AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

There is no benefit in the use of postnatal intravenous immunoglobulin for the prevention of relapses of multiple sclerosis: findings from a systematic review and meta-analysis

ABSTRACT Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disease of the central nervous system. Since MS affects mostly fertile women, pregnancy issues often arise in daily practice. The present study assessed the use of postpartum intravenous immunoglobulin (IVIG) in MS. Methods The authors individually searched for records using PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, and Google Scholar, using the terms “multiple sclerosis” OR “MS” AND “pregnancy” OR “gestation” OR “partum” OR “post-partum” OR “puerperium” AND “immunoglobulin”. Results The initial search returned 321 papers. There were 11 eligible articles selected for the review. In total, 380 patients had received post-natal IVIG to reduce the number of postpartum relapses. The unadjusted number needed to treat was 6.3 for the quantitative and 5.8 for the qualitative analyses. Conclusion The therapeutic effect of IVIG for prevention of postnatal relapses in MS could not clearly be established in this meta-analysis

Strategies for replacing non-invasive brain stimulation sessions: recommendations for designing neurostimulation clinical trials

<p><b>Introduction</b>: Despite the potential impact of missed visits on the outcomes of neuromodulation treatments, it is not clear how this issue has been addressed in clinical trials. Given this gap in the literature, we reviewed articles on non-invasive brain stimulation in participants with depression or chronic pain, and investigated how missed visits were handled.</p> <p><b>Areas covered</b>: We performed a search on PUBMED/MEDLINE using the keywords: ‘tDCS’, ‘transcranial direct current stimulation’, ‘transcranial magnetic stimulation’, ‘depression’, and ‘pain’. We included studies with a minimum of five participants who were diagnosed with depression or chronic pain, who underwent a minimum of five tDCS or TMS sessions. A total of 181 studies matched our inclusion criteria, 112 on depression and 69 on chronic pain. Of these, only fifteen (8%) articles reported or had a protocol addressing missed visits. This review demonstrates that, in most of the trials, there is no reported plan to handle missed visits.</p> <p><b>Expert commentary</b>: Based on our findings and previous studies, we developed suggestions on how to handle missed visits in neuromodulation protocols. A maximum of 20% of missing sessions should be allowed before excluding a patient and these sessions should be replaced at the end of the stimulation period.</p