Frequency of Electrocardiogram-Defined Cardiac Conduction Disorders in a Multi-Institutional Primary Care Cohort.

Background: Disorders affecting cardiac conduction are associated with substantial morbidity. Understanding the epidemiology and risk factors for conduction disorders may enable earlier diagnosis and preventive efforts.

Objectives: The purpose of this study was to quantify contemporary frequency and risk factors for electrocardiogram (ECG)-defined cardiac conduction disorders in a large multi-institutional primary care sample.

Deep Learning-Enabled Assessment of Left Heart Structure and Function Predicts Cardiovascular Outcomes.

Background: Deep learning interpretation of echocardiographic images may facilitate automated assessment of cardiac structure and function.

Objectives: We developed a deep learning model to interpret echocardiograms and examined the association of deep learning-derived echocardiographic measures with incident outcomes.

Methods: We trained and validated a 3-dimensional convolutional neural network model for echocardiographic view classification and quantification of left atrial dimension, left ventricular wall thickness, chamber diameter, and ejection fraction.

Artificial intelligence-enabled classification of hypertrophic heart diseases using electrocardiograms.

Background: Differentiating among cardiac diseases associated with left ventricular hypertrophy (LVH) informs diagnosis and clinical care.

Objective: To evaluate if artificial intelligence-enabled analysis of the 12-lead electrocardiogram (ECG) facilitates automated detection and classification of LVH.

Methods: We used a pretrained convolutional neural network to derive numerical representations of 12-lead ECG waveforms from patients in a multi-institutional healthcare system who had cardiac diseases associated with LVH (n = 50,709), including cardiac amyloidosis (n = 304), hypertrophic cardiomyopathy (n = 1056), hypertension (n = 20,802), aortic stenosis (n = 446), and other causes (n = 4766).

Benefits, limitations and implementation issues for integrating organic foods into hospital foodservices: a systematic review.

Background: Public institutions have the opportunity to implement environmental sustainability policies through leveraging their buying potential. Given the role of hospitals within the food system, the implementation of sustainable initiatives into hospital foodservices is a priority. Compared to conventional agricultural methods, organic food production uses more sustainable practices and warrants consideration for utilisation in hospitals.

One Clinician Is All You Need-Cardiac Magnetic Resonance Imaging Measurement Extraction: Deep Learning Algorithm Development.

Background: Cardiac magnetic resonance imaging (CMR) is a powerful diagnostic modality that provides detailed quantitative assessment of cardiac anatomy and function. Automated extraction of CMR measurements from clinical reports that are typically stored as unstructured text in electronic health record systems would facilitate their use in research. Existing machine learning approaches either rely on large quantities of expert annotation or require the development of engineered rules that are time-consuming and are specific to the setting in which they were developed.

Cohort design and natural language processing to reduce bias in electronic health records research.

Electronic health record (EHR) datasets are statistically powerful but are subject to ascertainment bias and missingness. Using the Mass General Brigham multi-institutional EHR, we approximated a community-based cohort by sampling patients receiving longitudinal primary care between 2001-2018 (Community Care Cohort Project [C3PO], n = 520,868). We utilized natural language processing (NLP) to recover vital signs from unstructured notes.

Expansion of Insurance Under the Affordable Care Act and Invasive Management of Acute Myocardial Infarction.

Background: The Affordable Care Act of 2010 extended health insurance through expansion of Medicaid and subsidies for commercial insurance. Prior work has produced differing results in associating expanded insurance with improvements in health care processes and outcomes. Evaluating specific mechanisms of care processes and their association with insurance expansion may help reconcile those results.

Accelerometer-derived physical activity and risk of atrial fibrillation.

Aims: Physical activity may be an important modifiable risk factor for atrial fibrillation (AF), but associations have been variable and generally based on self-reported activity.

