UPS Freight Less-than-Truckload (LTL) transportation services are offered by TFI International Inc., its affiliates or divisions (including without limitation TForce Freight), which are not affiliated with United Parcel Service, Inc. ATLAS.ti allows you to focus on the data itself.Tracking UPS - United States. Sophisticated and complete tools help you organize, integrate, and manage your information in a creative and systematic way. ATLAS.ti Mac is a powerful qualitative data Analysis Mac cracked app is a powerful workbench for qualitative analysis of large-capacity text, , audio and video data.This study reports an integrative, network-based deep-learning methodology to identify repurposable drugs for COVID-19 (termed CoV-KGE). Drug repurposing offers a promising route for the development of prevention and treatment strategies for COVID-19. However, there is currently a lack of proven effective medications against COVID-19.
Save Hu Atlas.Ti Mac Is A(7−9) We recently demonstrated that network-based methodologies leveraging the relationship between drug targets and diseases can serve as a useful tool for the efficient screening of potentially new indications of FDA-approved drugs with well-established pharmacokinetic/pharmacodynamic, safety, and tolerability profiles. (6) The systematic identification of virus–host protein–protein interactions (PPIs) offers an effective way toward the elucidation of the mechanisms of viral infection furthermore, targeting the cellular virus–host interactome offers a promising strategy for the development of effective drug repurposing for COVID-19, as demonstrated in previous studies. SARS-CoV-2 replication and infection depend on the host cellular factors (including angiotensin-converting enzyme 2 (ACE2)) for entry into cells. Bundle function in the Tools.In a randomized, controlled, open-label trial, (5) lopinavir and ritonavir combination therapy did not show a clinical benefit compared with standard care for hospitalized adult patients with severe COVID-19, limiting the traditional antiviral treatment for COVID-19. Whereas this study by no means recommends specific drugs, it demonstrates a powerful deep-learning methodology to prioritize existing drugs for further investigation, which holds the potential to accelerate therapeutic development for COVID-19.ATLAS.ti takes away the job of managing data, leaving the analysis job for the researchers: makes the research work relatively simpler Training Modules (with book handout): General principles of Qualitative Research Basics of Lit review Intro to ATLAS.ti Create project in ATLAS.ti (HU) Functions (codes, quotes, memos)The process of saving and moving the HU and data is slightly more difficult to manage than in other packages, although the Copy. Using Amazon’s AWS computing resources and a network-based, deep-learning framework, we identified 41 repurposable drugs (including dexamethasone, indomethacin, niclosamide, and toremifene) whose therapeutic associations with COVID-19 were validated by transcriptomic and proteomics data in SARS-CoV-2-infected human cells and data from ongoing clinical trials. For these drugs, we included in the KG relationships corresponding to the drug–drug interactions and the drug side-effects, drug anatomical therapeutic chemical (ATC) codes, drug mechanisms of action, drug pharmacodynamics, and drug-toxicity associations. Second, from the DrugBank database, (19) we selected the drugs whose molecular mass is >230 Da and also exist in GNBR, resulting in 3481 FDA-approved and clinically investigational drugs. (19) First, from GNBR, we included in the KG relations corresponding to drug–gene interactions, gene–gene interactions, drug–disease associations, and gene–disease associations. Four differential expression data sets were collected, including two transcriptome data sets from SARS-CoV patients’ peripheral blood (21) (GSE1739) and Calu-3 cells (22) (GSE33267), one transcriptome data set of Calu-3 cells infected by MERS-CoV (23) (GSE122876), and one proteome data set of human Caco-2 cells infected with SARS-CoV-2. The goal of the gene set enrichment analysis was to identify drugs that can reverse the cellular changes (transcriptome or proteome levels) that result from virus infection. The resulting KG contains four types of entities (drug, gene, disease, and drug side information), 39 types of relationships ( Table S1), 145 179 nodes, and 15 018 067 edges ( Table S2).Gene set enrichment analysis was performed to further validate the predicted drug candidates from CoV-KGE. (9) Fourth, we treated the COVID-19 context by assembling known genes/proteins associated with CoVs (including SARS-CoV and MERS-CoV) as a comprehensive node of CoVs and rewired the connections (edges) from genes and drugs. The number of significantly enriched data sets is used as the final result for a certain drug.We further validated the top candidate drugs using an enrichment analysis of drug–gene signatures and SARS-CoV-induced transcriptomics and proteomics data in human cell lines (cf. ES > 0 and P < 0.05 are considered significantly enriched. In each repeat, the same number of up- and down- expressed genes as the CoV signature data set was randomly generated. Permutation tests are repeated 100 times to quantify the significance of the ES score. Next, ES up/down is set to a up/down if a up/down > b up/down and is set to − b up/down if b up/down > a up/down. V( j) denotes the rank of j, where 1 ≤ V( j) ≤ r, with r being the total number of genes (12 849) from the CMap database. (29,30)Given the well-described lung pathophysiological characteristics and immune responses (cytokine storms) of severe COVID-19 patients, drugs that dampen the immune responses may offer effective treatment approaches for COVID-19. We excluded chloroquine and hydroxychloroquine from our ongoing clinical trial list based on recently controversial reports. Among the 41 candidate drugs, 9 drugs are or have been under clinical trials for COVID-19, including thalidomide, methylprednisolone, ribavirin, umifenovir, tetrandrine, suramin, dexamethasone, lopinavir, and azithromycin ( Figure 3A and Table 1). In total, we obtained 41 repositioned drug candidates ( Table 1) using subject-matter expertise based on a combination of factors: (i) the strength of the CoV-KGE predicted score, (ii) the availability of clinical evidence from ongoing COVID-19 trials, and (iii) the availability and strength of enrichment analyses from SARS-CoV-1/2-affected human cell lines. Melatonin has various antiviral activities by suppressing multiple inflammatory pathways (35,36) (i.e., IL6 and IL-1β) these inflammatory effects are directly relevant given the well-described lung pathophysiological characteristics of severe COVID-19 patients. (34) Melatonin plays a key role in the regulation of the human circadian rhythm that alters the translation of thousands of genes, including melatonin-mediated anti-inflammatory and immune-related effects for COVID-19. (34) Importantly, a preliminary in vivo observation showed that oral indomethacin (1 mg/kg body weight daily) reduced the recovery time of SARS-CoV-2-infected dogs. (33) Indomethacin has been reported to have antiviral properties, including SARS-CoV-1 (33) and SARS-CoV-2. Indomethacin, an approved cyclooxygenase (COX) inhibitor, has been widely used for its potent anti-inflammatory and analgesic properties. Download for adobe acrobat pro 2017 for mac installerToremifene, the first generation of the nonsteroidal SERM, was reported to block various viral infections at low micromolar concentration, including Ebola virus, (42,43) MRES-CoV, (44) SARS-CoV-1, (45) and SARS-CoV-2 (46) ( Figure 3B). (41) Several SERMs, including clomifene, bazedoxifene, and toremifene, are identified as promising candidate drugs for COVID-19 ( Figure 3A and Table 1). (37)An overexpression of the estrogen receptor has played a crucial role in inhibiting viral replication and infection. (37) In addition, exogenous melatonin administration may be of particular benefit to older patients given the aging-related reduction of endogenous melatonin levels and the vulnerability of older individuals to the lethality of SARS-CoV-2. (42) The underlying antiviral mechanisms of SARS-CoV-1 and SARS-CoV-2 for toremifene remain unclear and are currently being investigated.
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