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A unique approach to bioactivity and chemical data curation coupled with random forest analyses has led to a series of target-specific and cross-validated predictive feature fingerprints (PFF) that have high predictability across multiple therapeutic targets and disease stages involved in the severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2)-induced COVID-19 pandemic, which include plasma kallikrein, human immunodeficiency virus (HIV)-protease, nonstructural protein (NSP)5, NSP12, Janus kinase (JAK) family, and AT-1. The approach was highly accurate in determining the matched target for the different compound sets and suggests that the models could be used for virtual screening of target-specific compound libraries. The curation-modeling process was successfully applied to a SARS-CoV-2 phenotypic screen and could be used for predictive bioactivity estimation and prioritization for clinical trial selection; virtual screening of drug libraries for the repurposing of drug molecules; and analysis and direction of proprietary data sets.

A unique approach to bioactivity and chemical data curation coupled with Random forest analyses has led to a series of target-specific and cross-validated Predictive Feature Fingerprints (PFF) that have high predictability across multiple therapeutic targets and disease stages involved in the SARS-CoV-2 induced COVID-19 pandemic, which include plasma kallikrein, HIV protease, NSP5, NSP12, JAK family and AT-1. The approach was highly accurate in determining the matched target for the different compound sets and suggests that the models could be used for virtual screening of target specific compound libraries. The curation-modeling process was successfully applied to a SARS-CoV-2 phenotypic screen and could be used for predictive bioactivity estimation and prioritization for clinical trial selection, virtual screening of drug libraries for repurposing of drug molecules, and analysis and direction of proprietary datasets.

Background: Currently, hematologic neoplasms are diagnosed using a combination of methods, which require complex equipment and highly skilled clinical laboratory scientists and technicians - scarce resources. WGS and WTS could streamline this process and become a singular method. Interpretation of WGS and WTS data in a diagnostic setting is extremely challenging due to the breadth of data and its high-dimensional data types. AI will be mandatory to identify clinically meaningful genetic patterns and produce unbiased diagnosis. Aim: Compute leukemia diagnosis using AI methods with WGS and WTS data only, depicting relevant features for a decision and thus making its results comprehensible and transparent to humans. Methods: To train the model we used our cohort of 4,689 samples both with WGS (100x coverage, 2x151bp) and WTS (50 mio reads/sample, 2x101bp), along with our independent final routine diagnosis based on gold standard techniques (GST) and following WHO guidelines. Single nucleotide variants (SNV), structural variants (SV) and copy number alterations (CNA) from WGS data using a tumor w/o normal pipeline and gene fusions (GF) and gene expression (GE) from WTS were extracted. The cohort comprised of 30 different neoplasms and was severely imbalanced (n: 20 - 773). To test its performance another independent cohort which was not used during model creation (n=202, 22 entities) was selected. Results: We trained an ensemble of multi-class classifier using SageMaker (AWS, Seattle, WA) based on LGBM implementation of gradient boosted decision trees (Ke et al, 2017) in a one vs. rest architecture (1vRA). The model accuracy reached 85% overall on a 5-fold cross-validation (Fig 1a). Since neighboring disease types such as MGUS/MM, MDS-EB-2/AML/CMML are in some cases difficult to classify correctly using GST, we trained entity-specific classifiers operating independently. Rather than forcing a single predicted class to be predicted as overwhelmingly likely, this architecture accounts for ambiguous entities. In addition to reflecting biological similarity, the 1vRA resulted in improved probability calibration, so that cases with ambiguous leukemias are more easily identifiable by the distribution of predicted class probabilities and flagged for a human. Expected calibration error was only 3.8% for the 1vRA with entity-specific components, compared to 8.7% for a single LGBM model. Typically, AI methods are black boxes, making it hard for a medical professional to understand predictions, which results in low confidence and acceptance of such systems. Thus, we particularly focused on the transparency aspect of the model. We employed the SHAP library (Lundberg et al, 2017) to retrace the models output and gain insight into the features (i.e. which SNV, SV, GE etc.) predominantly driving classification results (e.g. LPL case Fig 1b). Fig. 1c illustrates the application of SHAP at the global cohort level for two individuals wrongly diagnosed with CML compared to CML correctly predicted cohort. By using a decision plot, we can observe which features are the most important contributors to the model's prediction. Fig 1c shows that predictions for CML are primarily driven by the BCR-ABL1 features, as expected. In our independent test cohort the following entities reached a very high concordance, such as AML (16/21) AUL (11/12), BCP-ALL (10/10), CML (13/13), HZL (8/8), MGUS (7/7), Multiple Myeloma (9/11), PNH (10/10), T-ALL (6/7). Other clear cut entities with correct high level predictions include BPDCN, FL, LPL, PPBL, NK-cell, HCL-variant and HGBL. In other entities such as T-NHL results were more heterogeneous, but this was also expressed in the probability scores given by the model. The first choice had a probability score of ~50%, exposing the correct diagnosis as the second likeliest one with ~40%. Test cohort included cases with mixed diagnostic characteristics, e.g. MDS/MPN-RS-T (4/11 correct, 4 predicted as MDS, and 3 as MPN). Conclusion: We present an AI tool to interpret WGS and WTS data aiming to predict the final diagnosis without any human input and high concordance to today's WHO classification. Due to the high data dimensionality of WGS and WTS data, an impossible feat for a human. The tool is exposed via a web application and visualizations make the automated decisions transparent and verifiable through humans paving a way for better adoption of WGS and WTS into a clinical routine setting. Figure 1 Figure 1. Disclosures Kern: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership.