Methods And Results: We analysed 93 669 participants of the UK Biobank prospective cohort study without prevalent AF who wore a wrist-based accelerometer for 1 week. We categorized whether measured activity met the standard recommendations of the European Society of Cardiology, American Heart Association, and World Health Organization [moderate-to-vigorous physical activity (MVPA) ≥150 min/week].

Use of Machine Learning Models to Predict Death After Acute Myocardial Infarction.

Importance: Accurate prediction of adverse outcomes after acute myocardial infarction (AMI) can guide the triage of care services and shared decision-making, and novel methods hold promise for using existing data to generate additional insights.

Objective: To evaluate whether contemporary machine learning methods can facilitate risk prediction by including a larger number of variables and identifying complex relationships between predictors and outcomes.

Design, Setting, And Participants: This cohort study used the American College of Cardiology Chest Pain-MI Registry to identify all AMI hospitalizations between January 1, 2011, and December 31, 2016.

Enhancing the prediction of acute kidney injury risk after percutaneous coronary intervention using machine learning techniques: A retrospective cohort study.

Background: The current acute kidney injury (AKI) risk prediction model for patients undergoing percutaneous coronary intervention (PCI) from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) employed regression techniques. This study aimed to evaluate whether models using machine learning techniques could significantly improve AKI risk prediction after PCI.

Methods And Findings: We used the same cohort and candidate variables used to develop the current NCDR CathPCI Registry AKI model, including 947,091 patients who underwent PCI procedures between June 1, 2009, and June 30, 2011.

Altered N-Linked Glycosylation in Follicular Lymphoma and Chronic Lymphocytic Leukemia: Involvement in Pathogenesis and Potential Therapeutic Targeting.

B-cell antigen receptor (BCR) expression is indispensable for survival of most B-cell malignancies. In follicular lymphoma (FL), N-linked glycosylation sites are introduced in the immunoglobulin (Ig) variable region genes. Oligosaccharides added to the acquired sites are unusually of the high-mannose type.

Discovery of temporal and disease association patterns in condition-specific hospital utilization rates.

Identifying temporal variation in hospitalization rates may provide insights about disease patterns and thereby inform research, policy, and clinical care. However, the majority of medical conditions have not been studied for their potential seasonal variation. The objective of this study was to apply a data-driven approach to characterize temporal variation in condition-specific hospitalizations.

Enhancer modeling uncovers transcriptional signatures of individual cardiac cell states in Drosophila.

Here we used discriminative training methods to uncover the chromatin, transcription factor (TF) binding and sequence features of enhancers underlying gene expression in individual cardiac cells. We used machine learning with TF motifs and ChIP data for a core set of cardiogenic TFs and histone modifications to classify Drosophila cell-type-specific cardiac enhancer activity. We show that the classifier models can be used to predict cardiac cell subtype cis-regulatory activities.

Distinct processing of the pre-B cell receptor and the B cell receptor.

It has been recently demonstrated that while oligosaccharide moieties of μ heavy chains in the B-cell receptor (BCR) are of the complex type as expected, those of the pre-BCR on the surface of pre-B cells contain oligosaccharide moieties of the high-mannose type only. This is unique, because high-mannose glycans are generally restricted to the endoplasmic reticulum and not presented on the surface of mammalian cells. In the present study, we examined the processing of the unusually glycosylated μ heavy chains in pre-B cells.

Enhanced therapeutic effect of B cell-depleting anti-CD20 antibodies upon combination with in-situ dendritic cell vaccination in advanced lymphoma.

The present standard of care for B cell non-Hodgkin's lymphoma includes the anti-CD20 monoclonal antibody rituximab. Although combination treatments with chemotherapy and rituximab improved the duration of remissions and overall survival in indolent B cell lymphoma, the disease is essentially incurable. Thus, new therapeutic approaches are needed.

All oligosaccharide moieties of the μ chains in the pre-BCR are of the high-mannose type.

Although it is well established that pre-BCR signaling governs proliferation and differentiation during B cell development, the components of the pre-BCR that are important for signaling are a matter of controversy. It has been suggested that signaling by the μ heavy chains of the pre-BCR induces survival and differentiation of pre-B cells, while the λ5 part of the pre-BCR is essential for proliferation and clonal expansion. However, the mechanism by which pre-BCR μ chains initiate differentiation signals is not clear.

The MAPK/ERK and PI3K pathways additively coordinate the transcription of recombination-activating genes in B lineage cells.

Rag-1 and Rag-2 are essential for the construction of the BCR repertoire. Regulation of Rag gene expression is tightly linked with BCR expression and signaling during B cell development. Earlier studies have shown a major role of the PI(3)K/Akt pathway in regulating the transcription of Rag genes.

Prolonged endoplasmic reticulum stress promotes mislocalization of immunoglobulins to the cytoplasm.

Signal peptide-dependent insertion of newly synthesized proteins into the endoplasmic reticulum (ER) is a multi-step process, whose fidelity varies with the identity of the protein and the cell type. ER translocation of prions is sensitive to conditions of acute ER stress in a manner that pre-emptively prevents their aggregation and proteo-toxicity. While this has been documented for extreme ER stress conditions and for a special type of proteins, the impact of chronic ER stress on protein translocation in general has not been well characterized.

Synergistic effect of dendritic cell vaccination and anti-CD20 antibody treatment in the therapy of murine lymphoma.

Indolent B-cell lymphomas are characterized by repeated remissions and relapses with most patients eventually dying of the disease. Although combination treatments with chemotherapy and the anti-CD20 antibody rituximab improved duration of remissions and overall survival, the disease is essentially incurable. Thus, novel therapeutic approaches are needed.

Dendritic cell-based therapeutic vaccination against myeloma: vaccine formulation determines efficacy against light chain myeloma.

Multiple myeloma is an incurable plasma cell malignancy. Immunotherapy in myeloma patients had limited success to date. We have previously demonstrated that dendritic cells (DCs) pulsed with autologous Ig Id induced Id-reactive CD8(+) T cells and protection against a myeloma tumor challenge.

Growth inhibition of myeloma cells by anti-idiotype antibodies in the absence of membrane-bound immunoglobulin.

Immunoglobulins are expressed as membrane-bound or secreted forms. Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor-specific antigens that may be targeted for immunotherapy.

Building of the tetraspanin web: distinct structural domains of CD81 function in different cellular compartments.

The tetraspanin web is composed of a network of tetraspanins and their partner proteins that facilitate cellular interactions and fusion events by an unknown mechanism. Our aim was to unravel the web partnership between the tetraspanin CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that CD81 plays multiple roles in the processing, intracellular trafficking, and membrane functions of CD19.

B-cell lymphoma and myeloma protection induced by idiotype vaccination with dendritic cells is mediated entirely by T cells in mice.

Immunoglobulin idiotypes (Id) of malignant B cells are tumor-specific antigens that may be targeted for immunotherapy. Id-directed immunotherapy by immunization with autologous Id has been initiated in clinical trials to control residual disease in B-cell lymphoma and multiple myeloma. The effector mechanisms responsible for destruction of B-cell tumors are a controversial issue.

Anti-idiotype x anti-CD44 bispecific antibodies inhibit invasion of lymphoid organs by B cell lymphoma.

The demonstration that Abs to adhesion molecules can block tumor metastasis suggested their use for therapy. However, such Abs affect nonmalignant cells as well. To circumvent this adverse effect, we proposed the use of bispecific Abs that bind simultaneously to an adhesion receptor and to a tumor-specific Ag.

Anti-idiotype x anti-LFA-1 bispecific antibodies inhibit metastasis of B cell lymphoma.

Abs to adhesion molecules can block tumor metastasis. However, they may also block the function of normal cells. To circumvent this adverse effect, we proposed the use of bispecific Abs that bind simultaneously to an adhesion receptor and to a tumor-specific Ag.