repeat expansion creates the unstable folate-sensitive fragile site FRA9A.

The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and , is linked to multiple diseases. (GGGGCC)n expansions (Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immunostimulatory or damaged DNA is unknown.

Impacts of the COVID-19 pandemic on access to sexual and reproductive health services for women and gender-diverse people with disabilities in Canada: a qualitative study.

The COVID-19 pandemic has had a detrimental impact on sexual and reproductive health (SRH) and rights globally. However, little is known about the experiences of people with disabilities accessing SRH services during the COVID-19 pandemic. In this community-engaged qualitative study, we examined COVID-related impacts on access to SRH services for people with disabilities.

Clinical Utility of Genomic Sequencing for Hereditary Cancer Syndromes: An Observational Cohort Study.

Purpose: Genomic sequencing (GS) is increasingly used to improve diagnoses and inform targeted therapies. GS can also be used to identify the 10% of cancer patients with an underlying hereditary cancer syndrome (HCS), who can benefit from surveillance and preventive surgery that reduce morbidity/mortality. However, the evidence on clinical utility of GS for HCS is limited: we aimed to fill this gap by assessing yield of all cancer results and associated recommendations for patients undergoing GS for HCS.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

Mortality Among Severely Injured Adolescents Admitted to Pediatric vs Adult Trauma Centers.

Importance: Care in a pediatric (vs adult) trauma center improves outcomes for injured children aged 0 to 12 years, but whether pediatric care benefits injured adolescents is unclear.

Objective: To evaluate the association of pediatric vs adult trauma center care with mortality among severely injured adolescents.

Design, Setting, And Participants: This retrospective cohort study was conducted between April 1, 2012, and March 31, 2020, among adolescents aged 12 to 16 years who were admitted to level I or level II adult trauma centers or a level I pediatric trauma center in British Columbia, Canada.

Face Masking and Risk of Post-Intravitreal Injection Endophthalmitis: A Network Meta-Analysis of 2.6 Million Injections.

Topic: To compare face masking protocols for post-intravitreal injection endophthalmitis (PIE) prophylaxis.

Clinical Relevance: Though mask mandates are lifted, ophthalmologists may question whether continued investment into face masks will influence their PIE rate.

Methods/literature Reviewed: We included comparative studies of PIE incidence by masking policy (i.

The legacy of the COVID-19 pandemic on critical care research: A descriptive interview study.

Background: The COVID-19 pandemic challenged both research and clinical teams in critical care to collaborate on research solutions to new clinical problems. Although an effective, nationally coordinated response helped facilitate critical care research, reprioritisation of research efforts towards COVID-19 studies had significant consequences for existing and planned research activity in critical care.

Aims: Our aim was to explore the impact of the COVID-19 pandemic research prioritisation policies and practices on critical care research funded prior to the pandemic, the conduct of pandemic research, and implications for ongoing and future critical care research.

Equity Landscape in Healthcare Quality: A Mixed-Methods Study of Efforts within Surgical Quality Programs.

Background: Addressing equity in healthcare is necessary to improve population health outcomes. In doing so, a requisite level of foundational resources, organization, and processes are needed. Although increasing attention is being devoted to addressing health inequities, the current landscape supporting these efforts remains unknown.

Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.

Background: The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.

Methods: We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 12 months.

Social Determinants of Health in Age-Related Macular Degeneration: A Nationally Representative Survey Study.

Purpose: To investigate the relationship between social determinants of health (SDoH) and the prevalence of age-related macular degeneration (AMD).

Methods: This analysis included adult respondents (>50 years old) from the 2017 National Health Interview Survey (NHIS). The primary outcomes were self-reported diagnosis of AMD and self-reported vision loss due to AMD.

Perceptions of physical activity among individuals with limb loss: A qualitative study.

Objectives: Individuals with lower-limb amputations (LLA) often have deficits in balance and community walking ability. As a result, people with LLA are often sedentary. The aim of this study was to explore perceptions of physical activity from the perspective of people with LLA.

Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial.

Background: There is heterogeneity of aerobic fitness (VO) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO).

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Cisplatin- or Carboplatin-Based Chemotherapy Plus Pembrolizumab in Advanced Urothelial Cancer: Exploratory Analysis From the Phase 3 KEYNOTE-361 Study.

Introduction: KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary end points of progression-free survival (PFS) or overall survival (OS) were not met. Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.

Impact of Clinical Trial Enrollment on Thrombolysis Workflow in a Mobile Stroke Unit: Results from the AcT Trial.

Background: The Edmonton-based mobile stroke unit (MSU), which transports patients to the University of Alberta Hospital (UAH), enrolled patients in the Intravenous Tenecteplase Compared with Alteplase for Acute Ischemic Stroke (AcT) trial. We examined the feasibility of trial enrollment in MSU, its impact on acute stroke workflow metrics and functional outcomes at 90-120 days.

Methods: In this post hoc analysis, patients were divided into three groups based on enrollment site: MSU ( = 43), UAH ( = 273) and non-UAH ( = 1261).

Intersection of Performance, Interpretability, and Fairness in Neural Prototype Tree for Chest X-Ray Pathology Detection: Algorithm Development and Validation Study.

Background: While deep learning classifiers have shown remarkable results in detecting chest X-ray (CXR) pathologies, their adoption in clinical settings is often hampered by the lack of transparency. To bridge this gap, this study introduces the neural prototype tree (NPT), an interpretable image classifier that combines the diagnostic capability of deep learning models and the interpretability of the decision tree for CXR pathology detection.

Objective: This study aimed to investigate the utility of the NPT classifier in 3 dimensions, including performance, interpretability, and fairness, and subsequently examined the complex interaction between these dimensions.