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

I Diretrizes do Grupo de Estudos em Cardiogeriatria da Sociedade Brasileira de Cardiologia

O idoso apresenta características próprias na manifestação das doenças, na resposta à terapêutica e no efeito colateral dos medicamentos. Constitui um grupo de maior risco para o aparecimento das doenças degenerativas, em geral, e cardiovasculares, em particular, além de apresentar maior número de comorbidades

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Novas pesquisas sobre as plantas hospedeiras do nematóide do cafeeiro, Meloidogyne exigua Goeldi, 1887

Foram realizadas provas para conhecer a reação de 54 culturas e 34 ervas más ao nematóide Meloidogyne exigua. Nenhuma planta se revelou sensível ao parasito, apresentando-se atacadas apenas as variedades de Coffea arabica e um híbrido de C. arabica e C. excelsa.Tests were performed in order to evaluate the reaction of 54 crops and 34 weed species to M. exigua. None revealed to be susceptible to this parasite. Several of the species were attacked by other root-knot nematodes, to which they are well known hosts

Parsing the differences between LHON affected

We aim to demonstrate that "purely genetic" and "tobacco-triggered" LHON may be different diseases

Obtenção minimamente invasiva de veia safena para cirurgia de revascularização do miocárdio

OBJETIVO: Analisar, comparativamente, a obtenção minimamente invasiva com o uso do MINI-HARVEST® e com instrumental tradicional adaptado. MÉTODO: de junho de 1996 a janeiro de 1999, 63 pacientes submetidos à cirurgia de revascularização do miocárdio tiveram suas veias safenas retiradas segundo técnica minimamente invasiva. Nos 30 primeiros pacientes da série utilizou-se método de visão direta com auxílio de dois afastadores de Langenbeck, e nos 33 restantes utilizou-se o MINI-HARVEST®. RESULTADOS: A idade média dos pacientes era de 61 ± 8,75 anos, sendo 52 homens e 11 mulheres. Quarenta e cinco pacientes eram diabéticos, 45 apresentavam sobrepeso/obesidade, 25 eram tabagistas ativos, 32 apresentavam história pregressa de infarto do miocárdio. O tempo médio de retirada da veia safena com afastadores Langenbeck foi de 34,2 ± 8,14 minutos e com o MINI-HARVEST® de 39,20 ± 9,12 minutos. A extensão de veia retirada foi similar nos dois grupos, variando de 10 a 30 cm. Houve uma deiscência superficial no grupo com afastadores de Langenbeck. Houve necessidade de reversão para método tradicional de retirada em dois casos do grupo MINI-HARVEST® e um do grupo Langenbeck. A incidência de infarto transoperatório foi 4,5% (três) no grupo Langenbeck e 3,1%(dois) no grupo MINI-HARVEST®. CONCLUSÕES: Podemos concluir que o método de obtenção de veia safena minimamente invasivo sob visão direta é efetivo e seguro, tanto com o uso de instrumentos tradicionais adaptados para este fim, como com afastadores especialmente constituídos, ressaltando-se que o MINI-HARVEST® dispensa a presença de um auxiliar.OBJECTIVE: To comparatively analyze minimally invasive procurement of saphenous veins using Mini-Harvest® system and a technique using adapted traditional instruments. METHOD: From June 1996 to January 1999, 63 patients who were submitted to Coronary Artery Bypass Grafting Surgery had their saphenous veins resected using minimally invasive techniques. In the first 30 patients of the series, a direct visualization method employing two Langenbeck's retractors was utilized and for the 33 remaining patients the Mini-Harvest® technique was utilized. RESULTS: The mean age of the patients was 61 ± 8.75 years old. Fifty-two patients were male and 11 female. Forty-five patients were diabetics, 45 were overweight or obese, 25 were smokers and 32 presented history of myocardial infarction. The mean time to resect the saphenous vein using the Langenbeck's retractors was 34.2 ± 8.14 minutes and using the Mini-Harvest® it was 39.20 ± 9.12 minutes. The lenghts of the extracted veins were similar in both groups, varying between 10 and 30 cm. There was one case of superficial dehiscence in the Langenbeck group. With two patients in the Mini-Harvest® group and one in Langenbeck's group it was necessary to revert to the traditional method of procurement. The incidence of tran-soperative infarction was 4.5% (three patients) in Langenbeck's group and 3.1% (two patients) in the Mini-Harvest® group. CONCLUSIONS: We can conclude that the minimally invasive procurement methods of the saphenous vein by direct visualization are effective and safe, both when employing adapted traditional instruments and using purpose-made retractors. We stress, however, that the Mini-Harvest® method does not require an assistant