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.

The association between total social exposure and incident multimorbidity: A population-based cohort study.

Background: Multimorbidity, the co-occurrence of two or more chronic conditions, is associated with the social determinants of health. Using comprehensive linked population-representative data, we sought to understand the combined effect of multiple social determinants on multimorbidity incidence in Ontario, Canada.

Methods: Ontario respondents aged 20-55 in 2001-2011 cycles of the Canadian Community Health Survey were linked to administrative health data ascertain multimorbidity status until 2022.

Understanding social behaviours across neurodiverse young people: roles of social cognition and self-regulation.

Background: Differences in social behaviours are common in young people with neurodevelopmental conditions (NDCs). Recent research challenges the long-standing hypothesis that difficulties in social cognition explain social behaviour differences.

Aims: We examined how difficulties regulating one's behaviour, emotions and thoughts to adapt to environmental demands (i.

Homozygous missense variant in causes early-onset neurodegeneration, leukoencephalopathy and autoinflammation.

Biallelic pathogenic variants in cause a fatal autosomal recessive multisystem disorder characterized by recurrent autoinflammation, hypomyelination, progressive neurodegeneration, microcephaly, failure to thrive, liver dysfunction, respiratory chain defects and accumulation of glycogen in skeletal muscle. No missense variants in have been reported to date.We report a 6-year-old boy with microcephaly, global developmental delays, lower limb spasticity with hyperreflexia, epilepsy, abnormal brain MRI, failure to thrive, recurrent fevers and transaminitis.

Minimally important change on the Columbia Impairment Scale and Strengths and Difficulties Questionnaire in youths seeking mental healthcare.

Background: Evidence-based mental health requires patient-relevant outcome data, but many indicators lack clinical meaning and fail to consider youth perceptions. The minimally important change (MIC) indicator designates change as meaningful to patients, yet is rarely reported in youth mental health trials.

Objective: This study aimed to establish MIC thresholds for two patient-reported outcome measures (PROMs), the Columbia Impairment Scale (CIS) and the Strengths and Difficulties Questionnaire (SDQ), using different estimation methods.

The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.

Survival Outcomes for Adolescent and Young Adults With Cancer in Low- and Middle-Income Countries: A Systematic Review.

Purpose: Patients with adolescent and young adult (AYA) cancer are recognized as a vulnerable subpopulation in high-income countries (HICs). Although survival gaps between HIC and low- and middle-income country (LMIC) children with cancer are well described, LMIC AYAs have been neglected. We conducted a systematic review to describe cancer outcomes among LMIC AYAs.

Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and a review of the first 3 years.

Purpose: Universal newborn hearing screening (UNHS) programs using audiometric techniques alone are limited in ability to detect non-congenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors: congenital cytomegalovirus (cCMV) and 22 common variants in GJB2 and SLC26A4. Here we describe our experience with genetic risk factor screening.

Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia.

Background: Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive.

Methods: We used placentae from normotensive and preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like cells, and placenta-specific preeclamptic mice.

Comorbidity between internalizing symptoms and disordered eating is primarily driven by genetic influences on emotion regulation in adult female twins.

Internalizing (e.g., anxiety, depression) and disordered eating (DE; e.

Achieving reliable patient reported outcomes collection to measure health care improvement in a learning health network: lessons from pediatric rheumatology care and outcomes improvement network.

Introduction: Data from the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry suggests that reliable collection of patient-reported outcomes (PROs) varies across sites. The objective of this study was to better understand the practices of collecting PROs at PR-COIN sites.

Methods: A REDCap survey was sent to the lead representative for each PR-COIN site.

pyDeid: an improved, fast, flexible, and generalizable rule-based approach for deidentification of free-text medical records.

Objectives: Deidentification of personally identifiable information in free-text clinical data is fundamental to making these data broadly available for research. However, there exist gaps in the deidentification landscape with regard to the functionality and flexibility of extant tools, as well as suboptimal tradeoffs between deidentification accuracy and speed. To address these gaps and tradeoffs, we develop a new Python-based deidentification software, pyDeid.

