Increasing and maintaining rates of standardized depression screening in youth with childhood-onset systemic lupus erythematosus in a pediatric rheumatology clinic.

Background: Depression adversely affects health outcomes in patients with childhood-onset systemic lupus erythematous (cSLE). By identifying patients with depressive symptoms, we can intervene early with referrals to mental health resources and improve outcomes. The aim of our quality improvement project was to increase and maintain rates of standardized depression screening for youth with cSLE seen within our pediatric rheumatology clinic.

Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.

Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).

Using induced pluripotent stem cells for drug discovery in arrhythmias.

Introduction: Arrhythmias are disturbances in the normal rhythm of the heart and account for significant cardiovascular morbidity and mortality worldwide. Historically, preclinical research has been anchored in animal models, though physiological differences between these models and humans have limited their clinical translation. The discovery of human induced pluripotent stem cells (iPSC) and subsequent differentiation into cardiomyocyte has led to the development of new models of arrhythmias with the hope of a new pathway for both exploration of pathogenic variants and novel therapeutic discovery.

BeatProfiler: Multimodal In Vitro Analysis of Cardiac Function Enables Machine Learning Classification of Diseases and Drugs.

Contractile response and calcium handling are central to understanding cardiac function and physiology, yet existing methods of analysis to quantify these metrics are often time-consuming, prone to mistakes, or require specialized equipment/license. We developed BeatProfiler, a suite of cardiac analysis tools designed to quantify contractile function, calcium handling, and force generation for multiple in vitro cardiac models and apply downstream machine learning methods for deep phenotyping and classification. We first validate BeatProfiler's accuracy, robustness, and speed by benchmarking against existing tools with a fixed dataset.

The Subgroup Imperative: Chest Radiograph Classifier Generalization Gaps in Patient, Setting, and Pathology Subgroups.

Purpose: To externally test four chest radiograph classifiers on a large, diverse, real-world dataset with robust subgroup analysis.

Materials And Methods: In this retrospective study, adult posteroanterior chest radiographs (January 2016-December 2020) and associated radiology reports from Trillium Health Partners in Ontario, Canada, were extracted and de-identified. An open-source natural language processing tool was locally validated and used to generate ground truth labels for the 197 540-image dataset based on the associated radiology report.

Immersive Cooling in the Prehospital Setting for Heat Stroke: A Case Report.

Non-exertional heat stroke is defined as exposure to high outdoor temperatures, core body temperature >40 °C, and alteration of mentation. Early identification and treatment are imperative to reduce morbidity and mortality in these patients. Cold water immersion therapy is the most efficient and efficacious modality in treating heat stroke, yet it is rarely initiated in the prehospital setting.

Hurdles to Artificial Intelligence Deployment: Noise in Schemas and "Gold" Labels.

Despite frequent reports of imaging artificial intelligence (AI) that parallels human performance, clinicians often question the safety and robustness of AI products in practice. This work explores two underreported sources of noise that negatively affect imaging AI: variation in labeling schema definitions and noise in the labeling process. First, the overlap between the schemas of two publicly available datasets and a third-party vendor are compared, showing there is low agreement (<50%) between them.

Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.

Restrictive cardiomyopathy (RCM) is defined as increased myocardial stiffness and impaired diastolic relaxation leading to elevated ventricular filling pressures. Human variants in filamin C (FLNC) are linked to a variety of cardiomyopathies, and in this study, we investigate an in-frame deletion (c.7416_7418delGAA, p.

The evolving use of biomarkers in heart transplantation: Consensus of an expert panel.

In heart transplantation, the use of biomarkers to detect the risk of rejection has been evolving. In this setting, it is becoming less clear as to what is the most reliable test or combination of tests to detect rejection and assess the state of the alloimmune response. Therefore, a virtual expert panel was organized in heart and kidney transplantation to evaluate emerging diagnostics and how they may be best utilized to monitor and manage transplant patients.

Whole-body CD8 T cell visualization before and during cancer immunotherapy: a phase 1/2 trial.

Immune checkpoint inhibitors (ICIs), by reinvigorating CD8 T cell mediated immunity, have revolutionized cancer therapy. Yet, the systemic CD8 T cell distribution, a potential biomarker of ICI response, remains poorly characterized. We assessed safety, imaging dose and timing, pharmacokinetics and immunogenicity of zirconium-89-labeled, CD8-specific, one-armed antibody positron emission tomography tracer ZED88082A in patients with solid tumors before and ~30 days after starting ICI therapy (NCT04029181).

Assessment of Radiology Artificial Intelligence Software: A Validation and Evaluation Framework.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization.

U"AI" Testing: User Interface and Usability Testing of a Chest X-ray AI Tool in a Simulated Real-World Workflow.

