Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB.

Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls.

Migration speed of captured breast cancer subpopulations correlates with metastatic fitness.

The genetic alterations contributing to migration proficiency, a phenotypic hallmark of metastatic cells required for colonizing distant organs, remain poorly defined. Here, we used single-cell magneto-optical capture (scMOCa) to isolate fast cells from heterogeneous human breast cancer cell populations, based on their migratory ability alone. We show that captured fast cell subpopulations retain higher migration speed and focal adhesion dynamics over many generations as a result of a motility-related transcriptomic profile.

Nutritional Aspects of Iron in Health and Disease.

Dietary iron assimilation is critical for health and essential to prevent iron-deficient states and related comorbidities, such as anemia. The bioavailability of iron is generally low, while its absorption and metabolism are tightly controlled to satisfy metabolic needs and prevent toxicity of excessive iron accumulation. Iron entry into the bloodstream is limited by hepcidin, the iron regulatory hormone.

External validation of the ISARIC 4C Mortality Score to predict in-hospital mortality among patients with COVID-19 in a Canadian intensive care unit: a single-centre historical cohort study.

Purpose: With uncertain prognostic utility of existing predictive scoring systems for COVID-19-related illness, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) 4C Mortality Score was developed by the International Severe Acute Respiratory and Emerging Infection Consortium as a COVID-19 mortality prediction tool. We sought to externally validate this score among critically ill patients admitted to an intensive care unit (ICU) with COVID-19 and compare its discrimination characteristics to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores.

Methods: We enrolled all consecutive patients admitted with COVID-19-associated respiratory failure between 5 March 2020 and 5 March 2022 to our university-affiliated and intensivist-staffed ICU (Jewish General Hospital, Montreal, QC, Canada).

Novel insights into systemic sclerosis using a sensitive computational method to analyze whole-genome bisulfite sequencing data.

Background: Abnormal DNA methylation is thought to contribute to the onset and progression of systemic sclerosis. Currently, the most comprehensive assay for profiling DNA methylation is whole-genome bisulfite sequencing (WGBS), but its precision depends on read depth and it may be subject to sequencing errors. SOMNiBUS, a method for regional analysis, attempts to overcome some of these limitations.

B cell-specific knockout of AID protects against atherosclerosis.

Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance.

Perceptions and Usability of PREVENTION: A Breast Cancer Risk Assessment e-Platform.

Background: The PREVENTION e-platform was developed to provide accessible and evidence-based health information tailored to different Breast Cancer (BC) risk levels. The demonstration study objectives were to (1) assess the usability and perceived impact of PREVENTION on women with assigned hypothetical BC risk levels (i.e.

Development of an evidence-based educational resource in oncology: 'Living safely with bone metastases'.

Objective: To create an evidence-based patient education resource to better support cancer patients with bone metastases in carrying out safe movements during activities of daily living, to maintain their bone health and reduce the risk of fractures.

Methods: A quality improvement project was conducted in three phases: Development of the Resource, Preliminary Feedback and Revision, and French Canadian Translation.

Results: The educational resource focuses on safe movement, activities of daily living, and exercise, organized within the sections , and .

The Utility of Urodynamic Studies in Neuro-Urological Patients.

Introduction: The utility of a clinical tool lies in its clinical performance evaluation and describes the relevance and usefulness of that tool in a medical setting. The utility of urodynamic and video-urodynamic studies in the management of specific urodynamic profiles in the diagnosis, treatment, and prognostic approach in neuro-urological patients is the focus of the current review.

Methods: For this narrative review, a PubMed search was performed by cross-referencing the keywords "urodynamics", "neurogenic bladder", "utility", "clinical utility" and "clinical performance" with various terms related to the management of neurogenic lower urinary tract dysfunction.

Evidence-Based Practice in Psychosocial Oncology from the Perspective of Canadian Service Directors.