In northern coastal Ecuador, water is routinely sold in 20 L reusable bottles for household consumption. These bottles are filled at central treatment facilities and distributed by private water companies. Similar bottled water markets are found in countries around the world. Commercially available bottled water offers an alternative source of drinking water in locations where piped infrastructure may be unsafe or non-existent. In this study we found that 73% (n = 94/128) of water sold in reusable containers in the Esmeraldas province of Ecuador was contaminated with coliform bacteria. In comparison, 25% (n = 9/36) of non-reusable bottles and 9% (n = 2/22) of water samples taken directly from the water treatment system contained coliform, suggesting that most observed bacterial contamination occurred due to inadequate cleaning of reusable bottles between use. The coliform contamination may pose a health risk to the Esmeraldas population. The present study may be indicative of similar situations in low- and middle-income countries around the world, given the widespread use of reusable bottles for water.

Although the effects of paternal alcoholism on the psychosocial adjustment of children are well documented, the impact of fathers' illicit drug abuse on their children is poorly understood. The purpose of this study was to compare the adjustment of children living in families with drug-abusing fathers (n = 40) with that of children with fathers who abused alcohol (n = 40) and children with non-substance-abusing fathers (n = 40). Children with drug-abusing fathers experienced more internalizing and externalizing symptoms than children with alcoholic or non-substance-abusing fathers. Interparental conflict and parenting behavior mediated the relationship between family type and children's adjustment. Interventions to improve fathers' parenting behavior and reduce partner conflict may lead to better adjustment among custodial children of drug-abusing fathers.

The purpose of this study was to examine the relationship between the psychosocial adjustment of children living in households of parents (N=112) in which fathers were entering treatment for substance abuse and the following sets of variables: (a) parents' sociodemographic characteristics, (b) parents' dyadic adjustment, (c) fathers' substance use severity, and (d) parents' psychological adjustment. Mothers did not meet current criteria for a psychoactive substance use disorder on alcohol or other drugs; moreover, based on reports by parents, none of the children was not exposed prenatally to illicit drugs. Results of hierarchical-by-blocks regression analyses revealed that each of the variable sets made a significant unique contribution to the prediction of children's psychosocial adjustment. Furthermore, the following variables within the sets were also found to be significant: (a) parents' age, (b) weekly family income, (c) frequency of male-to-female physical aggression between the parents, (d) frequency of fathers' substance use during the previous year, (e) diagnosis of antisocial personality disorder of fathers, and (f) mothers' level of psychological distress.

The purpose of the present investigation was to explore risk and preventive behaviors for potential HIV exposure among 362 married drug-abusing men entering outpatient treatment and their wives. During the year before entering treatment, 144 husbands (40%) reported they had engaged in sexual or drug use behaviors that placed them at high risk for HIV exposure. Nearly all of the wives of these husbands (n=138, 96%) reported they had sexual intercourse with their spouses during this same time period. Among these sexually active couples, 108 of the wives (78%) reported that condoms were not regularly used when they had intercourse with their spouses, thus placing them at high risk for indirect exposure to HIV. Seventy-seven (71%) of these 108 wives reported they were not aware their husbands had engaged in high risk behaviors and thus were unknowingly placed at high risk for indirect exposure to HIV. Among those couples with husbands who had engaged in a high risk behavior, longer marriages, a diagnosis of antisocial personality disorder for husbands, and wives' lack of knowledge of husbands' high risk behaviors were uniquely associated with an increased likelihood of wives being placed at high risk for indirect exposure to HIV.

The findings from earlier research suggest that courts adapt to prison overcrowding through the increased use of charge reductions and felony probation. Analyses with data aggregated from an urban county district court in Texas for each year from 1978 to 1988 did not support those earlier findings. During a period of unprecedented prison and court overloads, charge reductions and the probability of probation decreased, and sentences to state prisons increased. Average prison terms, however, decreased in length. The discussion in this article considers the implications of these findings for strict enforcement attempts and deterrence goals, in the context of what Pontell (1984) has called “a limited capacity to punish.”

The present study compared the psychosocial functioning of children whose fathers primarily abused illicit drugs other than alcohol (n = 51 ) to children from a demographically matched sample of families whose fathers abused alcohol (n = 51). Children with drug-abusing (DA) fathers exhibited significantly more negative child behaviors on a standardized child-rating scale than did children from homes with alcohol-abusing fathers. In addition, a significantly greater proportion of children with DA fathers met clinical cutoffs indicative of psychosocial impairment (n = 23: 45%) than did children whose fathers abused alcohol (n = 5; 10%). Mediation analyses indicated that severity of drug, legal, medical, employment, and family problems partially mediated the relationship between type of family (i.e., families with fathers who had an alcohol problem versus families with fathers who had a drug problem) and children's psychosocial adjustment.

The likelihood of male-to-female physical aggression on days of male partners' substance use, during a 15-month period, was examined. Participants were from married or cohabiting partner violent men entering a drug abuse treatment program (N=149). Compared to days of no drug or alcohol use, the likelihood of male-to-female physical aggression was significantly higher on days of substance use, after controlling for male partners' antisocial personality (ASP) disorder and couples' global relationship distress. Of the psychoactive substances examined, the use of alcohol and cocaine was associated with significant increases in the daily likelihood of male-to-female physical aggression; cannabis and opiates were not significantly associated with an increased likelihood of male partner violence.

Protein kinases are considered to be the second most important group of drug targets after G-protein-coupled receptors1, 2. Aberrant kinase activity is implicated in a variety of human diseases, in particular those involving inflammatory or proliferative responses, such as cancer, rheumatoid arthritis, cardiovascular and neurological disorders, asthma and psoriasis.

For the first time in over thirty years the Optical Society of America and the American Physical Society will meet together in Washington this month (21–25 April). The unusual nature of the meeting is reflected in a varied array of sessions and activities—among them, the celebration of the 75th Anniversary of the APS, special tutorial/review seminars in optics, the first Physics/Optics Show, a tour of the National Bureau of Standards facilities in Gaithersburg. Maryland, a Skylab Symposium featuring Owen Garriott of the Skylab II crew, and of course large numbers of invited and contributed papers.

Attempts to improve the reliability and validity of MMPI short forms appear warranted in light of their increasing acceptance among clinicians. Moreland (1983) has recently suggested that the most cost-effective way of improving existing MMPI short forms would be to include the entire K scale along with other abbreviated scales. The rationale for this suggestion includes the obvious improvement in the accuracy of the K scale as well as the expected improvement in those scales (Hs, Pd, Pt, Sc, and Ma) to which K corrections are added prior to scoring. Moreland (1983) compared the MMPI-168 with a version of the MMPI-168 containing the entire K scale (referred to as the MMPI-168E) by extracting both short forms from the MMPI protocols of 1181 psychiatric inpatients and 1258 normals. Utilization of the MMPI-168E increased the correlations between abbreviated and standard scales, especially for the Hs and Pd scales. This smdy is an attempt to determine whether the MMPI-168E is more effective than the MMPI-168 when the MMPI is used to make neurotic/psychotic discriminations using the Taulbee-Sisson (1957) signs. The full MMPls of 30 male and 28 female psychiatric inpatients were scored using the Taulbee-Sisson rules. This resulted in 13 neurotic, 19 psychotic, and 26 indeterminate classifications. The MMPI-168 and MMPI-168E were then extracted from the full MMPI and scored using the Taulbee-Sisson signs. Agreement with the full MMPI occurred in 7 (57%) of the neurotic, 6 (36%) of the Psychotic and 21 (84%) of the indeterminate classifications when the MMPI-168E was used. The corresponding numbers (percentages) for the MMPI-168 were 7 (61%) for the neurotic, 4 (26%) for the psychotic, and 21 (84%) for the indeterminate classifications. Inspection of the percentages indicates that inclusion of the full K scale in the MMPI-168 results in no increase in the accuracy with which the MMPI-168 predicts neurotic/psychotic diagnostic classifications of the full MMPI. Comparison of the two short forms with each other indicated agreement in classification in 53 of the 58 subjects. These data are consistent with the previous results in that they offer little or no reason to believe that one form is superior to the other. It should be noted that the two short forms were extracted from the full MMPI. It is not known if similar results would be found with independent administrations of the