The majority of naturally occurring proteins have evolved to function under mild conditions inside the living organisms. One of the critical obstacles for the use of proteins in biotechnological applications is their insufficient stability at elevated temperatures or in the presence of salts. Since experimental screening for stabilizing mutations is typically laborious and expensive, in silico predictors are often used for narrowing down the mutational landscape. The recent advances in machine learning and artificial intelligence further facilitate the development of such computational tools. However, the accuracy of these predictors strongly depends on the quality and amount of data used for training and testing, which have often been reported as the current bottleneck of the approach. To address this problem, we present a novel database of experimental thermostability data for single-point mutants FireProtDB. The database combines the published datasets, data extracted manually from the recent literature, and the data collected in our laboratory. Its user interface is designed to facilitate both types of the expected use: (i) the interactive explorations of individual entries on the level of a protein or mutation and (ii) the construction of highly customized and machine learning-friendly datasets using advanced searching and filtering. The database is freely available at https://loschmidt.chemi.muni.cz/fireprotdb.
BackgroundPrevious therapy with anthracyclines (ANT) and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT) represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers - high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and to identify patients at risk of developing clinical cardiotoxicity.Patients and methodsThirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI) or combination of chemotherapy with TBI. Twenty-nine (78,3%) patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography.ResultsThe changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (P < 0,01 v.s. P < 0,01). Persistent elevations of NT-proBNP and hs-cTnT simultaneously for a period exceeding 14 days after HSCT were found in 29,7% patients. Serum concentrations of cardiomarkers were significantly elevated in ANT group compared to non-ANT group. These observations were underscored by the echocardiographic studies which did reveal significant changes in systolic and diastolic parameters. Five of 37 (13,5%) patients developed clinical manifestation of cardiotoxicity.ConclusionsElevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up.
RVSD is an independent predictor of all-cause mortality in HFPEF. Patients with HFPEF and RVSD had significantly higher one-year all-cause and cardiovascular mortality than those with normal RV function.
The long-term prognosis of patients after haematopoietic stem cell transplantation (HSCT) has greatly improved. Cardiac complications represent unresolved and potentially life-threatening conditions in these patients. We prospectively examined 37 consecutive patients with a median age of 28 years who underwent allogeneic HSCT. Biomarkers of cardiac injury were measured serially before the conditioning regimen, the first day after HSCT and then 14, 30, 90 and 180 days after HSCT. Echocardiography was performed before and 1 month after HSCT. Eleven patients (30%) had persistently increased NT-proBNP values, 14 patients (38%) had only transient elevations and 12 (32%) had no changes in NT-proBNP concentrations for a period exceeding 14 days after HSCT. Elevated NT-proBNP values at day 14 after HSCT remained an independent predictor of cardiotoxicity during the first 6 months after HSCT (P < 0.01). Patients with persistent elevations in NT-proBNP also had significant elevations in hs-cTnT concentrations (P < 0.01). Only patients with persistently increased NT-proBNP had a significant worsening in systolic and some diastolic echocardiographic parameters, and we observed in this group the highest values of both cardiomarkers during the 6-month period. Forty-five percent of these patients developed clinical manifestation of cardiotoxicity. Elevations in NT-proBNP concentrations at day 14 after HSCT can predict patients at risk of developing cardiac events during the first 6 months after HSCT. Simultaneous elevations of both cardiomarkers (NT-proBNP and hs-cTnT) persisting 14 days after HSCT had a sensitivity of 83% and a specificity of 80.69%.
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