To observe interactions of practicing radiologists with a chest x-ray AI tool and evaluate its usability and impact on workflow efficiency. Using a simulated clinical workflow and remote multi-monitor screensharing, we prospectively assessed the interactions of 10 staff radiologists (5-33 years of experience) with a PACS-embedded, regulatory-approved chest x-ray AI tool. Qualitatively, we collected feedback using a think-aloud method and post-testing semi-structured interview; transcript themes were categorized by: (1) AI tool features, (2) deployment considerations, and (3) broad human-AI interactions.

Alterations in the kallikrein-kinin system predict death after heart transplant.

Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort.

STK25 inhibits PKA signaling by phosphorylating PRKAR1A.

In the heart, protein kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta-adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits that inhibit the catalytic subunit until released by cAMP binding. Phosphorylation of type II regulatory subunits promotes PKA activation; however, the role of phosphorylation in type I regulatory subunits remain uncertain.

Changes in extracellular matrix in failing human non-ischemic and ischemic hearts with mechanical unloading.

Ischemic and non-ischemic cardiomyopathies have distinct etiologies and underlying disease mechanisms, which require in-depth investigation for improved therapeutic interventions. The goal of this study was to use clinically obtained myocardium from healthy and heart failure patients, and characterize the changes in extracellular matrix (ECM) in ischemic and non-ischemic failing hearts, with and without mechanical unloading. Using tissue engineering methodologies, we also investigated how diseased human ECM, in the absence of systemic factors, can influence cardiomyocyte function.

What factors have influenced quality of life in people with dementia and their family carers during the COVID-19 pandemic: a qualitative study.

Objectives: The COVID-19 pandemic has led to significant disruption to health and social care services. For people with dementia and their family carers this is problematic, as a group who rely on timely and responsive services to live well with the condition. This study has sought to understand how COVID-19 has affected the quality of life of people diagnosed with dementia and their family carers.

Unconventional Hysteretic Transition in a Charge Density Wave.

Hysteresis underlies a large number of phase transitions in solids, giving rise to exotic metastable states that are otherwise inaccessible. Here, we report an unconventional hysteretic transition in a quasi-2D material, EuTe_{4}. By combining transport, photoemission, diffraction, and x-ray absorption measurements, we observe that the hysteresis loop has a temperature width of more than 400 K, setting a record among crystalline solids.

Explainable artificial intelligence to predict the risk of side-specific extraprostatic extension in pre-prostatectomy patients.

Introduction: We aimed to develop an explainable machine learning (ML) model to predict side-specific extraprostatic extension (ssEPE) to identify patients who can safely undergo nerve-sparing radical prostatectomy using preoperative clinicopathological variables.

Methods: A retrospective sample of clinicopathological data from 900 prostatic lobes at our institution was used as the training cohort. Primary outcome was the presence of ssEPE.

Covid-19 and the quality of life of people with dementia and their carers-The TFD-C19 study.

Introduction: COVID-19 has placed unprecedented pressure on dementia health and social care systems worldwide. This has resulted in reduced services and support for people with dementia and their family carers. There are gaps in the evidence on the impact of the pandemic on Quality of Life (QoL).

Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone.

Background: Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABA) currents. However, we previously demonstrated that an endogenous neuroactive steroid epipregnanolone [(3β,5β)-3-hydroxypregnan-20-one] (EpiP) exerts potent peripheral analgesia and blocks T-type calcium currents while sparing GABA currents in rat sensory neurons. This study seeks to investigate the behavioral effects elicited by systemic administration of EpiP and to characterize its use as an adjuvant agent to commonly used general anesthetics (GAs).

Plasma kallikrein predicts primary graft dysfunction after heart transplant.

Background: Primary graft dysfunction (PGD) is the leading cause of early mortality after heart transplant. Pre-transplant predictors of PGD remain elusive and its etiology remains unclear.

Methods: Microvesicles were isolated from 88 pre-transplant serum samples and underwent proteomic evaluation using TMT mass spectrometry.

How artificial intelligence can help us 'Choose Wisely'.

The overuse of low value medical tests and treatments drives costs and patient harm. Efforts to address overuse, such as Choosing Wisely campaigns, typically rely on passive implementation strategies- a form of low reliability system change. Embedding guidelines into clinical decision support (CDS) software is a higher leverage approach to provide ordering suggestions through an interface embedded within the clinical workflow.

Characterizing early Canadian federal, provincial, territorial and municipal nonpharmaceutical interventions in response to COVID-19: a descriptive analysis.

Background: Nonpharmaceutical interventions (NPIs) are the primary tools to mitigate early spread of the coronavirus disease 2019 (COVID-19) pandemic; however, such policies are implemented variably at the federal, provincial or territorial, and municipal levels without centralized documentation. We describe the development of the comprehensive open Canadian Non-Pharmaceutical Intervention (CAN-NPI) data set, which identifies and classifies all NPIs implemented in regions across Canada in response to COVID-19, and provides an accompanying description of geographic and temporal heterogeneity.

Methods: We performed an environmental scan of government websites, news media and verified government social media accounts to identify NPIs implemented in Canada between Jan.