Evidence-based practices facilitate the effective delivery of psychological services, yet research on the implementation of evidence-based practices in psychosocial oncology (PSO) is scarce. Responding to this gap, we interviewed a diverse sample of 16 directors of Canadian psychosocial oncology services about (a) how evidence-based practices in psychosocial oncology are being implemented in clinical care and how the service quality is monitored and (b) what are barriers and facilitators to evidence-based practice in psychosocial oncology services? Responses were grouped according to three main themes emerging from the data: screening for distress and referral to PSO services, delivery of evidence-based PSO services, and monitoring of PSO services. Our findings highlight facilitators and barriers to evidence-based practice in psychosocial oncology, which were related to the political, social, economic, and geographic contexts.

Consensus Recommendations to Optimize the Detection and Reporting of Gene Fusions by RNA-Based Next-Generation Sequencing.

The detection of gene fusions by RNA-based next-generation sequencing (NGS) is an emerging method in clinical genetic laboratories for oncology biomarker testing to direct targeted therapy selections. A recent Canadian study (CANTRK study) comparing the detection of gene fusions on different NGS assays to determine subjects' eligibility for tyrosine kinase TRK inhibitor therapy identified the need for recommendations for best practices for laboratory testing to optimize RNA-based NGS gene fusion detection. To develop consensus recommendations, representatives from 17 Canadian genetic laboratories participated in working group discussions and the completion of survey questions about RNA-based NGS.

The Role of the Estrogen-Related Receptor Alpha (ERRa) in Hypoxia and Its Implications for Cancer Metabolism.

Under low oxygen conditions (hypoxia), cells activate survival mechanisms including metabolic changes and angiogenesis, which are regulated by HIF-1. The estrogen-related receptor alpha (ERRα) is a transcription factor with important roles in the regulation of cellular metabolism that is overexpressed in hypoxia, suggesting that it plays a role in cell survival in this condition. This review enumerates and analyses the recent evidence that points to the role of ERRα as a regulator of hypoxic genes, both in cooperation with HIF-1 and through HIF-1- independent mechanisms, in invertebrate and vertebrate models and in physiological and pathological scenarios.

Paper II: thematic framework analysis of registry-based randomized controlled trials provided insights for designing trial ready registries.

Objectives: Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional randomized controlled trials. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs.

Study Design And Setting: We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n = 12), followed by an analysis of RRCT protocols (n = 13) and reports (n = 77) identified from a scoping review.

SARS-CoV-2 ORF8: A Rapidly Evolving Immune and Viral Modulator in COVID-19.

The COVID-19 pandemic has resulted in upwards of 6.8 million deaths over the past three years, and the frequent emergence of variants continues to strain global health. Although vaccines have greatly helped mitigate disease severity, SARS-CoV-2 is likely to remain endemic, making it critical to understand its viral mechanisms contributing to pathogenesis and discover new antiviral therapeutics.

Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle.

A rapidly evolving understanding of phase separation in the biological and physical sciences has led to the redefining of virus-engineered replication compartments in many viruses with RNA genomes. Condensation of viral, host and genomic and subgenomic RNAs can take place to evade the innate immunity response and to help viral replication. Divergent viruses prompt liquid-liquid phase separation (LLPS) to invade the host cell.

Health Care Utilization: What Is the Cost of Caring for Scleroderma?

Systemic sclerosis (SSc), also known as scleroderma, is a chronic autoimmune connective tissue disease and is associated with a significant economic burden resulting from health care utilization costs in addition to indirect costs attributable to SSc resulting from early retirement and lost productivity in those that remain in employment.

Predicting ExWAS findings from GWAS data: a shorter path to causal genes.

GWAS has identified thousands of loci associated with disease, yet the causal genes within these loci remain largely unknown. Identifying these causal genes would enable deeper understanding of the disease and assist in genetics-based drug development. Exome-wide association studies (ExWAS) are more expensive but can pinpoint causal genes offering high-yield drug targets, yet suffer from a high false-negative rate.