Is clinical outcome of dengue-virus infections influenced by coagulation and fibrinolysis? A critical review of the evidence.

Item does not contain fulltextDespite efforts to elucidate the pathogenesis of dengue fever, the progression into severe disease remains poorly understood. In-vitro findings suggest that coagulopathy and disturbances in fibrinolysis have a pivotal role in the pathophysiology. If disturbances in these processes are predictive of clinical outcome in this disease, there could be important consequences for both diagnosis and treatment. We have critically reviewed publications on this topic to assess whether there is an association between activation of coagulation and fibrinolysis and clinical outcome of dengue-virus infections. In general, the selected studies showed activation of both the coagulation and fibrinolytic systems in this infection. The activation was more pronounced in severe infections and in cases with a poor clinical outcome. However, the findings were not consistent, and owing to a lack of detailed information on characteristics of patients, disease, and study design, we could not ascertain whether inconsistencies were caused by differences in these characteristics, selection bias, or confounding factors. We conclude that an association between activation of coagulation and fibrinolysis and clinical outcome of dengue-virus infections is conceivable but has been inadequately assessed and that methodologically sound studies, complemented with complete and reliable reporting, are needed to show whether there is a true association

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org)