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Objective: Pharmaceutical documents such as the common technical document, package inserts (PIs), and interview forms (IFs) are available at the website of the Pharmaceuticals and Medical Devices Agency. However, because these documents were created with an emphasis on human readability in paper form, it is difficult to use the information included and interoperate these documents with computers. Using IFs, we will investigate how to structure pharmaceutical documents in the AI era to achieve both human and machine readability.Design/Methods: The IFs of arbitrary selected ten drugs were structured into Resource Description Framework (RDF) according to the Drug Interview Form Description Guidelines 2018 (updated version in 2019). The data were manually extracted from the IFs and entered into a spreadsheet before being converted to RDF by a written script. The PIs were converted to RDF in addition to the IFs. To examine the linkage with external databases, IDs in ChEMBL, which is a manually curated database of bioactive molecules with drug-like properties, were embedded in the RDF.Results: We demonstrated that the conversion of IFs and PIs into RDF makes it possible to easily retrieve the corresponding part of the PIs cited in the IFs. Furthermore, we quickly obtained the relevant data from ChEMBL, demonstrating the feasibility of linking IFs with an external database. Our attempt to RDFization of IFs is expected to encourage the development of web applications for healthcare professionals and the development of datasets for AI development.Conclusion: We could easily interoperate IFs with other pharmaceutical documents and an external database by converting IFs into RDF following the description guidelines. However, problems such as how to deal with items that were not described in the description guidelines were indicated. We hope that discussions will grow based on this effort and that related industries will move toward accomplishing effective use of these documents.
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AO_SCPLOWBSTRACTC_SCPLOWThe severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a highly contagious virus that causes a severe respiratory disease known as Corona virus disease 2019 (COVID19). Indeed, COVID19 increases the risk of cardiovascular occlusive/thrombotic events and is linked to poor outcomes. The pathophysiological processes underlying COVID19-induced thrombosis are complex, and remain poorly understood. To this end, platelets play important roles in regulating our cardiovascular system, including via contributions to coagulation and inflammation. There is an ample of evidence that circulating platelets are activated in COVID19 patients, which is a primary driver of the thrombotic outcome observed in these patients. However, the comprehensive molecular basis of platelet activation in COVID19 disease remains elusive, which warrants more investigation. Hence, we employed gene co-expression network analysis combined with pathways enrichment analysis to further investigate the aforementioned issues. Our study revealed three important gene clusters/modules that were closely related to COVID19. Furthermore, enrichment analysis showed that these three modules were mostly related to platelet metabolism, protein translation, mitochondrial activity, and oxidative phosphorylation, as well as regulation of megakaryocyte differentiation, and apoptosis, suggesting a hyperactivation status of platelets in COVID19. We identified the three hub genes from each of three key modules according to their intramodular connectivity value ranking, namely: COPE, CDC37, CAPNS1, AURKAIP1, LAMTOR2, GABARAP MT-ND1, MT-ND5, and MTRNR2L12. Collectively, our results offer a new and interesting insight into platelet involvement in COVID19 disease at the molecular level, which might aid in defining new targets for treatment of COVID19-induced thrombosis. key pointsO_LICo-expression analysis of platelet RNAseq from COVID19 patients show distinct clusters of genes (modules) that are highly correlated to COVID19 disease. C_LIO_LIIdentifying these modules might help in understanding the mechanism of thrombosis in COVID19 patients C_LI
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Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of key determinants of COVID-19 severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2, and the ACE2 abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection and metabolic disorder in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity, clomipramine showed the best potency to inhibit SARS-CoV-2 spike glycoprotein pseudovirus-stimulated ACE2 internalization. Indeed, SARS-CoV-2 infection to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19.