45 research outputs found
Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review
BACKGROUND Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION PROSPERO 2020 CRD42020175648
MicroRNA Genes Derived from Repetitive Elements and Expanded by Segmental Duplication Events in Mammalian Genomes
MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene
expression by targeting mRNAs for translation repression or mRNA degradation.
Many miRNAs are being discovered and studied, but in most cases their origin,
evolution and function remain unclear. Here, we characterized miRNAs derived
from repetitive elements and miRNA families expanded by segmental duplication
events in the human, rhesus and mouse genomes. We applied a comparative genomics
approach combined with identifying miRNA paralogs in segmental duplication pair
data in a genome-wide study to identify new homologs of human miRNAs in the
rhesus and mouse genomes. Interestingly, using segmental duplication pair data,
we provided credible computational evidence that two miRNA genes are located in
the pseudoautosomal region of the human Y chromosome. We characterized all the
miRNAs whether they were derived from repetitive elements or not and identified
significant differences between the repeat-related miRNAs (RrmiRs) and
non-repeat-derived miRNAs in (1) their location in protein-coding and intergenic
regions in genomes, (2) the minimum free energy of their hairpin structures, and
(3) their conservation in vertebrate genomes. We found some lineage-specific
RrmiR families and three lineage-specific expansion families, and provided
evidence indicating that some RrmiR families formed and expanded during
evolutionary segmental duplication events. We also provided computational and
experimental evidence for the functions of the conservative RrmiR families in
the three species. Together, our results indicate that repetitive elements
contribute to the origin of miRNAs, and large segmental duplication events could
prompt the expansion of some miRNA families, including RrmiR families. Our study
is a valuable contribution to the knowledge of evolution and function of
non-coding region in genome
Genome-wide microRNA screening in Nile tilapia reveals pervasive isomiRs’ transcription, sex-biased arm switching and increasing complexity of expression throughout development
MicroRNAs (miRNAs) are key regulators of gene expression in multicellular organisms. The elucidation of miRNA function and evolution depends on the identification and characterization of miRNA repertoire of strategic organisms, as the fast-evolving cichlid fishes. Using RNA-seq and comparative genomics we carried out an in-depth report of miRNAs in Nile tilapia (Oreochromis niloticus), an emergent model organism to investigate evo-devo mechanisms. Five hundred known miRNAs and almost one hundred putative novel vertebrate miRNAs have been identified, many of which seem to be teleost-specific, cichlid-specific or tilapia-specific. Abundant miRNA isoforms (isomiRs) were identified with modifications in both 5p and 3p miRNA transcripts. Changes in arm usage (arm switching) of nine miRNAs were detected in early development, adult stage and even between male and female samples. We found an increasing complexity of miRNA expression during ontogenetic development, revealing a remarkable synchronism between the rate of new miRNAs recruitment and morphological changes. Overall, our results enlarge vertebrate miRNA collection and reveal a notable differential ratio of miRNA arms and isoforms influenced by sex and developmental life stage, providing a better picture of the evolutionary and spatiotemporal dynamics of miRNAs
Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI
A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico, evaluation, but few have yet demonstrated real benefit to patient care. Early stage clinical evaluation is important to assess an AI system’s actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use, and pave the way to further large scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multistakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two round, modified Delphi process to collect and analyse expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 predefined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. 123 experts participated in the first round of Delphi, 138 in the second, 16 in the consensus meeting, and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI specific reporting items (made of 28 subitems) and 10 generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we have developed a guideline comprising key items that should be reported in early stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings