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

Temporal associations between disordered eating and nonsuicidal self-injury: Examining symptom overlap over one year

Disordered eating (DE) and nonsuicidal self-injury (NSSI) commonly co-occur. This study compared several models of the longitudinal relationship between DE and NSSI, including concurrent and prospective models, and examined the possible moderating roles of self-objectification, impulsivity, and emotion dysregulation in these relationships. Individuals with NSSI (N=197) recruited from online forums completed measures of NSSI and DE every 3 months for 1 year. We tested the associations between NSSI and DE using hierarchical linear models. Results supported a concurrent relationship, wherein frequency of NSSI positively covaried with concurrent DE severity. Body surveillance moderated the concurrent relationship between NSSI and DE. Individuals who engaged in more body surveillance endorsed high levels of DE pathology, whereas those lower in body surveillance engaged in more frequent NSSI only at higher levels of DE. In addition, whereas DE did not prospectively predict NSSI, frequency of NSSI predicted more severe DE 3 months later. The prospective relationship between DE and later NSSI was moderated by emotion dysregulation, such that highly dysregulated individuals had a stronger relationship between DE and later NSSI, whereas this relationship was not significant among individuals low in emotion dysregulation. These findings add valuable information regarding the co-occurrence of self-damaging behaviors.status: publishe

Geographic Information System-based Screening for TB, HIV, and Syphilis (GIS-THIS): A Cross-Sectional Study

Abstract Objective: To determine the feasibility and case detection rate of a geographic information systems (GIS)-based integrated community screening strategy for tuberculosis, syphilis, and human immunodeficiency virus (HIV). Design: Prospective cross-sectional study of all participants presenting to geographic hot spot screenings in Wake County, North Carolina. Methods: The residences of tuberculosis, HIV, and syphilis cases incident between 1/1/05-12/31/07 were mapped. Areas with high densities of all 3 diseases were designated ''hot spots.'' Combined screening for tuberculosis, HIV, and syphilis were conducted at the hot spots; participants with positive tests were referred to the health department. Results and Conclusions: Participants (N = 247) reported high-risk characteristics: 67% previously incarcerated, 40% had lived in a homeless shelter, and 29% had a history of crack cocaine use. However, 34% reported never having been tested for HIV, and 41% did not recall prior tuberculin skin testing. Screening identified 3% (8/240) of participants with HIV infection, 1% (3/239) with untreated syphilis, and 15% (36/234) with latent tuberculosis infection. Of the eight persons with HIV, one was newly diagnosed and co-infected with latent tuberculosis; he was treated for latent TB and linked to an HIV provider. Two other HIV-positive persons had fallen out of care, and as a result of the study were linked back into HIV clinics. Of 27 persons with latent tuberculosis offered therapy, nine initiated and three completed treatment. GIS-based screening can effectively penetrate populations with high disease burden and poor healthcare access. Linkage to care remains challenging and will require creative interventions to impact morbidity

Sociodemographic Characteristics of General Population in Study Areas, Wake County, and North Carolina.

*<p>Source for Density Areas: ESRI Business Analyst, Census 2010 Summary Profile.</p>¥<p>Source for Wake County: <a href="http://www.wakegov.com/NR/rdonlyres/A51B919D-A7BC-48AC-92AC-2EF6FCEE60DD/0/2010CensusWakeCountyGeneralProfile.pdf" target="_blank">http://www.wakegov.com/NR/rdonlyres/A51B919D-A7BC-48AC-92AC-2EF6FCEE60DD/0/2010CensusWakeCountyGeneralProfile.pdf</a>.</p>£<p>Source for North Carolina: <a href="http://factfinder2.census.gov/faces/tableservices/jsf/pages/productview.xhtml?pid=DEC_10_DP_DPDP1&prodType=table" target="_blank">http://factfinder2.census.gov/faces/tableservices/jsf/pages/productview.xhtml?pid=DEC_10_DP_DPDP1&prodType=table</a>.</p

HIV, Syphilis and Active Tuberculosis Cases, 2005–2007.

<p>Based on public health surveillance data from January 2005 through December 2007, disease-specific cases were geocoded, including 665 HIV cases, 150 active TB cases, and 155 syphilis cases, with a match rate of 93%. An overlay map with data for all three diseases was used to identify two high-density “hot spots” (outlined).</p

Measured Prevalence of HIV, Latent Tuberculosis, and Syphilis in Study Group Compared to Health Department Clinic Population.

<p>Measured Prevalence of HIV, Latent Tuberculosis, and Syphilis in Study Group Compared to Health Department Clinic Population.</p