Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death.

Bibliometric Analysis: Bridging Informatics With Science.

Bibliometric analysis represents a new tool for classifying and quantitatively assessing bibliographic material (publications, citations, authors, institutions, etc) of a scientific discipline. Is a computer-assisted review and, therefore, it should follow the methodology of a systematic review. These analyses download bibliographic data from electronic databases analyzing them and extracting several indicators (such as the h-index). Analysis can be enhanced by adding scientific maps using specific software. These analyses are increasingly accepted in the medical literature to identify the most influential papers/authors/institutions on a given topic. During the last decade, there is a remarkable increase in the number of published bibliometric analysis articles.

Review Article: The Flagship of Evidence-Based Medicine.

Global literature is ever-growing and physicians rely on it for evidence-based decision making. Review articles summarize available literature and provide the current state of knowledge on a given topic. Various review types exist, the main ones being narrative and systematic reviews. The former are based on studies selected in an undefined manner. They express the authors' opinions of a given topic, lack a systematic search, and are prone to bias. By contrast, the latter represent an unbiased synthesis of knowledge on a particular topic and attempt to offer all relevant evidence. A systematic review may include a meta-analysis, which combines the results of quantitative studies using statistical techniques to provide a more precise summary of the evidence. With a dramatic increase in literature complexity, new "next-generation" types of reviews emerged to improve the quality of evidence synthesis: network meta-analysis, umbrella review, and meta-analysis of individual patient data, among others. Finally, scoping reviews are a special type, conducted as precursors to systematic reviews aiming to reveal specific knowledge gaps in a given subject.