Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Relationships between hearing, auditory processing, and communication in children diagnosed with auditory neuropathy spectrum disorder.

Objectives: The objectives of this study were to evaluate the relationships between auditory processing, speech discrimination, and listening and communication abilities in children diagnosed with auditory neuropathy spectrum disorder (ANSD) compared to those with normal hearing.

Methods: This was a case-control study involving seventeen participants with a diagnosis of ANSD who used spoken language as their primary mode of communication and wore hearing aids or were unaided and 21 normally hearing controls. All underwent a battery of behavioural measures of hearing, speech perception and auditory processing skills.

Systematic review of integrated mental and physical health services for children and young people with eating and functional symptoms.

Background: Evidence suggests that by recognising the psychosocial component of illness as equally important to the biological components, care becomes more holistic, and patients can benefit. Providing this type of care requires collaboration among health professionals, rather than working in isolation, to achieve better outcomes. However, there is a lack of evidence about the implementation of integrated health care.

Generation of a human induced pluripotent stem cell line (CRICKi021-A) from a patient with Ullrich congenital muscular dystrophy carrying a pathogenic mutation in the COL6A1 gene.

Ullrich congenital muscular dystrophy (UCMD) represents the most severe subtype of collagen VI-related dystrophies (COL6-RDs), a spectrum of rare extracellular matrix disorders affecting skeletal muscle and connective tissue. Here, we generated an induced pluripotent stem cell (iPSC) line (CRICKi021-A) from a UCMD patient with de novo dominant-negative mutation in COL6A1 gene by reprogramming dermal fibroblasts using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed pluripotency-associated markers and differentiated into the three germ layers.

A scoping review of the electronic collection and capture of patient reported outcome measures for children and young people in the hospital setting.

Patient reported outcome measures (PROMs) capture patients' views of their health status and the use of PROMs as part of standard care of children and young people has the potential to improve communication between patients/carers and clinicians and the quality of care. Electronic systems for the collection of or access to PROMs and integrating PROMs into electronic health records facilitates their implementation in routine care and could help maximise their value. Yet little is known about the technical aspects of implementation including the electronic systems available for collection and capture and how this may influence the value of PROMs in routine care which this scoping review aims to explore.

Integration of physical and mental health services for children and young people with eating disorders and functional symptom disorders: discrete choice experiment.

Background: Given the increasing recognition of the value of greater integration of physical and mental health services for children and young people, we aimed to evaluate preferences among parents for the characteristics associated with integrated health service provision for two conditions (eating disorders, functional symptom disorders).

Methods: Two discrete choice experiments (DCEs) were conducted, using electronic surveys. Participants were adult parents of children and young people.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Evaluation of Phoenix Sepsis Score Criteria: Exploratory Analysis of Characteristics and Outcomes in an Emergency Transport PICU Cohort From the United Kingdom, 2014-2016.

Objectives: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

Design: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

Setting: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

Guided Self-Help Treatment for Children and Young People With Eating Disorders: A Proof-Of-Concept Pilot Study.

Objective: To conduct a proof-of-concept pilot study of a CBT guided self-help intervention for children and young people with eating disorders.

Method: Children and young people were recruited from two outpatient eating disorder services in England. They received a CBT guided self-help intervention consisting of eight modules and weekly support sessions.

Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is an autoimmune condition which causes significant morbidity in children and young adults and is more severe in its presentation than adult-onset SLE. While many aspects of immune dysfunction have been studied extensively in adult-onset SLE, there is limited and contradictory evidence of how cytotoxic CD8+ T cells contribute to disease pathogenesis and studies exploring cytotoxicity in JSLE are virtually non-existent. Here, we report that CD8+ T cell cytotoxic capacity is reduced in JSLE versus healthy controls, irrespective of treatment or disease activity.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Reverse-engineering the Venus figurines: An eco-life-course hypothesis for the aetiology of obesity in the Palaeolithic.

Evolutionary perspectives on obesity have been dominated by genetic frameworks, but plastic responses are also central to its aetiology. While often considered a relatively modern phenomenon, obesity was recorded during the Palaeolithic through small statuettes of the female form (Venus figurines). Even if the phenotype was rare, these statuettes indicate that some women achieved large body sizes during the last glacial maximum, a period of nutritional stress.

Investigating the pathogenicity of the recessive p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells.

Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, mutations are the most common, and their diagnosis allows the use of alternative therapies, including sulfonylureas. In an earlier study, we described a variant displaying recessive transmission, p.

Editorial Perspective: How can we develop effective and timely interventions for young people with chronic loneliness?

Loneliness is an adaptive experience evolved to create motivation to engage in social relationships. However, for some young people, loneliness can become chronic which can have serious negative health consequences. Despite this, there is a relative lack of evidence for interventions.

Associations of body composition at birth and accretion from 0 to 5 years with kidney function and volume at the 10-year follow-up: the Ethiopian Infant Anthropometry and Body Composition birth cohort.

Background: Fat mass (FM) and fat-free mass (FFM) in early life are associated with later obesity and cardiometabolic disease.

Objectives: This study aimed to assess the associations of FM and FFM at birth and conditional FM and FFM accretion from 0 to 5 y with kidney outcomes at the 10-y follow-up.

Methods: The Ethiopian Infant Anthropometry and Body Composition birth cohort included term infants born in Jimma town, with a birth weight ≥1500 g, and having no congenital malformations.

Ages and Stages Questionnaires in the assessment of young children after cardiac surgery.

Aims: This study explored the prospective use of the Ages and Stages Questionnaires-3 in follow-up after cardiac surgery.

Materials And Method: For children undergoing cardiac surgery at 5 United Kingdom centres, the Ages and Stages Questionnaires-3 were administered 6 months and 2 years later, with an outcome based on pre-defined cut-points: Red = 1 or more domain scores >2 standard deviations below the normative mean, Amber = 1 or more domain scores 1-2 standard deviations below the normal range based on the manual, Green = scores within the normal range based on the manual.

Results: From a cohort of 554 children <60 months old at surgery, 306 participated in the postoperative assessment: 117 (38.

Associations of early childhood exposure to severe acute malnutrition and recovery with cardiometabolic risk markers in later childhood: 5-year prospective matched cohort study in Ethiopia.

Background: Impaired fetal and accelerated postnatal growth are associated with cardiometabolic disease. Few studies investigated how recovery from severe acute malnutrition (SAM) is associated with childhood cardiometabolic risk.

Objectives: We evaluated cardiometabolic risk in children with SAM treated through community-based management, relative to controls, 5-y postrecovery.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Association between birth length, linear growth velocities, and primary school achievement at age 10 years: evidence from the Ethiopian iABC birth cohort.

Background: Childhood is a period marked by dynamic growth. Evidence of the association between childhood linear growth and school achievement comes mostly from cross-sectional data. We assessed associations between birth length, childhood linear growth velocities, and stunting with school achievement.

Efficient assay for evaluating drug efficacy and synergy against emerging SARS-CoV-2 strains.

Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, antiviral combinations may be more potent and lead to faster viral clearance, but the methods for screening antiviral combinations against respiratory viruses are not well established and labor-intensive. Here, we describe a time-efficient (72-96 h) and simple drug-sensitivity assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using standard 96-well plates.

Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016.

Background: The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.

Methods: The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy.