Association of maternal Vitamin D status with glucose tolerance and caesarean section in a multi-ethnic Asian cohort: the growing up in Singapore towards healthy outcomes study

10.1371/journal.pone.0142239PLoS ONE10111-16GUSTO (Growing up towards Healthy Outcomes

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

Cross-sectional and prospective associations between children's 24-hour time use and their health-related quality of life: a compositional isotemporal substitution approach

Background: promoting active, balanced lifestyles among children may be an important approach to optimising their health-related quality of life (HRQoL). However, the relationships between children's movement behaviours and HRQoL remain unclear.Methods: we examined the associations between movement behaviours (sleep, inactivity, light and moderate-to-vigorous intensity physical activity) assessed using accelerometers at ages 8 and 10 years and self-reported HRQoL scores (overall, and physical and emotional well-being, self-esteem, relationship with family and friends, and school functioning domains) at age 10 years among 370 children in a local birth cohort using compositional isotemporal substitution techniques.Findings: cross-sectionally, light and moderate-to-vigorous intensity physical activities were associated with better self-esteem (β = 15.94 [2.71, 29.18]) and relationship with friends (β = 10.28 [3.81, 16.74]) scores respectively. Prospectively, inactivity was associated with lower overall HRQoL (β = −10.00 [−19.13, −0.87]), relationship with friends (β = −16.41 [−31.60, −1.23]) and school functioning (β = −15.30 [−29.16, −1.44]) scores, while sleep showed a positive trend with overall HRQoL (β = 10.76 [−1.09, 22.61]) and school functioning (β = 17.12 [−0.87, 35.10]) scores. Children's movement behaviours were not associated with their physical and emotional well-being, or relationship with family scores. The isotemporal substitution analyses suggest that increasing time spent in physical activity and/or sleep at the expense of inactivity may benefit children's HRQoL.Interpretation: our findings suggest that sleep and physical activity may be associated with better HRQoL, with the inverse for inactivity. However, the relationship between children's movement behaviours and HRQoL is complex and warrants further research.Funding: Singapore National Research Foundation, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research