Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Characterization of senescence-associated transcripts in the human placenta.

Introduction: Fusion of mononucleated cytotrophoblasts into syncytium leads to trophoblast senescence. Yet, premature senescence is associated with preeclampsia, fetal growth restriction (FGR), and related obstetrical syndromes. A set of 28 transcripts that comprise senescence-associated secretory phenotype (SASP) was recently described in placentas from women with preeclampsia.

Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade.

Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout.

Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations.

Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo.

Working effectively with individuals with substance use disorders: a qualitative descriptive study.

Background: Irrespective of where nurses work, they may provide care to individuals with substance use disorders. Unfortunately, some nurses may not understand how to work with these individuals and stigmatisation may occur.

Aim: To explore how to provide effective care for these individuals.

Health-Related Quality of Life Among Patients Who Have Survived an Episode of Sepsis in the United States: A Systematic Review.

Introduction: Sepsis is a serious condition that may lead to death or profoundly affect the well-being of those who survive. The aim of this systematic review was to identify and summarize evidence on the impact of all-cause sepsis on health-related quality of life (HRQoL), physical, cognitive, and psychological outcomes among sepsis survivors in the USA.

Methods: Studies assessing HRQoL, physical, cognitive, and psychological outcomes in patients who survived an episode of sepsis and published from January 1, 2010, to September 30, 2023, were systematically identified through EMBASE, MEDLINE, and MEDLINE In-Process databases, as well as through gray literature.

Extreme heat risk and the potential implications for the scheduling of football matches at the 2026 FIFA World Cup.

Climate change is making extreme heat events more frequent and intense. This negatively impacts many aspects of society, including organised sport. As the world's most watched sporting event, the FIFA World Cup commands particular attention around the threat of extreme heat.

Interest in digital health tools for miscarriage support: A qualitative assessment of Canadian women facing early pregnancy loss.

Background: Early pregnancy loss (EPL) occurs in 10%-15% of all pregnancies but remains an underrecognized and undertreated condition. In Canada, resources to support individuals and their partners facing EPL remain scarce despite a high burden of psychosocial sequelae. Digital health tools hold the potential to fill important gaps in reproductive healthcare.

Task activation results in regional C-lactate signal increase in the human brain.

Hyperpolarized-C magnetic resonance imaging (HP-C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

Congenital cardiac surgical simulation: bridging global workforce gaps and optimizing outcomes.

Reaching competency in congenital heart surgery (CHS) requires lengthy and rigorous training. Due to patient safety, time limitations, and procedural complexity, the intraoperative setting is not ideal for technical practice. Surgical simulation using synthetic, biological, or virtual models is an increasingly valuable educational tool for technical training and assessment.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

From Federal Policy to Bedside Care: A Canadian Perspective on Key Considerations for Nurse Executive Action for AI Adoption - A Commentary.

The integration of artificial intelligence (AI) into healthcare represents a paradigm shift with the potential to enhance patient care and streamline clinical operations. This commentary explores the Canadian perspective on key organizational considerations for nurse executives, emphasizing the critical role they play in fostering the establishment of AI governance structures and advancing the front-line adoption of AI in nursing practice. The discussion delves into five domains of consideration, analyzing recent developments and implications for nursing executives.

How Whiteness Shapes Nursing in Canada - What Does the Literature Say? A Rapid Review.

Globally and nationally, there has been growing understanding and acknowledgment of systemic racism and its impact as a structural determinant of health. The profession of nursing has an obligation to carefully self-examine so it does not further contribute to systemic racism. Using the National Collaborating Centre for Methods and Tools' rapid review methodology, this rapid review of the literature seeks to understand how whiteness shapes the Canadian nursing profession.

Sexual Orientation Disclosure and Strategic Navigation of Interpersonal Invisibility.

People with concealable stigmatized identities may strategically share or hide cues to their identity. They may likewise seek or avoid interpersonal invisibility (i.e.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

Exploiting the Achilles' Heel of Viral RNA Processing to Develop Novel Antivirals.

Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.

A Review of Food-Related Social Media and Its Relationship to Body Image and Disordered Eating.

Background/objectives: Appearance-related social media, such as "thinspiration" and "fitspiration" posts, have been shown to contribute to poor body image and disordered eating. Food-related social media is becoming increasingly popular; however, far less is known about its relationship to body image and disordered eating.

Methods: The current review searched PsycNet and PubMed (Medline) for all the literature examining food-related social media and its relationship with body image and/or disordered eating outcomes.

Prediction Model for POstoperative atriaL fibrillAtion in caRdIac Surgery: The POLARIS Score.

: New-onset postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, occurring approximately in one-third of the patients. This study considered all-comer patients who underwent cardiac surgery to build a predictive model for POAF. : A total of 3467 (Center 1) consecutive patients were used as a derivation cohort to build the model.

Assessing the Impact of the Prone Position on Acute Kidney Injury.

: Prone positioning is a standard intervention in managing patients with severe acute respiratory distress syndrome (ARDS) and is known to improve oxygenation. However, its effects on other organs, particularly the kidneys, are less well understood. This study aimed to assess the association between prone positioning and the development of acute kidney injury (AKI), specifically in overweight and obese patients.

Periocular Aging Across Populations and Esthetic Considerations: A Narrative Review.

As the face ages, the skin, fat, muscle, and fascia descend, and the underlying bone, cartilage, and teeth may lose mass. Oculofacial aging is a multifactorial process that is influenced by genetic, environmental, and lifestyle factors. This review summarizes the patterns of oculofacial aging that are observed across populations, including variations in periorbital hollowing, eyelid ptosis, and skin elasticity.

Donor Lungs' Procurement Implementation with Ex Vivo Lung Perfusion in a Low-Volume Lung Transplant Center.

(1) Background: Ex Vivo Lung Perfusion (EVLP) is a technique designed to assess and recondition marginal lungs, potentially expanding the donor pool and improving transplant outcomes (2) Methods: This retrospective study evaluated lung transplantation outcomes after EVLP. Donor lungs were assessed using the Toronto protocol, with data on hemodynamics, gas exchange, and perfusion parameters collected and analyzed. Post-transplant complications and survival rates were also examined.

HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity.

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein.