Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines.

Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical-molecular-biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition.

Pre-procedural determination of device size in left atrial appendage occlusion using three-dimensional cardiac computed tomography.

The complex structure of the left atrial appendage (LAA) brings limitations to the two-dimensional-based LAA occlusion (LAAO) size prediction system using transesophageal echocardiography. The LAA anatomy can be evaluated more precisely using three-dimensional images from cardiac computed tomography (CT); however, there is lack of data regarding which parameter to choose from CT-based images during pre-procedural planning of LAAO. We aimed to assess the accuracy of measurements derived from cardiac CT images for selecting LAAO devices.

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients.

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in .

The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here, we utilized proteomics, RNA sequencing, autoantibody arrays, and B cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, and complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases.

Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease.

Purpose: Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes stroke and silent cerebral infarct (SCI). Our aim was to identify markers of brain injury in SCD.

Experimental Design: Plasma proteomes were analyzed using a sequential separation approach of hemoglobin (Hb) and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion, and tandem mass spectrometry.

Safety First: An Ambulation Protocol for Patients With Pulmonary Artery Catheters.

Background: Patients with indwelling pulmonary artery catheters have historically been excluded from participating in early mobility programs because of the concern for catheter-related complications. However, this practice conflicts with the benefits accrued from early mobilization.

Objective: The purposes of this quality improvement project were to develop and implement a standardized ambulation protocol for patients with a pulmonary artery catheter in a cardiac surgery intensive care unit and to assess and support safe ambulation practices while preventing adverse events in patients with pulmonary artery catheters.

Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study.

Background: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.

Methods: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case).

Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: A prospective study.

Background And Aims: We sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects.

Methods: We studied 1069 subjects (age 58.2 ± 8.

Next-Generation Hardware Advances in CT: Cardiac Applications.

Impending major hardware advances in cardiac CT include three areas: ultra-high-resolution (UHR) CT, photon-counting CT, and phase-contrast CT. Cardiac CT is a particularly demanding CT application that requires a high degree of temporal resolution, spatial resolution, and soft-tissue contrast in a moving structure. In this review, cardiac CT is used to highlight the strengths of these technical advances.

CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury.

Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus of Hsc70-interacting protein (CHIP) is an important regulator of proteostasis in many cells, having E3-ligase and chaperone functions and often directing damaged proteins towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation.

Alterra Adaptive Prestent and SAPIEN 3 THV for Congenital Pulmonic Valve Dysfunction: An Early Feasibility Study.

Objectives: The aim of this study was to demonstrate the safety and functionality of the Alterra Adaptive Prestent and SAPIEN 3 transcatheter heart valve (THV) in patients with dysfunctional, dilated right ventricular outflow tract (RVOT) greater or equal to moderate pulmonary regurgitation (PR).

Background: Significant variations in the size and morphology of the RVOT affect the placement of transcatheter pulmonary valves. The Alterra Prestent internally reduces and reconfigures the RVOT, providing a stable landing zone for the 29-mm SAPIEN 3 THV.

Elucidating Citrullination by Mass Spectrometry and Its Role in Disease Pathogenesis.

This review focuses on discussing key mechanisms in disease pathogenesis mediated by the protein post-translational modification citrullination. These processes are discussed in depth in the context of complex diseases such as rheumatoid arthritis, cancer, central nervous system disorders, and cardiovascular disease. Additionally, a critical evaluation of challenges in laboratory detection of citrullination sites is also outlined.

Lysine and Arginine Protein Post-translational Modifications by Enhanced DIA Libraries: Quantification in Murine Liver Disease.

Proteoforms containing post-translational modifications (PTMs) represent a degree of functional diversity only harnessed through analytically precise simultaneous quantification of multiple PTMs. Here we present a method to accurately differentiate an unmodified peptide from its PTM-containing counterpart through data-independent acquisition-mass spectrometry, leveraging small precursor mass windows to physically separate modified peptidoforms from each other during MS2 acquisition. We utilize a lysine and arginine PTM-enriched peptide assay library and site localization algorithm to simultaneously localize and quantify seven PTMs including mono-, di-, and trimethylation, acetylation, and succinylation in addition to total protein quantification in a single MS run without the need to enrich experimental samples.

Association Between Atrial Fibrillation and Sudden Cardiac Death: Pathophysiological and Epidemiological Insights.

Emerging evidence suggests that atrial fibrillation (AF) may be associated with an increased risk of sudden cardiac death (SCD). However, AF shares risk factors with numerous cardiac conditions, including coronary heart disease and heart failure-the 2 most common substrates for SCD-making the AF-SCD relationship particularly challenging to address. A careful consideration of confounding factors is essential, since interventions for AF will be effective in reducing SCD only if there is a causal association between these 2 conditions.

Depression in Heart Failure: A Systematic Review.

: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure.

Sex-related differences in outcomes after coronary artery bypass surgery-A patient-level pooled analysis of randomized controlled trials: rationale and study protocol.

Introduction: The impact of sex on the outcomes after coronary artery bypass grafting (CABG) is controversial. The majority of CABG studies are retrospectively collected clinical or registry data, women comprise only a minority, and the reported findings represent the male predominated cohort. This individual patient meta-analysis is aimed at evaluating sex-related differences in outcomes after CABG using high quality data from randomized controlled trials (RCTs).

Parkin, an E3 ubiquitin ligase, enhances airway mitochondrial DNA release and inflammation.

Introduction: Parkin (Park2), an E3 ubiquitin ligase, is critical to maintain mitochondrial function by regulating mitochondrial biogenesis and degradation (mitophagy), but recent evidence suggests the involvement of Parkin in promoting inflammation. In the present study, we determined if Parkin regulates airway mitochondrial DNA (mtDNA) release and inflammatory responses to type 2 cytokine interleukin (IL)-13 and allergens.

Methods: We measured Parkin mRNA expression in brushed bronchial epithelial cells and mtDNA release in the paired bronchoalveolar lavage fluid (BALF) from normal subjects and asthmatics.

Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring.

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs.

PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks.

Recent surges in mass spectrometry-based proteomics studies demand a concurrent rise in speedy and optimized data processing tools and pipelines. Although several stand-alone bioinformatics tools exist that provide protein-protein interaction (PPI) data, we developed Protein Interaction Network Extractor (PINE) as a fully automated, user-friendly, graphical user interface application for visualization and exploration of global proteome and post-translational modification (PTM) based networks. PINE also supports overlaying differential expression, statistical significance thresholds, and PTM sites on functionally enriched visualization networks to gain insights into proteome-wide regulatory mechanisms and PTM-mediated networks.

Repeatability of quantitative pericoronary adipose tissue attenuation and coronary plaque burden from coronary CT angiography.

Background: High pericoronary adipose tissue (PCAT) attenuation and non-calcified plaque burden (NCP) measured from coronary CT angiography (CTA) have been implicated in future cardiac events. We aimed to evaluate the interobserver and intraobserver repeatability of PCAT attenuation and NCP burden measurement from CTA, in a sub-study of the prospective SCOT-HEART trial.

Methods: Fifty consecutive CTAs from participants of the CT arm of the prospective SCOT-HEART trial were included.

Quality Control and Outlier Detection of Targeted Mass Spectrometry Data from Multiplex Protein Panels.

Increased throughput as well as increased multiplexing of liquid chromatography coupled to selected reaction monitoring mass spectrometry (LC-SRM-MS) assays for protein quantification challenges routine data analysis. Despite the measurement of multiple transitions from multiple peptides, for clinical applications a single (quantifier) transition from one (quantifier) signature peptide is used to represent the protein quantity with most data used solely to validate the quantifier result. To support the generation of reliable protein results from multiplexed LC-SRM-MS assays with large sample numbers, we developed a data analysis process for quality control and outlier detection using data from an 11-protein multiplex LC-SRM-MS method for dried blood samples (195 492 chromatographic peaks from 1481 samples * 11 proteins * 2 peptides * 3 transitions * 2 isotopologues).

COVID-19 and the Heart.

Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects.