Assembling the RNA therapeutics toolbox.

From the approval of COVID-19 mRNA vaccines to the 2023 Nobel Prize awarded for nucleoside base modifications, RNA therapeutics have entered the spotlight and are transforming drug development. While the term "RNA therapeutics" has been used in various contexts, this review focuses on treatments that utilize RNA as a component or target RNA for therapeutic effects. We summarize the latest advances in RNA-targeting tools and RNA-based technologies, including but not limited to mRNA, antisense oligos, siRNAs, small molecules and RNA editors.

Genome-wide studies in prostate cancer poised liquid biopsy as a molecular discovery tool.

Liquid biopsy is emerging as an intriguing tool in clinical disease detection and monitoring. Compared to a standard tissue biopsy, performing a liquid biopsy incurs minimal invasiveness, captures comprehensive disease representation, and can be more sensitive at an early stage. Recent genome-wide liquid biopsy studies in prostate cancer analyzing plasma samples have provided insights into the genome and epigenome dynamics during disease progression.

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling.

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor.

Conversational Agents in Health Care: Scoping Review of Their Behavior Change Techniques and Underpinning Theory.

Background: Conversational agents (CAs) are increasingly used in health care to deliver behavior change interventions. Their evaluation often includes categorizing the behavior change techniques (BCTs) using a classification system of which the BCT Taxonomy v1 (BCTTv1) is one of the most common. Previous studies have presented descriptive summaries of behavior change interventions delivered by CAs, but no in-depth study reporting the use of BCTs in these interventions has been published to date.

Molecular Determinants of Tissue Specificity of Flavivirus Nonstructural Protein 1 Interaction with Endothelial Cells.

Members of the mosquito-borne flavivirus genus such as dengue (DENV), West Nile (WNV), and Zika (ZIKV) viruses cause distinct diseases and affect different tissues. We previously found that the secreted flaviviral nonstructural protein 1 (NS1) interacts with endothelial cells and disrupts endothelial barrier function in a tissue-specific manner consistent with the disease tropism of the respective viruses. However, the underlying molecular mechanism of this tissue-specific NS1-endothelial cell interaction is not well understood.

A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes.

Rickettsia species of the spotted fever group are arthropod-borne obligate intracellular bacteria that can cause mild to severe human disease. These bacteria invade host cells, replicate in the cell cytosol, and spread from cell to cell. To access the host cytosol and avoid immune detection, they escape membrane-bound vacuoles by expressing factors that disrupt host membranes.

The Basis and Promise of Programmable RNA Editing and Modification.

One key advantage of RNA over genomic editing is its temporary effects. Aside from current use of DNA-targeting CRISPR-Cas9, the more recently discovered CRISPR-Cas13 has been explored as a means of editing due to its RNA-targeting capabilities. Specifically, there has been a recent interest in identifying and functionally characterizing biochemical RNA modifications, which has spurred a new field of research known as "epitranscriptomics".

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling.

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of this pathology are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to trigger barrier dysfunction and vascular leak , independently of viral replication and the ACE2 receptor.

#EatingDisorderRecovery: a qualitative content analysis of eating disorder recovery-related posts on Instagram.

Purpose: Limited research has evaluated the role of Social Networking Sites (SNS) in eating disorder (ED) recovery. While research has demonstrated the deleterious effects of pro-ED SNS content, less is known regarding SNS content documenting ED recovery. This study evaluates orientation towards help-seeking, ongoing ED warning signs and recovery themes on ED recovery SNS hashtags.

Choice of Behavioral Change Techniques in Health Care Conversational Agents: Protocol for a Scoping Review.

Background: Conversational agents or chatbots are computer programs that simulate conversations with users. Conversational agents are increasingly used for delivery of behavior change interventions in health care. Behavior change is complex and comprises the use of one or several components collectively known as behavioral change techniques (BCTs).

Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction.

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown.

The relationship between variability in baseball pitching kinematics and consistency in pitch location.

The purpose of this study was to explore the relationship between variability in pitching kinematics and consistency in pitch location. Data were collected for 47 healthy baseball pitchers throwing ten full-effort fastballs to the centre of the strike zone. For each pitch, 20 kinematic parameters were calculated with an automated motion capture system while pitch location was measured with a PITCHf/x system.

Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation.

Arthropod-borne flaviviruses cause life-threatening diseases associated with endothelial hyperpermeability and vascular leak. We recently found that vascular leak can be triggered by dengue virus (DENV) non-structural protein 1 (NS1) via the disruption of the endothelial glycocalyx-like layer (EGL). However, the molecular determinants of NS1 required to trigger EGL disruption and the cellular pathway(s) involved remain unknown.

The influence of mound height on baseball movement and pitching biomechanics.

Objectives: To determine whether mound height is associated with baseball movement (velocity, spin and break) and baseball pitching biomechanics (kinematics and kinetics).

Design: Controlled laboratory study.

Methods: Twenty collegiate baseball pitchers threw five fastballs and five curveballs from four different mound heights (15cm, 20cm, 25cm, 30cm) in a randomized order.