Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

VIEWER: an extensible visual analytics framework for enhancing mental healthcare.

Objective: A proof-of-concept study aimed at designing and implementing Visual & Interactive Engagement With Electronic Records (VIEWER), a versatile toolkit for visual analytics of clinical data, and systematically evaluating its effectiveness across various clinical applications while gathering feedback for iterative improvements.

Materials And Methods: VIEWER is an open-source and extensible toolkit that employs natural language processing and interactive visualization techniques to facilitate the rapid design, development, and deployment of clinical information retrieval, analysis, and visualization at the point of care. Through an iterative and collaborative participatory design approach, VIEWER was designed and implemented in one of the United Kingdom's largest National Health Services mental health Trusts, where its clinical utility and effectiveness were assessed using both quantitative and qualitative methods.

Probing Autism and ADHD subtypes using cortical signatures of the T1w/T2w-ratio and morphometry.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental conditions that share genetic etiology and frequently co-occur. Given this comorbidity and well-established clinical heterogeneity, identifying individuals with similar brain signatures may be valuable for predicting clinical outcomes and tailoring treatment strategies. Cortical myelination is a prominent developmental process, and its disruption is a candidate mechanism for both disorders.

Improving Adherence to National Institute for Health and Care Excellence (NICE) Guidelines for the Use of Tranexamic Acid in Primary Total Knee Arthroplasty: A Quality Improvement Initiative.

Background: Tranexamic acid (TXA) is a pharmacological agent used in reducing blood loss during orthopaedic surgeries, including total knee arthroplasty (TKA). Despite its proven efficacy and National Institute for Health and Care Excellence (NICE) guidelines recommending combined topical and intravenous administration, compliance in clinical practice often lags.

Objective: This study aimed to evaluate and improve adherence to NICE guidelines for TXA use during TKA through a quality improvement initiative.

Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on erythromelalgia in youth, 2) identify knowledge gaps, and 3) inform directions for future research in pediatric erythromelalgia. One hundred and sixty-seven studies reporting 411 cases of childhood-onset erythromelalgia were identified.

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study.

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the -related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design: Prospective natural history study.

Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

Structural variation in nebulin and its implications on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.

Introduction: Structural variants (SVs) of the nebulin gene (), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in .

Psychological impact of an intensive care admission for COVID-19 on patients in the United Kingdom.

Background: The psychological impact of surviving an admission to an intensive care unit (ICU) with COVID-19 is uncertain. The objective of the study was to assess the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in ICU survivors treated for COVID-19 infection, and identify risk factors for psychological distress.

Methods: This observational study was conducted at 52 ICUs in the United Kingdom.

Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.

Patient cost analysis of a community-based teledermatology service versus conventional outpatient appointments in East Kent: a retrospective study through a societal lens to reduce health inequalities.

Background: The UK's National Health Service (NHS) is grappling with rising demand and limited dermatologists, leading to longer waiting times. This is particularly concerning for conditions like malignant melanoma, where early diagnosis is crucial. Teledermatology is being introduced to address these issues, but its impact on patients' monetary and time costs, especially in deprived areas, is under-researched.

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).

Giant Duodenal Brunneroma: Report of a Rare Case and Review of the Literature.

BACKGROUND Brunneromas are among the rarest benign tumors of the upper gastrointestinal tract. They arise from the Brunner's glands and patients have a good prognosis if treated timely and radically. Because symptoms are rare, their diagnosis can be challenging, especially regarding the smaller ones.

Improving Patient Care and Streamlining Follow-Up: Compliance With National Institute for Health and Care Excellence (NICE) Guidelines for Pediatric Distal Radius Buckle Fractures.

Introduction: Torus fractures, also known as buckle fractures, are among the most common types of fractures seen in children who present to the emergency department (ED). These injuries usually occur when a child falls onto an outstretched hand, resulting in the compression and buckling of the dorsal cortex of the radius while the volar cortex remains intact. These fractures generally have a good prognosis and heal well with simple immobilization with a low risk of complications.

Bleed treatment with eptacog beta (rFVIIa) results in a low incidence of rebleeding in adult and adolescent patients with haemophilia A or B with inhibitors.

Introduction: Eptacog beta is a novel human recombinant FVIIa approved for use in the United States, European Union, United Kingdom and Mexico for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors (≥12 years). It is also indicated for perioperative care in the same patient population in Europe and the United Kingdom.

Aim: To assess the incidence of rebleeding and review treatment outcomes in subjects with haemophilia with inhibitors enrolled in the phase 3 PERSEPT 1 clinical trial.

Evaluating Renal Disease in Pediatric-Onset Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Disease Course, Outcomes, and Predictors of Outcome.

Objective: We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys.

Methods: Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or ANCA-positive pauci-immune glomerulonephritis, were 18 years or younger at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and at either 12 or 24 months. Ambispective data from A Registry for Children with Vasculitis/Pediatric Vasculitis Initiative Registry was used.

Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study.

Several international pharmacovigilance agencies have issued warnings regarding the potential risk of myasthenia gravis (MG) following statin therapy. Our study investigated this association using population-based electronic health records in Hong Kong. We conducted a sequence of target trial emulation (TTE) for interpersonal comparison and a self-controlled case series (SCCS) study for intrapersonal comparison.

Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases.

Background: Nephronophthisis (NPHP) is an autosomal recessive genetic disorder that can cause early-onset kidney failure. plays an important role in early kidney development and encodes a protein that interacts with other proteins within the primary cilium. mutations are known to cause nephronophthisis 16 (NPHP-16).

Sex differences in myocardial infarction care and outcomes: a longitudinal Scottish National Data-Linkage Study.

Aims: We investigate sex disparities in management and outcomes of myocardial infarction (MI) in contemporary practice in Scotland.

Methods And Results: This was a longitudinal cohort study including all MI admissions aged 45-80 years across Scotland between 2010-2016 and 2:1 age, sex, and general practice-matched general population controls. Participants were followed up until the end of 2021.

Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.

Background: Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes.

Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.

Phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex are rare conditions, which each increases risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection, and multidisciplinary care. In this article, we present updated surveillance recommendations and considerations for children and adolescents with phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex and provide suggestions for further research in each of these conditions.