Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022).

Health recommender systems to facilitate collaborative decision-making in chronic disease management: A scoping review.

Objective: Health recommender systems (HRSs) are increasingly used to complement existing clinical decision-making processes, but their use for chronic diseases remains underexplored. Recognizing the importance of collaborative decision making (CDM) and patient engagement in chronic disease treatment, this review explored how HRSs support patients in managing their illness.

Methods: A scoping review was conducted using the framework proposed by Arksey and O'Malley, advanced by Levac et al.

Statistical Testing of Random Number Generators and Their Improvement Using Randomness Extraction.

Random number generators (RNGs) are notoriously challenging to build and test, especially for cryptographic applications. While statistical tests cannot definitively guarantee an RNG's output quality, they are a powerful verification tool and the only universally applicable testing method. In this work, we design, implement, and present various post-processing methods, using randomness extractors, to improve the RNG output quality and compare them through statistical testing.

Women's perspectives to improve prenatal care for gestational diabetes: A systematic review and meta-aggregation of qualitative studies.

Introduction: In numerous qualitative primary studies, women have identified opportunities to improve prenatal gestational diabetes care. The objective of our systematic review and meta-aggregation was to synthesize patient-guided suggestions for improving prenatal gestational diabetes care that are informed by lived experience of women and their support persons.

Material And Methods: This study was registered a priori on PROSPERO (CRD42023394014).

Evaluating Renal Disease in Pediatric-Onset Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Disease Course, Outcomes, and Predictors of Outcome.

Objective: We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys.

Methods: Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or ANCA-positive pauci-immune glomerulonephritis, were 18 years or younger at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and at either 12 or 24 months. Ambispective data from A Registry for Children with Vasculitis/Pediatric Vasculitis Initiative Registry was used.

The effectiveness of continuous glucose monitoring with remote telemonitoring-enabled virtual educator visits in adults with non-insulin dependent type 2 diabetes: A randomized trial.

Aims: Estimate the effectiveness of continuous glucose monitoring (CGM) with remote telemonitoring-enabled virtual diabetes educator visits for improving glycemic management in adults with type 2 diabetes, not on insulin.

Methods: Participants with type 2 diabetes, not on insulin, and HbA1c > 7.0 % were enrolled in an open-label randomized trial of 6 weeks of CGM with telemonitoring versus enhanced usual care.

LiverMap pipeline for 3D imaging of human liver reveals volumetric spatial dysregulation of cirrhotic vasculobiliary architecture.

The liver contains an intricate microstructure that is critical for liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, 2D histopathology - the gold standard for pathological understanding of many liver diseases - can misrepresent or leave gaps in our understanding of complex 3D structural features.

Use of Sodium-Glucose Cotransporter-2 Inhibitors in Adults Aged ≥65 Years With Type 2 Diabetes and Cardiovascular Disease: A Cross-sectional Study of Different Drug Funding Policies.

Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide heart and kidney benefits in adults with diabetes and cardiovascular disease (CVD). Public drug coverage policies for SGLT2is differ by province in Canada. In this study, we describe the potential effects of prior authorization/step therapy (PA/ST) and relatively high income-based deductibles, compared with regular benefit status with modest copay, on SGLT2i prescriptions in high-risk adults.

Label-free, real-time monitoring of cytochrome C drug responses in microdissected tumor biopsies with a multi-well aptasensor platform.

Functional assays on intact tumor biopsies can complement genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key therapeutic response determinants, such as tissue architecture, tumor heterogeneity, and the tumor microenvironment. Most of these assays rely on fluorescent labeling, a semiquantitative method best suited for single-time-point assays or labor-intensive immunostaining analysis. Here, we report integrated aptamer electrochemical sensors for on-chip, real-time monitoring of cytochrome C, a cell death indicator, from intact microdissected tissues with high affinity and specificity.

Validation of the EQ-5D-Y-5L parent-proxy version among children with juvenile idiopathic arthritis.

Objectives: Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children. It can cause joint pain and permanent physical damage, which affects mobility and daily activities. The EQ-5D-Y-3L self-report version has been validated in JIA, but the validity of EQ-5D-Y-5L remains unknown.

Kawasaki Disease-Associated Cytokine Storm Syndrome.

