SARS-CoV-2 3CL (main protease) regulates caspase activation of gasdermin-D/E pores leading to secretion and extracellular activity of 3CL.

SARS-CoV-2 3C-like protease (3CL or M) cleaves the SARS-CoV-2 polyprotein and >300 intracellular host proteins to enhance viral replication. By lytic cell death following gasdermin (GSDM) pore formation in cell membranes, antiviral pyroptosis decreases 3CL expression and viral replication. Unexpectedly, 3CL and nucleocapsid proteins undergo unconventional secretion from infected cells via caspase-activated GSDMD/E pores in the absence of cell lysis.

Platelet signaling at the nexus of innate immunity and rheumatoid arthritis.

Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation of the synovial tissues and progressive destruction of bone and cartilage. The inflammatory response and subsequent tissue degradation are orchestrated by complex signaling networks between immune cells and their products in the blood, vascular endothelia and the connective tissue cells residing in the joints. Platelets are recognized as immune-competent cells with an important role in chronic inflammatory diseases such as RA.

Multi-Ontology Refined Embeddings (MORE): A hybrid multi-ontology and corpus-based semantic representation model for biomedical concepts.

Objective: Currently, a major limitation for natural language processing (NLP) analyses in clinical applications is that concepts are not effectively referenced in various forms across different texts. This paper introduces Multi-Ontology Refined Embeddings (MORE), a novel hybrid framework that incorporates domain knowledge from multiple ontologies into a distributional semantic model, learned from a corpus of clinical text.

Materials And Methods: We use the RadCore and MIMIC-III free-text datasets for the corpus-based component of MORE.

Evaluating effectiveness of information visualizations using cognitive fit theory: A neuroergonomics approach.

Information visualizations may be evaluated from the perspective of how they match tasks that must be performed with them, a cognitive fit perspective. However, there is a gap between the high-level references made to cognitive fit and the low-level ability to identify and measure it during human interaction with visualizations. We bridge this gap by using an electroencephalography metric derived from frontal midline theta power and parietal alpha power, known as the task load index, to determine if cognitive effort measured at the level of cortical activity is less when cognitive fit is present compared to when cognitive fit is not.

Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development.

Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development.

Automatic post-stroke lesion segmentation on MR images using 3D residual convolutional neural network.

In this paper, we demonstrate the feasibility and performance of deep residual neural networks for volumetric segmentation of irreversibly damaged brain tissue lesions on T1-weighted MRI scans for chronic stroke patients. A total of 239 T1-weighted MRI scans of chronic ischemic stroke patients from a public dataset were retrospectively analyzed by 3D deep convolutional segmentation models with residual learning, using a novel zoom-in&out strategy. Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and Hausdorff distance (HD) of the identified lesions were measured by using manual tracing of lesions as the reference standard.

Middle-aged death and taxes in the USA: Association of state tax burden and expenditures in 2005 with survival from 2006 to 2015.

Background: Longevity in the United States ranks below most other Western nations despite spending more on healthcare per capita than any other country. Across the world, mortality has been declining, but in the USA the trend toward improvement has stalled in some middle-aged demographic groups. Cross-national studies suggest that social welfare is positively associated with longevity.

Usability testing of existing type 2 diabetes mellitus websites.

Background: Given the significant increase in the use of the internet as an educational tool for diabetes, very little research has been published on the usability of healthcare websites, even though it is a determining factor for user satisfaction.

Objective: The aim of this study is to evaluate and critique the interfaces of existing diabetes websites for usability concerns and provide design solutions for improvement. Emphasis is placed on Type 2 Diabetes Mellitus since it is the most common and life threatening form of diabetes.

A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome.

The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences.

The PAZAR database unites independently created and maintained data collections of transcription factor and regulatory sequence annotation. The flexible PAZAR schema permits the representation of diverse information derived from experiments ranging from biochemical protein-DNA binding to cellular reporter gene assays. Data collections can be made available to the public, or restricted to specific system users.