ThermoScan: Semi-automatic Identification of Protein Stability Data From PubMed

open3noThis work was supported by the PRIN project, “Integrative tools for defining the molecular basis of the diseases: Computational and Experimental methods for Protein Variant Interpretation” of the Ministero Istruzione, Università e Ricerca (201744NR8S).During the last years, the increasing number of DNA sequencing and protein mutagenesis studies has generated a large amount of variation data published in the biomedical literature. The collection of such data has been essential for the development and assessment of tools predicting the impact of protein variants at functional and structural levels. Nevertheless, the collection of manually curated data from literature is a highly time consuming and costly process that requires domain experts. In particular, the development of methods for predicting the effect of amino acid variants on protein stability relies on the thermodynamic data extracted from literature. In the past, such data were deposited in the ProTherm database, which however is no longer maintained since 2013. For facilitating the collection of protein thermodynamic data from literature, we developed the semi-automatic tool ThermoScan. ThermoScan is a text mining approach for the identification of relevant thermodynamic data on protein stability from full-text articles. The method relies on a regular expression searching for groups of words, including the most common conceptual words appearing in experimental studies on protein stability, several thermodynamic variables, and their units of measure. ThermoScan analyzes full-text articles from the PubMed Central Open Access subset and calculates an empiric score that allows the identification of manuscripts reporting thermodynamic data on protein stability. The method was optimized on a set of publications included in the ProTherm database, and tested on a new curated set of articles, manually selected for presence of thermodynamic data. The results show that ThermoScan returns accurate predictions and outperforms recently developed text-mining algorithms based on the analysis of publication abstracts. Availability: The ThermoScan server is freely accessible online at https://folding.biofold.org/thermoscan. The ThermoScan python code and the Google Chrome extension for submitting visualized PMC web pages to the ThermoScan server are available at https://github.com/biofold/ThermoScan.openTurina P.; Fariselli P.; Capriotti E.Turina P.; Fariselli P.; Capriotti E

Valve replacement in octogenarians: increased early mortality but good long-term result

Between January 1983 and December 1990, 20 patients aged 80 years or older underwent valvular surgery. The patients' ages varied from 80 to 87 years (mean, 82 ± 1.5 years). The indication for operation was aortic stenosis in 19 patients, and mitral insufficiency after previous mitral valve replacement with a bioprosthesis in one. There were 15 elective, two urgent, and three emergency operations. Four of these patients had aortic valve replacement plus coronary artery bypass grafting. Six patients (30%) had an uneventful hospital stay, and the other 14 (70%) experienced several post-operative complications. The operative mortality rate was 15± (three patients). All patients before operation were in NYHA (New York Heart Association) class III and IV and all survivors remained in NYHA class I or II. The survivors have been followed from 6 to 70 months (mean 20 ± 8 months). The actuarial survival rate at 1 and 5 years was 78.5% and 67%, respectively. Valvular replacement in octogenarians can be performed, despite the high rate of post-operative complications, with increased but acceptable mortality. Long-term results are goo

Dynamics of drug sustainability Mycobacterium tuberculosis in the Belgorod region for the period of 2008-2017

To assess and compare the structure and dynamics of Mycobacterium tuberculosis drug resistance to anti-tuberculosis drugs, including multiple and broad, in the Belgorod region in newly diagnosed patients and patients with relapses of tuberculosi

Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation

Background: Malignancy is generally considered a contraindication for cardiac transplantation, whereas secondary malignancy has been described under chronic immunosuppression. Patients and methods: We report here the frequency of malignancy encountered among the 495 patients evaluated at our cardiac transplant centre as well as the incidence and the course of post-transplant malignancy among 129 consecutive patients who underwent cardiac transplantation, with a subsequent minimum follow-up of 6 months. Results: A total of 10 out of 495 patients (2%) evaluated for heart transplantation presented with a history of previous malignancy: 3 of them underwent transplantation (2 survive, 1 died) whereas in the remaining 7 patients neoplasia was considered a contraindication for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths). Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 ± 15 months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3 solid tumors). No significant association was found between post-transplant malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine antihuman T-cell monoclonal antibodies (OKT3). Conclusions: These results confirm that pre-transplant malignancy is not an absolute contraindication for cardiac transplantation and that post-transplant follow-up must include careful monitoring of post-transplant malignanc

Limitations and challenges in protein stability prediction upon genome variations: towards future applications in precision medicine

