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Screening Campaigns (screening + campaign)
Selected AbstractsIdentification of small molecule aggregators from large compound libraries by support vector machinesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 4 2010Hanbing Rao Abstract Small molecule aggregators non-specifically inhibit multiple unrelated proteins, rendering them therapeutically useless. They frequently appear as false hits and thus need to be eliminated in high-throughput screening campaigns. Computational methods have been explored for identifying aggregators, which have not been tested in screening large compound libraries. We used 1319 aggregators and 128,325 non-aggregators to develop a support vector machines (SVM) aggregator identification model, which was tested by four methods. The first is five fold cross-validation, which showed comparable aggregator and significantly improved non-aggregator identification rates against earlier studies. The second is the independent test of 17 aggregators discovered independently from the training aggregators, 71% of which were correctly identified. The third is retrospective screening of 13M PUBCHEM and 168K MDDR compounds, which predicted 97.9% and 98.7% of the PUBCHEM and MDDR compounds as non-aggregators. The fourth is retrospective screening of 5527 MDDR compounds similar to the known aggregators, 1.14% of which were predicted as aggregators. SVM showed slightly better overall performance against two other machine learning methods based on five fold cross-validation studies of the same settings. Molecular features of aggregation, extracted by a feature selection method, are consistent with published profiles. SVM showed substantial capability in identifying aggregators from large libraries at low false-hit rates. © 2009 Wiley Periodicals, Inc.J Comput Chem, 2010 [source] High-risk HPV types in Tunisia.JOURNAL OF MEDICAL VIROLOGY, Issue 7 2006A pilot study reveals an unexpectedly high prevalence of types 5, lack of HPV 18 among female prostitutes Abstract "High-risk" HPVs (HR-HPV) have sharply different prevalences and there is evidence to suggest this may vary according to regions. Accurate description of HR-HPV circulation is a key feature for the rational design of prevention and screening campaigns. To gain insight into HR-HPV circulation in Tunisia, a pilot study was carried out on 64 healthy prostitutes working in the Tunis area. HPV detection and typing were carried out by MY09/MY11 PCR and restriction fragment length polymorphism (RFLP). A selected set of samples was also assayed by Gp5+/Gp6+ PCR and typed by direct sequencing. Out of 64 women, 28 were HPV positive. HPV-16 and HPV-58, both members of the genus Alpha-Papillomavirus, species 9, accounted for 10 and 7 cases with a prevalence rate of 38% and 27%, respectively. HPV-82, a member of species 5, ranked third with four cases (,15%). Types 31, 33, 35; all members of species 9 were each detected once (,4%) while neither HPV-18 nor related members of species 7 were detected. Type 72 and 83, both members of species 3, were the only low-risk types, each detected only once (4% each). Two samples could not be typed. The prevalence of HPV types appeared sharply different from that of neighboring areas. Should the existence of epidemiological pockets be confirmed by larger, more detailed studies, screening and vaccine campaigns will have to be designed carefully taking into account the actual epidemiological context of the target population. J. Med. Virol. 78:950,953, 2006. © 2006 Wiley-Liss, Inc. [source] Comparative enzymology of native and recombinant house dust mite allergen Der p 1ALLERGY, Issue 3 2009J. Zhang Background:, The cysteine peptidase activity of group 1 house dust mite allergens is important for their allergenicity and may offer new therapeutic targets for allergy treatment. Hitherto, the design of specific inhibitors has been impeded because the availability of pure, fully active allergens has limited the implementation of drug screening campaigns. Similarly, investigation of the mechanisms by which peptidase allergens promote sensitization has also been restricted. Our aim was to compare the enzymology of recombinant and native forms of Der p 1 to establish if an easily expressed recombinant form of Der p 1 could be used as a drug discovery tool. Methods:, Enzymatic activity of natural and recombinant Der p 1 was compared fluorimetrically using a novel specific substrate (ADZ 50,059) and a novel specific active site titrant (ADZ 50,000). The effect of recombinant Der p 1 prodomain on the catalytic activity of both Der p 1 preparations was also examined. Results:, Although differing substantially in molecular weight, the enzymological properties of recombinant and native Der p 1 were indistinguishable. Our data show clearly by experiment that, in contrast to some suggestions, Der p 1 is not an enzyme of bifunctional mechanism. Conclusion:, The catalytic activity of Der p 1 is tolerant of glycosylation differences that occur at N150 when the protein is expressed in Pichia pastoris. This suggests that this recombinant protein may be suitable for drug design studies and in the elucidation of how peptidase activity promotes sensitization to peptidase and nonpeptidase bystander allergens. [source] Beliefs about bowel cancer among the target group for the National Bowel Cancer Screening Program in AustraliaAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2010Geoffrey Jalleh Abstract Objective: To assess awareness of and intentions and self-reported participation in the National Bowel Cancer Screening Program (NBCSP) in Australia and the program's impact on knowledge of and beliefs about bowel cancer. Method: Cross-sectional, computer-assisted telephone surveys of Western Australians aged 55,74 years conducted in April 2007 (n = 505) and June 2008 (n = 500) measured beliefs about the prevalence of bowel cancer, its preventability, impact of early detection on life expectancy, knowledge of the symptoms and tests for bowel cancer, and awareness of and participation in the NBCSP. Results: In 2008, awareness of the Program was 58%. Seventy-seven per cent of those invited to participate in the program agreed to do so. The vast majority believed bowel cancer to be preventable (83%), with early treatment making ,a great deal of difference' to life expectancy (85%). Awareness of blood in faeces as a sign of bowel cancer increased from 64% in 2007 to 75% in 2008 (p<0.01). Awareness of FOBT as a test for bowel cancer increased from 54% in 2007 to 70% in 2008 (p<0.01). Conclusions: The NBCSP appears to have increased knowledge of bowel cancer. Implications: Education and screening campaigns are required to further increase perceived prevalence of bowel cancer and to increase knowledge of symptoms and risk factors. [source] Trends in PSA, age and prostate cancer detection among black and white men from 1990-2006 at a tertiary care centerCANCER, Issue 16 2010Jeannette M. Potts MD Abstract BACKGROUND: Prostate cancer is the most frequently diagnosed malignancy in men in the United States, with even higher prevalence and death rates among black men. The authors sought to compare trends in prostate-specific antigen (PSA), age, and prostate-cancer detection among black and white men in our region during a 16-year period. METHODS: This was a retrospective study of patient archives between 1990 through 2006. Data collection was accomplished by examining patients' charts and electronic medical records. Data from 5570 patients, of whom 911 were black, were analyzed statistically by testing and comparing parameters over time. RESULTS: During this 16-year period, mean age at the time of initial diagnostic prostate biopsy did not change in either group, despite what we had believed about the effects of patient education and screening campaigns. However, prostate-cancer detection rates did decrease during the time period studied. Over time, the authors also observed significant decreases in the sensitivity and specificity of PSA as a screening tool. Indeed, analysis of more recent cases demonstrated a positive predictive value comparable to a coin toss. While Gleason scores remained relatively stable over time, reporting of prostate intraepithelial neoplasia (PIN) and inflammation increased. CONCLUSIONS: Using lower PSA thresholds, promoting younger screening age, and increasing efforts to educate the public have not seemed to influence age at time of diagnostic testing, which may reflect other factors such as usefulness of screening, physician referral patterns, patient compliance, and other sociodemographic issues. The usefulness of PSA as a screening tool appears to be diminishing. Cancer 2010. © 2010 American Cancer Society. [source] | ||||||||||