Game on! A randomised controlled trial evaluation of playable technology in improving body satisfaction and negative affect among adolescents

Playables are mini-games used in digital advertising and may offer a novel and engaging avenue to improve young people’s well-being at scale. This randomised controlled trial evaluated the immediate impact and protective properties of a psychoeducational playable on adolescents’ body satisfaction and negative affect, and engagement in prosocial behaviours, relative to two active control conditions. Girls and boys aged 13–14 years (N = 6575) were randomised into one of three conditions: body image playable, body image social networking posts (i.e. static images of the body image playable messages; control 1) or an ocean conservation playable (control 2). Both body image micro-interventions significantly improved state body satisfaction and negative affect, relative to the oceanic playable. No condition buffered against the negative effects associated with viewing idealised media images. Developing playables to counteract the potentially harmful effects associated with surrounding digital environments is a promising avenue for mental health

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Wild jackdaws learn to tolerate juveniles to exploit new foraging opportunities

Social tolerance can enhance access to resources and is thought to be crucial in facilitating the evolution of cooperation, social cognition and culture, but it is unknown whether animals can optimize their social tolerance through learning. We presented wild jackdaws (Corvus monedula) with a novel social information problem using automated feeders. Juveniles could always feed (simulating a situation where juveniles were sources of information about a new resource) but adults could only access food if they inhibited their tendency to displace juveniles and instead showed tolerance by occupying an adjacent feeder perch. Accordingly, adults learned to tolerate juveniles, with some evidence they generalized across juveniles as a cohort. The ability to learn to tolerate sources of valuable information, and generalize across cohorts of informed individuals, may facilitate adaptive responses in the face of environmental change and help to explain the success of jackdaws in human-dominated environments

Game on! A randomised controlled trial evaluation of playable technology in improving body satisfaction and negative affect among adolescents

Playables are mini-games used in digital advertising and may offer a novel and engaging avenue to improve young people’s well-being at scale. This randomised controlled trial evaluated the immediate impact and protective properties of a psychoeducational playable on adolescents’ body satisfaction and negative affect, and engagement in prosocial behaviours, relative to two active control conditions. Girls and boys aged 13–14 years ( N = 6575) were randomised into one of three conditions: body image playable, body image social networking posts (i.e. static images of the body image playable messages; control 1) or an ocean conservation playable (control 2). Both body image micro-interventions significantly improved state body satisfaction and negative affect, relative to the oceanic playable. No condition buffered against the negative effects associated with viewing idealised media images. Developing playables to counteract the potentially harmful effects associated with surrounding digital environments is a promising avenue for mental health. </jats:p

Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors

AbstractThe COVID-19 pandemic was a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Pandemics could be prevented in principle by accessible, easily deployable broad-spectrum oral antivirals. Here we report the results of theCOVID Moonshot, a fully open-science, crowd sourced, structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical series that is differentiated from current Mpro inhibitors in that it maintains a new non-covalent, non-peptidic scaffold with nanomolar potency. Our approach leveraged crowdsourcing, high-throughput structural biology, machine learning, and exascale molecular simulations and high-throughput chemistry. In the process, we generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (&gt;18,000 designs), crystallographic data (&gt;840 ligand-bound X-ray structures), assay data (&gt;10,000 measurements), and synthesized molecules (&gt;2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.</jats:p

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery