Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study Design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.

Bridging the Gap: Comparing Patient-Clinician Views on Treatment Goals and Communication in the Management of Atopic Dermatitis Within the Asia-Pacific Region.

Introduction: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia.

Methods: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

Background: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres.

Prognostic Value of Microvascular Resistance Reserve Measured Immediately After PCI in Stable Coronary Artery Disease.

Background: Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Background: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.

The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

Background And Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance.

Helicobacter pylori Seropositivity, ABO Blood Type, and Pancreatic Cancer Risk From 5 Prospective Cohorts.

Background: Helicobacter pylori infection may be a risk factor for pancreatic cancer, particularly infection by strains without the cytotoxin-associated gene A (CagA) virulence factor. Non-O blood type is a known risk factor for pancreatic cancer, and H. pylori gastric colonization occurs largely from bacterial adhesins binding to blood group antigens on gastric mucosa.

CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma.

Deregulation of cell cycle is a typical feature of cancer cells. Normal cells rely on the strictly coordinated spindle assembly checkpoint (SAC) to maintain the genome integrity and survive. However, cancer cells could bypass this checkpoint mechanism.

Development, implementation and initial feasibility testing of the MediEmo mobile application to provide support during medically assisted reproduction.

Study Question: Is it possible to develop a patient smartphone application for medically assisted reproduction (MAR) that is acceptable to patients and fertility staff?

Summary Answer: Staff and patients responded positively to the MediEmo smartphone application, perceiving it to be acceptable and feasible to implement in a busy clinic.

What Is Known Already: Digital tools are increasingly popular to provide practical, administrative and psychological support alongside medical treatments. Apps and other digital tools have been developed for use alongside MAR but there is very limited research on the development or acceptability and feasibility of these tools.

A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention.

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

Characterization of Psychotropic PRN Medications in a Canadian Psychiatric Intensive Care Unit.

Background: Pro re nata (PRN) antipsychotics and benzodiazepines are routinely used for the rapid stabilization of acutely agitated patients. Despite the popular use of PRN medications in mental health units, primary literature supporting efficacy and safety is poor, and there is no single universally accepted practice guideline. PRN psychotropic medications have the potential to cause adverse effects when used inappropriately.

Challenges for Family Medicine Residents in Attaining the CanMEDS Professional Role: A Thematic Analysis of Preceptor Field Notes.

Purpose: Among the roles of the competent physician is that of a professional, according to the Canadian Medical Education Directives for Specialists (CanMEDS) framework, which describes the abilities physicians require to effectively meet the health care needs of the people they serve. Through examination of preceptor field notes on resident performance, the authors identified aspects of this role with which family medicine residents struggle.

Method: The authors used a structured thematic analysis in this qualitative study to explore the written feedback postgraduate medical learners receive at the University of Toronto Department of Family and Community Medicine.

Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus.