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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

WHOLESALE MARKETING OPPORTUNITIES FOR OHIO VEGETABLE GROWERS

Marketing,

Caries treatment in a dental practice-based research network:movement toward stated evidence-based treatment

BACKGROUND: Practice-based research networks (PBRNs) provide a venue to foster evidence-based care. We tested the hypothesis that a higher level of participation in a dental PBRN is associated with greater stated change toward evidence-based practice. METHODS: A total of 565 dental PBRN practitioner-investigators completed a baseline questionnaire entitled “Assessment of Caries Diagnosis and Treatment”; 405 of these also completed a follow-up questionnaire about treatment of caries and existing restorations. Certain questions (6 treatment scenarios) were repeated at follow-up a mean (S.D.) of 36.0 (3.8) months later. A total of 224 were “full participants” (enrolled in clinical studies and attended at least one network meeting); 181 were “partial participants” (did not meet “full” criteria). RESULTS: From 10% to 62% of practitioners were “surgically invasive” at baseline, depending on the clinical scenario. Stated treatment approach was significantly less-invasive at follow-up for 4 of 6 items. Change was greater among full participants and those with a more-invasive approach at baseline, with an overall pattern of movement away from the extremes. CONCLUSIONS: These results are consistent with a preliminary conclusion that network participation fostered movement of scientific evidence into routine practice. PBRNs may foster movement of evidence into everyday practice as practitioners become engaged in the scientific process

Rehabilitation and medical management of the adult with spina bifida

As the life expectancy of individuals with spina bifida increases, a lifelong need for management of many health issues in a rehabilitation setting has emerged in recent years. Physiatrists, in consultation with a variety of adult specialists, are particularly well suited to manage the common musculoskeletal, skin, bowel, bladder, renal, neurological, and other issues that arise in the adult population. This article reviews the last 20 yrs of literature pertinent to the rehabilitative care of this population, summarizes current evidence-based practice, and identifies key areas in which scientific evidence is lacking and future research is needed. Copyright © 2008 by Lippincott Williams & Wilkins