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In simulation studies and analysis of real data from the genotype-tissue expression (GTEx) project, we compared and evaluated the performance of RobNorm against other normalization methods. We found that the RobNorm approach exhibits the greatest reduction in systematic bias while maintaining across-tissue variation, especially for datasets from highly heterogeneous samples. https//github.com/mwgrassgreen/RobNorm. https//github.com/mwgrassgreen/RobNorm. The detection of SARS-CoV-2 RNA by real-time polymerase chain reaction (PCR) in respiratory samples collected from persons recovered from COVID-19 does not necessarily indicate shedding of infective virions. By contrast, the isolation of SARS-CoV-2 using cell-based culture likely indicates infectivity, but there are limited data on the correlation between SARS-CoV-2 culture and PCR. One hundred and ninety-five patients with varying severity of COVID-19 were tested (outpatients [n=178]), inpatients [n=12] and critically unwell patients admitted to the intensive care unit [ICU; n=5]). SARS-CoV-2 PCR positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was observed, PCR was performed on day four to confirm absence of virus replication. https://www.selleckchem.com/products/selonsertib-gs-4997.html Cycle threshold (Ct) of the day four PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined where Ctsample - Ctculture was ≥3. Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was only successfully isolated from samples with Ctsample ≤32, including in 28/181 (15%), 19/42 (45%) and 9/11 samples (82%) collected from outpatients, inpatients, and ICU patients, respectively. The mean duration from symptom onset to culture positivity was 4.5 days (range 0-18). SARS-CoV-2 was significantly more likely to be isolated from samples collected from inpatients (p<0∙001) and ICU patients (p<0∙0001) compared with outpatients respectively, and in samples with lower Ctsample. SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols. SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols. Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial. We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP Cyclohydrolase -1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80 mg once daily) on these parameters, blood biomarkers and the postoperative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB.CPB and reperfusion ledsurgery. In patients undergoing on-pump cardiac surgery, we show that perioperative administration of statins prevents myocardial nitroso-redox imbalance after reperfusion without affecting atrial refractoriness or perioperative myocardial injury. These findings suggest that targeting myocardial nitroso-redox imbalance would be unlikely to prevent postoperative complications in patients undergoing on-pump cardiac surgery. Neural methods to extract drug-drug interactions (DDIs) from literature require a large number of annotations. In this study, we propose a novel method to effectively utilize external drug database information as well as information from large-scale plain text for DDI extraction. Specifically, we focus on drug description and molecular structure information as the drug database information. We evaluated our approach on the DDIExtraction 2013 shared task data set. We obtained the following results. First, large-scale raw text information can greatly improve the performance of extracting DDIs when combined with the existing model and it shows the state-of-the-art performance. Second, each of drug description and molecular structure information is helpful to further improve the DDI performance for some specific DDI types. Finally, the simultaneous use of the drug description and molecular structure information can significantly improve the performance on all the DDI types. We showed that the plain text, the drug description information, and molecular structure information are complementary and their effective combination are essential for the improvement. https//github.com/tticoin/DESC_MOL-DDIE. https//github.com/tticoin/DESC_MOL-DDIE. Polypeptides are exposed to changing environmental conditions that modulate their intrinsic aggregation propensities. Intrinsically disordered proteins (IDPs) constitutively expose their aggregation determinants to the solvent, thus being especially sensitive to its fluctuations. However, solvent conditions are often disregarded in computational aggregation predictors. We recently developed a phenomenological model to predict IDPs' solubility as a function of the solution pH, which is based on the assumption that both protein lipophilicity and charge depend on this parameter. The model anticipated solubility changes in different IDPs accurately. In this application note, we present SolupHred, a web-based interface that implements the aforementioned theoretical framework into a predictive tool able to compute IDPs aggregation propensities as a function of pH. SolupHred is the first dedicated software for the prediction of pH-dependent protein aggregation. The SolupHred web server is freely available for academic users at https//ppmclab.pythonanywhere.com/SolupHred. It is platform-independent and does not require previous registration. Supplementary data are available at Bioinformatics online. Supplementary data are available at Bioinformatics online.
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