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

The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis

Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL

ESCP Guidance on use of mesh in pelvis in colorectal surgery

This is a comprehensive and rigorous review of currently available data on the use of mesh in the pelvis in colorectal surgery. This guideline outlines the limitations of available data and the challenges of interpretation, followed by best possible recommendations

Summary of Materials and Methods.

<p>Summary of Materials and Methods.</p

Boxplots representing the median binding of each isolate and reference strain to mucin from the UC colon compared to controls.

<p>Direct comparison of the median binding of isolates of <i>A</i>. <i>mucinihpila</i> (a). Direct comparison of median binding of isolates of <i>Desulfovibrio</i> spp. (b).</p

Boxplots illustrating the binding of clinical isolates and reference strains to mucin from different sources.

<p>Median binding of isolates of <i>A</i>. <i>muciniphila</i> to control mucin (a) Median binding of isolates of <i>A</i>. <i>muciniphila</i> to UC mucin (b) Median binding of isolates of <i>Desulfovibrio</i> spp. to control mucin (c) Median binding of isolates of <i>Desulfovibrio</i> spp. to UC mucin (d).</p

Median binding values of each isolate to mucin from controls and the UC colon and Kruskal-Wallis tests comparing the binding of clinical isolates to that of the reference strain for <i>A</i>. <i>muciniphila</i> and <i>Desulfovibrio</i> spp.

<p>Significant values are highlighted in bold text. FU corresponds to measure of bacterial binding in fluorescent units. IQR corresponds to inter quartile range.</p><p>Median binding values of each isolate to mucin from controls and the UC colon and Kruskal-Wallis tests comparing the binding of clinical isolates to that of the reference strain for <i>A</i>. <i>muciniphila</i> and <i>Desulfovibrio</i> spp.</p