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1.
J Clin Epidemiol ; 149: 195-202, 2022 09.
Article in English | MEDLINE | ID: mdl-35597369

ABSTRACT

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 Living OVerview of Evidence (COVID-19 L·OVE) is a public repository and classification platform for COVID-19 articles. The repository contains more than 430,000 articles as of September 20, 2021 and intends to provide a one-stop shop for COVID-19 evidence. Considering that systematic reviews conduct high-quality searches, this study assesses the comprehensiveness and currency of the repository against the total number of studies in a representative sample of COVID-19 systematic reviews. METHODS: Our sample was generated from all the studies included in the systematic reviews of COVID-19 published during April 2021. We estimated the comprehensiveness of COVID-19 L·OVE repository by determining how many of the individual studies in the sample were included in the COVID-19 L·OVE repository. We estimated the currency as the percentage of studies that was available in the COVID-19 L·OVE repository at the time the systematic reviews conducted their own search. RESULTS: We identified 83 eligible systematic reviews that included 2,132 studies. COVID-19 L·OVE had an overall comprehensiveness of 99.67% (2,125/2,132). The overall currency of the repository, that is, the proportion of articles that would have been obtained if the search of the reviews was conducted in COVID-19 L·OVE instead of searching the original sources, was 96.48% (2,057/2,132). Both the comprehensiveness and the currency were 100% for randomized trials (82/82). CONCLUSION: The COVID-19 L·OVE repository is highly comprehensive and current. Using this repository instead of traditional manual searches in multiple databases can save a great amount of work to people conducting systematic reviews and would improve the comprehensiveness and timeliness of evidence syntheses. This tool is particularly important for supporting living evidence synthesis processes.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Publications
2.
JCI Insight ; 6(5)2021 03 08.
Article in English | MEDLINE | ID: mdl-33476303

ABSTRACT

TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 that catalyzes ubiquitin activation, the first step in the ubiquitylation cascade. Based on its preclinical efficacy and tolerability, TAK-243 has been advanced to phase I clinical trials in advanced malignancies. Nonetheless, the determinants of TAK-243 sensitivity remain largely unknown. Here, we conducted a genome-wide CRISPR/Cas9 knockout screen in acute myeloid leukemia (AML) cells in the presence of TAK-243 to identify genes essential for TAK-243 action. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout confers resistance to TAK-243 in vitro and in vivo. Knockout of BEND3 dampened TAK-243 effects on ubiquitylation, proteotoxic stress, and DNA damage response. BEND3 knockout upregulated the ATP-binding cassette efflux transporter breast cancer resistance protein (BCRP; ABCG2) and reduced the intracellular levelsof TAK-243. TAK-243 sensitivity correlated with BCRP expression in cancer cell lines of different origins. Moreover, chemical inhibition and genetic knockdown of BCRP sensitized intrinsically resistant high-BCRP cells to TAK-243. Thus, our data demonstrate that BEND3 regulates the expression of BCRP for which TAK-243 is a substrate. Moreover, BCRP expression could serve as a predictor of TAK-243 sensitivity.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Drug Resistance, Neoplasm , Enzyme Inhibitors , Gene Expression Regulation, Neoplastic , Leukemia, Myeloid, Acute , Neoplasm Proteins/metabolism , Pyrazoles , Pyrimidines , Repressor Proteins/metabolism , Sulfides , Sulfonamides , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , ATP-Binding Cassette Transporters , Animals , CRISPR-Cas Systems , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Genome , Humans , Leukemia, Myeloid, Acute/drug therapy , Male , Mice , Neoplasm Proteins/genetics , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Repressor Proteins/genetics , Sulfides/pharmacology , Sulfides/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use
3.
Recent Pat Biotechnol ; 14(3): 194-202, 2020.
Article in English | MEDLINE | ID: mdl-32164521

ABSTRACT

BACKGROUND: There are several methods for the quantification of biomass in SSF, such as glucosamine measurement, ergosterol content, protein concentration, change in dry weight or evolution of CO2 production. However, all have drawbacks when obtaining accurate data on the progress of the SSF due to the dispersion in cell growth on the solid substrate, and the difficulty encountered in separating the biomass. Studying the disadvantages associated with the process of biomass quantification in SSF, the monitoring of the growth of biomass by a technique known as digital image processing (DIP), consists of obtaining information on the production of different compounds during fermentation, using colorimetric methods based on the pixels that are obtained from photographs. OBJECTIVE: The purpose of this study was to know about the state of the technology and the advantages of DIP. METHODS: The methodology employed four phases; the first describes the search equations for the SSF and the DIP. A search for patents related to SSF and DIP carried out in the Free Patents Online and Patent inspiration databases. Then there is the selection of the most relevant articles in each of the technologies. As a third step, modifications for obtaining the best adjustments were also carried out. Finally, the analysis of the results was done and the inflection years were determined by means of six mathematical models widely studied. RESULTS: For these models, the inflection years were 2018 and 2019 for both the SSF and the DIP. Additionally, the main methods for the measurement of biomass in SSF were found, and are also indicated in the review, as DIP measurement processes have already been carried out using the same technology. CONCLUSION: In addition, the DIP has shown satisfactory results and could be an interesting alternative for biomass measurement in SSF, due to its ease and versatility.


Subject(s)
Colorimetry/methods , Fermentation/physiology , Fungi/metabolism , Image Processing, Computer-Assisted/methods , Models, Statistical , Biomass , Biotechnology/methods , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Databases, Bibliographic , Ergosterol/analysis , Ergosterol/metabolism , Food Technology/methods , Glucosamine/analysis , Glucosamine/metabolism , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Patents as Topic , Proteins/analysis , Proteins/metabolism
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