Enhanced Molecular Dynamics Method to Efficiently Increase the Discrimination Capability of Computational Protein-Protein Docking

Protein-protein docking typically consists of the generation of putative binding conformations, which are subsequently ranked by fast heuristic scoring functions. The simplicity of these functions allows for computational efficiency but has severe repercussions on their discrimination capabilities. In this work, we show the effectiveness of suitable descriptors calculated along short scaled molecular dynamics runs in recognizing the nearest-native bound conformation among a set of putative structures generated by the HADDOCK tool for eight protein-protein systems

The use of chest ultrasonography in suspected cases of COVID-19 in the emergency department

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases. Patients & methods: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods. Results: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%. Conclusion: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19. The gold standard for diagnosis of COVID-19 is RT-PCR. During a pandemic emergency, it may be useful to identify suspect symptomatic patients who may safely be observed without undergoing testing for COVID-19. In this work, a simple model based on the findings of lung ultrasound, AST levels and fever showed an overall accuracy of 91% to predict the results of RT-PCR

Pandemic Drugs at Pandemic Speed: Infrastructure for Accelerating COVID-19 Drug Discovery with Hybrid Machine Learning- and Physics-based Simulations on High Performance Computers

The race to meet the challenges of the global pandemic has served as a reminder that the existing drug discovery process is expensive, inefficient and slow. There is a major bottleneck screening the vast number of potential small molecules to shortlist lead compounds for antiviral drug development. New opportunities to accelerate drug discovery lie at the interface between machine learning methods, in this case, developed for linear accelerators, and physics-based methods. The two in silico methods, each have their own advantages and limitations which, interestingly, complement each other. Here, we present an innovative infrastructural development that combines both approaches to accelerate drug discovery. The scale of the potential resulting workflow is such that it is dependent on supercomputing to achieve extremely high throughput. We have demonstrated the viability of this workflow for the study of inhibitors for four COVID-19 target proteins and our ability to perform the required large-scale calculations to identify lead antiviral compounds through repurposing on a variety of supercomputers

Comparison of videolaparoscopic versus open surgery for benign renal diseases in children

Introduction: Laparoscopic nephrectomy in children has become a reasonable alternative to open nephrectomy and has replaced open surgery for many renal diseases. The purpose of our study is to evaluate transperitoneal videolaparoscopic procedures in renal benign diseases in comparison to an open surgery approach. Patients and methods: 34 children aged between 17 days and 15 years old (mean 6.14) were divided into two groups in order to be submitted to nephrectomy. The first one underwent transperitoneal videolaparoscopic nephrectomy and was composed by 21 patients aged from 2 months to 15 years (mean 7.42), from which 12 were females and 9 males. The second group was submitted to open nephrectomy and was composed by 13 patients aged from 17 days to 11 years (mean 3.91), 6 females and 7 males. The groups were compared regarding anesthesic time, operative time, length of hospital stay, postoperative pain and time of reintroduction of oral intake. Short and long term complications were also evaluated. Statistical analysis was performed by Student t-test with the level of significance set at P < 0.05. The study was previously approved by the Committee on Ethics in Research of our institution. Results: Significant statistical difference was observed only for the variable length of hospital stay. No laparoscopy group case was converted to open surgery. There was no immediate or late complication. Blood loss was negligible and no transfusion was required. Conclusions: In our experience, transperitoneal videolaparoscopic nephrectomy has similar results to open nephrectomy, except for time of hospitalization. (C) 2009 AEU. Published by Elsevier Espana, S.L. All rights reserved