Protein stability predictions are becoming essential in medicine to develop novel immunotherapeutic agents and for drug discovery. Despite the large number of computational approaches for predicting the protein stability upon mutation, there are still critical unsolved problems: 1) the limited number of thermodynamic measurements for proteins provided by current databases; 2) the large intrinsic variability of \u394\u394G values due to different experimental conditions; 3) biases in the development of predictive methods caused by ignoring the anti-symmetry of \u394\u394G values between mutant and native protein forms; 4) over-optimistic prediction performance, due to sequence similarity between proteins used in training and test datasets. Here, we review these issues, highlighting new challenges required to improve current tools and to achieve more reliable predictions. In addition, we provide a perspective of how these methods will be beneficial for designing novel precision medicine approaches for several genetic disorders caused by mutations, such as cancer and neurodegenerative diseases

Surgical treatment versus medical treatment in hypertrophic obstructive cardiomyopathy

Sixty-three patients operated upon for HOCM and 49 patients selected for non-surgical treatment have been followed-up for 15 years. Pre-operatively, surgical patients had a higher left ventricular outflow tract gradient at rest and, on the average, more severe symptoms than non-surgical patients. Septal myectomy relieved the pressure gradient and symptoms more consistently than long-term treatment with β-blockers or verapamil. Within an average observation time of 7½ years, there was late deterioration or death in almost half of the non-surgical patients but in less than one-quarter in the operated patients. The 10 year mortality rate was 80% in the surgical series and 71% in the non-surgical series. In operated patients, pre-operative symptomatic status was significantly related to early and late mortality. In medically treated patients, mortality was unrelated to symptoms; however, it was significantly lower in patients receiving long term treatment with β-blockers or verapamil. In conclusion, a high basal pressure gradient associated to limiting symptoms is a clear-cut indication for surgery. Other indications are more debatable. In medically treated patients, long-term administration of β-blockers or verapamil is beneficial even without symptoms as it appears to improve prognosi

Does exercise-induced myocardial ischaemia cause enhanced platelet activation and fibrin formation in patients with stable angina and severe coronary artery disease?

In this study, betathromboglobulin (BTG) and fibrinopeptide A (FPA) in peripheral venous blood were measured in 20 patients with stable angina pectoris before and immediately after exercise-induced myocardial ischaemia; in 5 of the 20 patients stable angina was associated with typical peripheral artery disease. A total of 10 patients with angiographically documented peripheral artery disease without angina and 10 normal volunteers were taken as control groups. BTG and FPA in the 15 patients with stable angina before exercise were 41±14 ng ml-1 and 2.3±09 ng ml-1 and were not statistically different from the values in normal controls; after exercise-induced myocardial ischaemia no significant increase occurred in these patients. Conversely, in the 5 patients with stable angina associated with peripheral artery disease BTG and FPA before exercise were 6l±10 ng ml-1 and 3.5±0.8 ng ml-1 and increased to 114±14 ng ml-1 (P<0.001) and 4.l±0.5 ng ml-1 (P<0.01): These results were similar to those found in the 10 patients with isolated peripheral artery disease. We conclude that BTG and FPA in peripheral venous blood in patients with stable angina are not elevated either at rest or after exercise-induced myocardial ischaemia. Elevated values of BTG and FPA in patients with stable angina may reflect a major interaction between blood and atherosclerotic vessel wall, suggesting the presence of associated atherosclerotic lesions in peripheral artery diseas

Acute traumatic aortic rupture: early stent-graft repair

Objective: Prospective evaluation of early stent-graft repair of acute traumatic aortic rupture. Methods: Twelve patients with acute traumatic aortic rupture of the descending aorta, out of a series of 337 endovascular aortic procedures, were treated by implantation of self-expanding stent-grafts. The procedures were performed within a mean post-injury time-period of 5±7 days (median: 1 day). The feasibility of stent-grafting was assessed by CT scanning and echography. Implantation was performed under local (n=6), or general anesthesia (n=6) if patients were already intubated (n=5) or required a common iliac artery access (n=1). Results: The immediate technical success rate was 100%. There were no post-procedure complications in all but one patient, who died 12 h postoperatively (8% mortality). Complete sealing of the aortic rupture in the remaining 11 patients was confirmed by postoperative CT scans. There were no intervention-related morbidity or mortality during the mean follow-up of 17 months. One patient with peri-graft leakage was successfully repaired with an additional stent-graft 12 months postoperatively. Conclusion: Non-delayed or early stent-grafting in acute traumatic rupture of the descending aorta is feasible. This technique seems to be a valuable option, in particular when associated lesions may interfere with the surgical outcome. Immediate post-procedural CT scanning and/or echography should be performed, in order to rule out residual leakag