In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Q: Context: Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community.', 'We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses.', 'This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory.\Question: Does meta-analysis of the p53 mutation database for mutant p53 biological activity reveal a methodologic bias in mutation detection?

A: We show the importance of accurate functional analysis before inferring any genetic variation. The quality of the p53 databases is essential in order to prevent erroneous analysis and/or conclusions. The availability of functional data from our new p53 web site (http://p53.free.fr and http://www.umd.be:2072/) will allow functional prescreening to identify potential artifactual data.
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Q: Context: Our previous work demonstrated altered messenger RNA expression of integrin -5 and -8, using an in silico analysis of publically available data from patients with biliary atresia (BA); however, we were unable to demonstrate statistically significant differences in protein expression because of sample size. In the present study, we repeated the analysis of liver fibrosis and protein expression of the integrins in a larger cohort of patients with BA and compared them with patients undergoing liver biopsy for other diagnoses, with the hypothesis that 1 of the integrins would be differentially expressed.', 'Liver specimens were obtained at 2 collaborating institutions. Samples from infants with BA (n = 23) were compared with samples from those who underwent liver biopsy for neonatal hepatitis (n = 9). All of the specimens were analyzed by 2 pathologists (C.R. and R.A.), who were blinded to the diagnoses. Standard Ishak scoring was performed to evaluate fibrosis and inflammation, and immunohistochemical (IHC) positivity was graded from 0 to 4. Comparisons between the IHC positivity and Ishak scoring for the BA and control groups were performed using the Student t test with P < 0.01 considered significant because of the multiple comparisons. Interobserver variability was assessed by intraclass correlation (ICC).', 'Pooled analysis from specimens from patients with BA showed significantly more fibrosis than controls based on Ishak scores (3.21 1.82 vs 1.17 1.00, P < 0.005). IHC evaluation showed increased integrin 8 protein expression when compared with controls (2.67 0.81 vs 1.72 0.62, P < 0.005); however, there were no significant differences in integrin 5 (1.93 0.84 vs 1.50 0.90, P = 0.23) or integrin 6 (0.85 1.20 vs 0.94 0.85, P = 0.82) expression. These data were confirmed on individual analysis. Interobserver agreement was fair for integrin 5 (ICC 0.52), good for integrin 6 (ICC 0.72), and excellent for integrin 8 (ICC 0.79) and fibrosis (ICC 0.89).\Question: Is integrin -8 , but not -5 or -6 , protein expression increased in livers of children with biliary atresia?

A: Our data show that integrin 8, but not integrin 5 or integrin 6, protein expression is increased in liver specimens of patients with BA. These data support the mounting evidence that transforming growth factor- (TGF-) activation is responsible for the fibrosis found in BA. Anti-integrin 8 or more global integrin blocking strategies may be therapeutic options in BA, but further work is clearly needed.
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Q: Context: There have been conflicting results from studies to determine whether factors unrelated to endoscopist skill, such as fatigue, affect the quality of screening colonoscopy. We studied the effects of human and system factors on screening colonoscopy withdrawal time and likelihood of detecting an adenoma in a large cohort of patients.', 'We performed a retrospective analysis of operation and quality improvement data in colonoscopies performed at single academic medical center from November 2012 through February 2014. We collected data from the Northwestern Medicine Enterprise Data Warehouse on endoscopy procedure reports, patient demographics, and pathology reports of all patients undergoing endoscopy. We identified all screening colonoscopies during the study period and determined whether an adenoma was identified in each screening colonoscopy procedure. Our study included data from 7004 screening colonoscopies of patients 50-75 years old performed by endoscopists who performed at least 100 screening colonoscopies during the study period (n = 18).', 'Approximately 27% of procedures began on time; the median colonoscope insertion time was 5.9 minutes (interquartile range, 4.0-8.6). In multivariable logistic regression analysis adjusting for covariates and endoscopist-level clustering, adenoma detection was not associated with procedure delay (P = .48), hour of day (P = .40), or performing the second of 2 colonoscopy blocks in 1 day (P = .88). Adenoma detection was associated with insertion time overall (P = .006), but there was no consistent directional relationship across insertion quintiles.\Question: Are procedure Delays and Time of Day Associated With Reductions in Quality of Screening Colonoscopies?

A:
Procedure delays and measured factors associated with fatigue, including time of day and multiple procedure blocks, do not reduce the odds of detecting an adenoma. Adenoma detection varies widely among providers, so efforts to improve adenoma detection should focus mainly on optimizing physician skill.
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