ED) transfer after food-related anaphylactic reactions was recommended regardless of symptom resolution following use of an epinephrine autoinjector (EAI). We evaluated the cost-effectiveness of delayed ED transfer after EAI use in non-medical settings (watchful waiting) compared to immediate ED transfer among pediatric patients with food allergies in Canada.

Methods: We developed a probabilistic Markov model of individuals starting at age of one year who are at risk of severe food-related allergic reactions requiring epinephrine.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Neuroimaging stratification reveals the striatal vulnerability to stress as a risk for schizophrenia.

The striatum, a core brain structure relevant for schizophrenia, exhibits heterogeneous volumetric changes in this illness. Due to this heterogeneity, its role in the risk of developing schizophrenia following exposure to environmental stress remains poorly understood. Using the putamen (a subnucleus of the striatum) as an indicator for convergent genetic risk of schizophrenia, 63 unaffected first-degree relatives of patients (22.

Brain surface area and function alterations are correlated with cognition in patients with end-stage renal disease.

Background: Cognitive decline may occur in patients with end-stage renal disease (ESRD), and is particularly severe in patients with ESRD undergoing hemodialysis; however, the mechanism of this relationship between cognitive decline and ESRD is unclear. Cortical-based structural and functional analysis can be used to understand these cortical changes and their relationship with cognitive decline in non-dialysis and maintenance dialysis ESRD patients. This study aimed to examine whether there was any correlation between alterations in cortical and resting-state function changes and cognitive decline in patients diagnosed with ESRD.

Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program.

Importance: Detection of congenital cytomegalovirus (cCMV) infection has previously relied on targeted screening programs or clinical recognition; however, these approaches miss most cCMV-infected newborns and fail to identify those infants who are asymptomatic at birth but at risk for late-onset sensorineural hearing loss.

Objective: To determine the feasibility of using routinely collected newborn dried blood spots (DBS) in a population-based cCMV screen to identify infants at risk for hearing loss and describe outcomes of infants screened.

Design, Setting, And Participants: This diagnostic study of a population-based screening program in Ontario, Canada, took place from July 29, 2019, to July 31, 2023.

High risk of drug-resistant tuberculosis in IGRA-negative contacts: should preventive treatment be considered?

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M.

Neutrophil-to-lymphocyte ratio at diagnosis predicts colonoscopic activity in pediatric inflammatory bowel diseases (pIBD).

Background: Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel diseases (IBD) in adults, but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predicted hospitalization, surgery, and therapy response by 52 weeks.

Sudden Onset of Unexplained Leg Pain Following Open Reduction and Internal Fixation of a Displaced Tibial Tuberosity Fracture: A Case Report of Deep Venous Thrombosis in an Adolescent Athlete.

This case report presents a 16-year-old basketball player, who developed deep venous thrombosis (DVT) following surgical intervention for a displaced tibial tuberosity fracture and forearm fractures. Despite few identifiable thrombotic risk factors, the patient's postoperative course was complicated by unexplained leg pain, fever, and ultimately confirmed DVT. Prompt management with therapeutic anticoagulation and multidisciplinary care led to favourable outcomes.

Improving access to services in neuro-developmental disability: proceedings of a national meeting to advance community capacity.

As part of a participatory project to advance navigational service delivery systems for children with neurodevelopmental disability (NDD) and their families, this paper addresses proceedings from a capacity-building conference in Vancouver, Canada. A total of 29 invited key stakeholders attended the meeting with the following aims: knowledge sharing amongst provincial/territorial regions advancing NDD navigation capacity; sustainable action-oriented knowledge exchange; and operationalizing next steps to build navigation resources across Canadian regions. Regional representation included multiple and inter-sectoral partners (e.

Reimagining apnea monitoring in the neonatal ICU.

Purpose Of Review: This review outlines the prevalence and complications of apneas and intermittent hypoxemic events in preterm infants, examines current monitoring limitations in neonatal ICUs (NICUs), and explores emerging technologies addressing these challenges.

Recent Findings: New evidence from the Prematurity-Related Ventilatory Control (Pre-Vent) study, which analyzed cardiorespiratory data from 717 extremely preterm infants, exposes the varying frequency, duration, and severity of apneas, intermittent hypoxemia, bradycardias, and periodic breathing during hospitalization, and highlights the negative impact of intermittent hypoxemia on pulmonary outcomes at discharge. Although traditional monitoring methods cannot differentiate between apnea types and quantify their burden, recent advancements in sensor technologies and data integration hold promise for improving real-time detection and evaluation of apneas in the NICU.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.