Abstract

In the field of clinical research, it is crucial to determine the safety and efficacy of current drugs and further accelerate the discovery of new active compounds. The traditional methods performed expensive laboratory tests. These methods are very costly and require a long time. However, bioinformatics can greatly facilitate the clinical research for the above purposes, providing the prediction of drug toxicity and activity in new diseases and evaluating the validity of active compounds discovered in clinical trials. This can be achieved through the availability of bioinformatics tools and methods of computer virtual screening (VS) that allow the test all the necessary hypotheses before doing the clinical trials, such as structural docking using the BINDSURF program. However, the accuracy of most VS methods is severely restricted due to constraints in the affinity or scoring functions describing biomolecular interactions, and even today these uncertainties are not fully known. In this paper we address this problem by proposing a new approach in which neural networks are trained with information on databases of known compounds (target proteins and drugs), for further exploiting the method to improve the accuracy of VS BINDSURF predictions of affinity.

Abstract

xtabstractProlonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, butwhether this results fromthe increased duration of treatment or a higher cumulative dose remains unclear.We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo ( n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m2). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not bene fit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration. Copyrigh