Kawasaki disease (KD) is a hyperinflammatory syndrome manifesting as an acute systemic vasculitis characterized by fever, nonsuppurative conjunctival injection, rash, oral mucositis, extremity changes, and cervical lymphadenopathy. KD predominantly affects young children and shares clinical features and immunobiology with other hyperinflammation syndromes including systemic juvenile idiopathic arthritis (sJIA) and multisystem inflammatory syndrome in children (MIS-C). Cytokine storm syndrome (CSS) is an acute complication in ~2% of KD patients; however, the incidence is likely underestimated as many clinical and laboratory features of both diseases overlap.

Interleukin-1-mediated hyperinflammation in XIAP deficiency is associated with defective autophagy.

Deficiency of X-linked inhibitor of apoptosis protein (XIAP) is a rare genetic condition that can present with recurrent episodes of hemophagocytic lymphohistiocytosis (HLH), though the exact mechanisms leading to this hyperinflammatory disorder are unclear. Understanding its biology is critical to developing targeted therapies for this potentially fatal disease. Here, we report on a novel multiexonic intragenic duplication leading to XIAP deficiency with recurrent HLH that demonstrated complete response to interleukin (IL)-1β blockade.

Enabling extracorporeal ultrasound imaging with the da Vinci robot for transoral robotic surgery: a feasibility study.

Purpose: Transoral robotic surgery (TORS) is a challenging procedure due to its small workspace and complex anatomy. Ultrasound (US) image guidance has the potential to improve surgical outcomes, but an appropriate method for US probe manipulation has not been defined. This study evaluates using an additional robotic (4th) arm on the da Vinci Surgical System to perform extracorporeal US scanning for image guidance in TORS.

SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive bile duct malignancy that frequently exhibits isocitrate dehydrogenase () mutations. Mutant IDH (IDHm) ICC is dependent on SRC kinase for growth and survival and is hypersensitive to inhibition by dasatinib, but the molecular mechanism underlying this sensitivity is unclear. We found that dasatinib reduced p70 S6 kinase (S6K) and ribosomal protein S6 (S6), leading to substantial reductions in cell size and de novo protein synthesis.

Recurrent involuntary memories and mind wandering are related but distinct.

Spontaneous thought is common in daily life, and includes recurrent involuntary autobiographical memories (IAMs; memories retrieved unintentionally and repetitively) and mind wandering (MW). Both recurrent IAMs and MW are often unintentional or unconstrained, and both predict symptoms of mental health disorders. However, not all MW is unintentional, and not all IAMs are unconstrained.

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

Background: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline.

Methods And Results: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period.

Specific topics, specific symptoms: linking the content of recurrent involuntary memories to mental health using computational text analysis.

Researchers debate whether recurrent involuntary autobiographical memories (IAMs; memories of one's personal past retrieved unintentionally and repetitively) are pathological or ordinary. While some argue that these memories contribute to clinical disorders, recurrent IAMs are also common in everyday life. Here, we examined how the content of recurrent IAMs might distinguish between those that are maladaptive (related to worse mental health) versus benign (unrelated to mental health).

Low-Cost Robotic Manipulation of Live Microtissues for Cancer Drug Testing.

Unlabelled: The scarcity of human biopsies available for drug testing is a paramount challenge for developing new therapeutics, disease models, and personalized treatments. Microtechnologies that combine the microscale manipulation of tissues and fluids offer the exciting possibility of miniaturizing both disease models and drug testing workflows on scarce human biopsies. Unfortunately, these technologies presently require microfluidic devices or robotic dispensers that are not widely accessible.

Microdissected tumor cuboids: a microscale cancer model for large-scale testing that retains a complex tumor microenvironment.

To bridge the gap between bench and bedside, there is a need for more faithful models of human cancers that can recapitulate key features of the human tumor microenvironment (TME) and simultaneously facilitate large-scale drug tests. Our recently developed microdissection method optimizes the yield of large numbers of cuboidal microtissues (″cuboids″, ~(400 µm) ) from a tumor biopsy. Here we demonstrate that cuboids from syngeneic mouse tumor models and human tumors retain a complex TME, making them amenable for drug and immunotherapy evaluation.

Real-world Use and Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada.

Objectives: Since 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure.

Methods: This retrospective, population-based cohort study identified people with diabetes and heart failure between January 1, 2014, and December 31, 2017, in Alberta, Canada, and followed them for a minimum of 3 years for SGLT2i dispensation and outcomes.

Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.

Objective: To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH) genes and systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).

Methods: Targeted sequencing of HLH genes (, , , , , ) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtained (dbGaP:phs000280.

Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade.

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL).