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.

Pharmacological preventions and treatments for pericardial complications after open heart surgeries.

Background: Pericardial complications following cardiac surgery are common and debilitating, significantly impacting patients' survival. We performed this network meta-analysis to identify the most effective and safest preventions and treatments for pericardial complications following cardiac surgery.

Methods: We systematically searched PubMed/MEDLINE, EMBASE and Cochrane CENTRAL from inception to 22 January 2024.

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.

Long-term Mental Health Morbidity in Adult Survivors of COVID-19 Critical Illness - A Population-based Cohort Study.

Background: Survivorship after coronavirus disease 2019 (COVID-19) critical illness may be associated with important long-term sequelae, but little is known regarding mental health outcomes.

Research Question: What is the association between COVID-19 critical illness and new post-discharge mental health diagnoses.

Study Design: AND METHODS: We conducted a population-based cohort study in Ontario, Canada (January 1, 2020-March 31, 2022).

Phase II Randomized Trial of BI 730357, a Novel Oral RORγt Inhibitor, for Moderate-to-Severe Plaque Psoriasis.

Trial Design: This two-part, double-blinded trial assessed the truncated retinoic acid-related orphan receptor γ (RORγt) inhibitor BI 730357 in plaque psoriasis.

Methods: Part 1: patients were randomized 2:2:2:2:1 to BI 730357 25, 50, 100, 200 mg, or placebo once daily (qd; fasting conditions); non-responders switched to higher doses. Part 2: a separate patient set was randomized 4:4:1 to BI 730357 400 mg qd, 200 mg twice daily, or placebo (fed conditions).

Malperfusion in Patients with Acute Type A Aortic Dissection: A Nationwide Analysis.

Background: This study describes in detail the clinical burden of malperfusion associated with acute Type A aortic dissection (ATAAD) in a large, national cohort and the effect of treatment strategy on outcomes.

Methods: All patients undergoing repair of ATAAD between 2017 and 2020 in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database were studied. Malperfusion was defined using STS definitions based on imaging or surgeon's evaluation.

Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism.

Background: Whether to stop oral anticoagulants after a first unprovoked venous thromboembolism (VTE) is challenging, partially due to an intriguingly higher risk of VTE recurrence (rVTE) in men after therapy discontinuation. DNA methylation (DNAm) differences between men and women might underly this sex-biased rVTE risk difference.

Aim: To investigate sex-specific associations between DNAm at cytosine-phosphate-guanine (CpG) sites and rVTE.

Impact of interventions on mpox transmission during the 2022 outbreak in Canada: a mathematical modeling study of three different cities.

Objectives: The global mpox (clade II) outbreak of 2022 primarily affected gay, bisexual, and other men who have sex with men (GBM) and was met with swift community and public health responses. We aimed to estimate the relative impact of changes in sexual behaviours, contact tracing/isolation, and first-dose vaccination on transmission in Canadian cities.

Methods: We estimated changes in sexual behaviours during the outbreak using 2022 data from the Engage Cohort Study which recruited self-identified GBM in Montréal, Toronto, and Vancouver (n=1,445).

Development of a health equity tool in resuscitation sciences and application to current research in extracorporeal cardiopulmonary resuscitation for cardiac arrest.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for adults with cardiac arrest (CA) refractory to Advanced Cardiovascular Life Support (ACLS). Concerns exist that adding ECPR could worsen health inequities, defined as differences in health outcomes that are unfair or unjust. Current guidelines do not explicitly address this issue.

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.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Assessment of radioactivity in soil samples from Wolaita Sodo town, Ethiopia: implications for environmental and public health.

This study assesses the activity concentrations of the radionuclides 238U, 232Th, and 40K in soil samples collected from Wolaita Sodo town, located in the Southern Nations, Nationalities, and Peoples' (SNNP) Region, Ethiopia. A gamma-ray spectrometer equipped with a NaI(Tl) detector was used for the measurements. The concentrations of 238U, 232Th, and 40K varied from 3.

Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results.

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D).

Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.

Associations and potential epigenetic changes between air pollution and osteoarthritis risk and survival: Insights from a prospective cohort study.

Background: The influence of air pollution on osteoarthritis (OA) remains underexplored.

Methods: We conducted a prospective cohort study in the UK Biobank, estimating exposure levels of particulate matter (PM, PM, PM) nitrogen oxides (NO, NO), and air pollutants exposure score (APES). Cox models assessed associations between air pollution exposure and OA incidence, joint replacement, and survival.

Precision Oncology: A Global Perspective on Implementation and Policy Development.

Despite the acknowledged merits of precision oncology (PO) and its increasing global implementation, its full potential for advancing care and prevention remains unrealized. The benefits are currently accessible to only limited patient segments because of multifaceted barriers. Successful implementation hinges on various factors-scientific complexities not limited to technical, clinical, regulatory, economic, administrative, and health care policy-related challenges.

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.

Support for and likely impacts of endgame measures in the Smokefree Aotearoa Action Plan: findings from the 2020-2021 International Tobacco Control New Zealand (EASE) surveys.

Aim: In February 2024, the Aotearoa New Zealand Government repealed legislation to mandate very low nicotine cigarettes (VLNCs), greatly reduce the number of tobacco retailers and disallow sale of tobacco products to people born after 2008 (smokefree generation). We investigated acceptability and likely impacts of these measures among people who smoke or who recently (≤2 years) quit smoking.

Method: We analysed data from 1,230 participants from Wave 3 (conducted in late 2020 and early 2021) and 615 participants from Wave 3.

18F-DCFPyL PET/MRI Radiomics for Intraprostatic Prostate Cancer Detection and Metastases Prediction Using Whole-Gland Segmentation.

Objectives: To evaluate 18F-DCFPyL-PET/MRI whole-gland-derived radiomics for detecting clinically significant (cs) prostate cancer (PCa) and predicting metastasis.

Methods: Therapy-naïve PCa patients who underwent 18F-DCFPyL PET/MRI were included. Whole-prostate-segmentation was performed.

Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52.

G Protein-Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders.

G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers.

Patient Experiences and Perspectives When MyChart is Introduced in a Large Community Hospital: Mixed Methods Study.

Background: Patient portals, or secure websites linked to electronic medical records, have emerged as tools to provide patients with timely access to their health information. To support the potential benefits of patient portals such as improved engagement in health care, it is essential to understand how patients and caregivers experience these portals.

Objective: This study aimed to explore patient and caregiver experiences, facilitators, and barriers to accessing and using a patient portal called MyChart during the initial stages of its implementation.

Governing in the face of a global crisis: When do voters punish and reward incumbent governments?

The recent COVID-19 pandemic offers a rare opportunity to understand how citizens attribute responsibility for governments' responses to unanticipated negative-and in this case, systemic-exogenous shocks. Classical accounts of responsibility are complicated when crises are pervasive, involve multiple valence dimensions, and where individuals can make relative assessments of performance. We fielded a conjoint experiment in 16 countries with 22,147 respondents.

A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer.

Purpose: Understanding real-world treatment patterns and their effectiveness in HR + HER2- advanced breast cancer (aBC) in Canadian patients.

Patient And Methods: This was a multi-center, observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR + HER2- aBC receiving endocrine therapy (ET) or ET + targeted therapy (ET + TT). The primary objective was duration of treatment (DOT) with ET and ET + TT.