The Association between Pregnancy Complications and Long-Term Maternal Cardiometabolic Health in the MIREC Cohort Study.

Context: During pregnancy, women who experience certain pregnancy complications show elevations in biomarkers of inflammation and insulin resistance; however, few studies have examined these cardiometabolic biomarkers in the decade following pregnancy.

Objective: To examine the association between pregnancy complications and cardiometabolic biomarkers 9 years postpartum including: blood pressure, blood lipids, body fat percentage, insulin resistance (glucose, insulin, proinsulin, C-peptide, HOMA-IR, HbA1c, leptin, adiponectin) and inflammation (hs-C-reactive protein).

Methods: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study (2008-2021) we determined 3 groups of pregnancy complications: 1) hypertensive disorders of pregnancy (HDP) (n=35); any pregnancy complication in the index pregnancy, defined as preterm birth, HDP, impaired glucose tolerance or gestational diabetes mellitus (GDM) (n=55); or self-reported recurrence of one of these pregnancy complications (n=19).

A meta-analysis of intravitreal ranibizumab versus laser photocoagulation for the treatment of retinopathy of prematurity.

Purpose: Laser photocoagulation (LPC) has been a traditional treatment for retinopathy of prematurity (ROP). However, intravitreal anti-VEGF agents such as bevacizumab and ranibizumab (IVR) have also been increasingly used. This meta-analysis aims to rigorously compare IVR to LPC in the treatment of ROP.

Top Ten epilepsy research priorities: A UK priority setting partnership.

Purpose: Research into epilepsy has experienced decades of chronic underfunding compared to other neurological conditions despite its prevalence and seriousness. To evidence the need for greater investment, the Epilepsy Research Institute (formerly Epilepsy Research UK) funded, led and managed a James Lind Alliance (JLA) Priority Setting Partnership (PSP). This "industry standard" methodology brings together healthcare professionals, patients, carers and patient group representatives to identify and prioritise research uncertainties within a defined area of health or care.

Primary diffuse leptomeningeal atypical teratoid/rhabdoid tumours (ATRT) of childhood: a molecularly characterised case report and literature review.

Background: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant central nervous system tumours, typically presenting in the posterior fossa of very young children. Prognosis remains poor despite current therapy, while tumorigenesis implicates both genomic and epigenetic dysregulation. Primary diffuse leptomeningeal (PDL) ATRT, characterised by the absence of an intraparenchymal mass lesion, is seldom reported but appears associated with a dismal outcome.

The impact of pediatric post-cardiac arrest care on survival: A multicenter review from the AHA get with the Guidelines®-resuscitation post-cardiac arrest care registry.

Aim: Adherence to post-cardiac arrest care (PCAC) recommendations is associated with improved outcomes for adults. We aimed to describe the survival impact of meeting American Heart Association (AHA) PCAC guidelines in children after cardiac arrest.

Methods: We conducted a retrospective study using Get With The Guidelines® Resuscitation's (GWTG®-R) registry to describe the PCAC of patients ≤ 18 years old who suffered an in-hospital or out-of-hospital cardiac arrest (IHCA or OHCA).

Sex-specific ultrasound imaging biomarkers of neurodegeneration in a mouse model.

Introduction: Early detection of neurodegeneration is essential for optimizing interventions. The highly reproducible progression of neurodegeneration in the decrepit () mouse allows investigation of early biomarkers and mechanisms of brain injury.

Methods: Using high-frequency ultrasound, the common carotid arteries of female and male and control mice were imaged longitudinally at time points bracketing the disease progression (50, 75, and 125 days of age) ( = 6 mice/group/sex).

Solution NMR goes big: Atomic resolution studies of protein components of molecular machines and phase-separated condensates.

The tools of structural biology have undergone remarkable advances in the past decade. These include new computational and experimental approaches that have enabled studies at a level of detail - and ease - that were not previously possible. Yet, significant deficiencies in our understanding of biomolecular function remain and new challenges must be overcome to go beyond static pictures towards a description of function in terms of structural dynamics.

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.

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.