Hematologic characteristics and coagulopathy in pregnancy with COVID-19 succeeding the first wave: a multicenter retrospective cross-sectional study.

Background: Early reports have demonstrated an association of COVID-19 infection during pregnancy and postpartum period with coagulopathy and bleeding complications and indicated that pregnant people with COVID-19 are more likely to experience coagulopathy and venous thromboembolism. A recent report concerning such complications during the first wave of the pandemic was reassuring; however, no publications have evaluated these issues in the context of increased illness severity with the emergence of SARS-CoV-2 variants of concern.

Objectives: We performed a retrospective, multinational cohort study in Canada, Romania, and the United Kingdom, aiming to provide a comprehensive analysis of the hematologic test characteristics of pregnancies affected by COVID-19 after the first wave of the pandemic.

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC.

Purpose: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines.

Experimental Design: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers.

Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation.

Background: Bioengineered cartilage is a developing therapeutic to repair cartilage defects. The matrix must be rich in collagen type II and aggrecan and mechanically competent, withstanding compressive and shearing loads. Biomechanical properties in native articular cartilage depend on the zonal architecture consisting of 3 zones: superficial, middle, and deep.

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.

Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder associated with traumatic memory, yet its etiology remains unclear. Reexperiencing symptoms are specific to PTSD compared to other anxiety-related disorders. Importantly, reexperiencing can be mimicked by retrieval-related events of fear memory in animal models of traumatic memory.

Cellular transfection using rapid decrease in hydrostatic pressure.

Of all methods exercised in modern molecular biology, modification of cellular properties through the introduction or removal of nucleic acids is one of the most fundamental. As such, several methods have arisen to promote this process; these include the condensation of nucleic acids with calcium, polyethylenimine or modified lipids, electroporation, viral production, biolistics, and microinjection. An ideal transfection method would be (1) low cost, (2) exhibit high levels of biological safety, (3) offer improved efficacy over existing methods, (4) lack requirements for ongoing consumables, (5) work efficiently at any scale, (6) work efficiently on cells that are difficult to transfect by other methods, and (7) be capable of utilizing the widest array of existing genetic resources to facilitate its utility in research, biotechnical and clinical settings.

The CNK-HYP scaffolding complex promotes RAF activation by enhancing KSR-MEK interaction.

The RAS-MAPK pathway regulates cell proliferation, differentiation and survival, and its dysregulation is associated with cancer development. The pathway minimally comprises the small GTPase RAS and the kinases RAF, MEK and ERK. Activation of RAF by RAS is notoriously intricate and remains only partially understood.

Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists.

Objective: To assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension.

Methods: Cross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada.

Results: The overall response rate was 33% (72/206), with a completion rate was 94%.

Integrating single-cell and spatially resolved transcriptomic strategies to survey the astrocyte response to stroke in male mice.

Astrocytes, a type of glial cell in the central nervous system (CNS), adopt diverse states in response to injury that are influenced by their location relative to the insult. Here, we describe a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics). We use tDISCO alongside two high-throughput platforms for spatial (Visium) and single-cell transcriptomics (10X Chromium) to examine the heterogeneity of the astrocyte response to a cortical ischemic stroke in male mice.

The ILC Maine statement: Time for the fundamental care [r]evolution.

Aim: The aim of this study was to present the third position statement from the International Learning Collaborative (ILC). The ILC is the foremost global organization dedicated to transforming fundamental care. Internationally, fundamental care is reported to be poorly delivered, delayed or missed, negatively impacting patients, their families/carers and healthcare staff and systems.

Co-design for stroke intervention development: Results of a scoping review.

Background: Co-design methodology seeks to actively engage end-users in developing interventions. It is increasingly used to design stroke interventions; however, limited guidance exists, particularly with/for individuals with stroke who have diverse cognitive, physical and functional abilities. Thus, we describe 1) the extent of existing research that has used co-design for stroke intervention development and 2) how co-design has been used to develop stroke interventions among studies that explicitly used co-design, including the rationale, types of co-designed stroke interventions, participants involved, research methodologies/approaches, methods of incorporating end-users in the research, co-design limitations, challenges and potential strategies reported by researchers.

Lipid profile of circulating placental extracellular vesicles during pregnancy identifies foetal growth restriction risk.

Small-for-gestational age (SGA) neonates exhibit increased perinatal morbidity and mortality, and a greater risk of developing chronic diseases in adulthood. Currently, no effective maternal blood-based screening methods for determining SGA risk are available. We used a high-resolution MS/MS shotgun lipidomic approach to explore the lipid profiles of small extracellular vesicles (sEV) released from the placenta into the circulation of pregnant individuals.

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Context: Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined.

Objective: Our objective was to assess the association of uVDBP with longitudinal changes in kidney function.

Methods: Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727).

Diagnostic and progression biomarkers in cerebrospinal fluid of Alzheimer's disease patients.

In this commentary, we address a paper published by Johnson et al. by assessing the robustness of their method to discover diagnostic biomarkers in Alzheimer's disease (AD). In addition, we examine how these newly discovered and previously discovered biomarkers, can play a role in assisting patients with AD and those at risk for developing AD, with an emphasis on the translational hurdles that accompany such discoveries.

β-catenin mediates growth defects induced by centrosome loss in a subset of APC mutant colorectal cancer independently of p53.

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths worldwide. The centrosome is the main microtubule-organizing center in animal cells and centrosome amplification is a hallmark of cancer cells. To investigate the importance of centrosomes in colorectal cancer, we induced centrosome loss in normal and cancer human-derived colorectal organoids using centrinone B, a Polo-like kinase 4 (Plk4) inhibitor.

A Web-Based Peer-Patient Navigation Program (Compassionate Online Navigation to Enhance Care Transitions) for Youth Living With Childhood-Acquired Disabilities Transitioning From Pediatric to Adult Care: Qualitative Descriptive Study.

Background: Studies have highlighted significant challenges associated with the transition from pediatric to adult health and social care services for youth living with childhood-acquired disabilities and their caregivers. Patient navigation has been proposed as an effective transitional care intervention. Better understanding of how patient navigation may support youth and their families during pediatric to adult care transitions is warranted.

How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.

Introduction: Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear.

Methods: We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimated glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy or death due to kidney disease) in EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

Background: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

Methods: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.

Mapping Theories, Models, and Frameworks to Evaluate Digital Health Interventions: Scoping Review.

Background: Digital health interventions (DHIs) are a central focus of health care transformation efforts, yet their uptake in practice continues to fall short of their potential. In order to achieve their desired outcomes and impact, DHIs need to reach their target population and need to be used. Many factors can rapidly intersect between this dynamic of users and interventions.