TASK DEFINITION: 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.
PROBLEM: 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?

SOLUTION: 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.

PROBLEM: Context: Hepatic osteodystrophy has been reported in patients with various chronic liver diseases, including liver cirrhosis. However, it has not been well investigated in patients with hepatitis B virus infection. The aim of this study was to investigate the association between hepatitis B surface antigen (HBsAg) seropositivity and bone mineral density (BMD) in a population representative of normal Koreans.', 'Subjects with both HBsAg and BMD levels examined during the 2008-2010 Korea National Health and Nutrition Examination Surveys were included. HBsAg-seropositive (+) subjects were compared with those who were HBsAg-seronegative (-). BMD was measured at the lumbar spine and femur by dual-energy X-ray absorptiometry. Multivariable logistic regression was performed for BMD .', 'In total, 11,306 participants were included in this study, among which 423 (3.7\xa0%) were HBsAg(+): 153 premenopausal female (3.4\xa0%), 83 postmenopausal female (3.5\xa0%), and 187 male (4.2\xa0%). Multivariable logistic regression analysis adjusted for age and body mass index showed that HBsAg(+) male had significantly lower BMD of the femoral neck than HBsAg(-) male (0.810\xa0±\xa00.009 vs. 0.827\xa0±\xa00.002\xa0g/cm(2), p\xa0=\xa00.035). Further adjustment for waist circumference, smoking, drinking, exercise, income, occupation, and vitamin D levels showed that HBsAg(+) male had significantly lower BMD of the femur neck (0.810\xa0±\xa00.010 vs. 0.831\xa0±\xa00.002\xa0g/cm(2), p\xa0=\xa00.032) and lumbar spine (0.953\xa0±\xa00.011 vs. 0.974\xa0±\xa00.003\xa0g/cm(2), p\xa0=\xa00.049) than HBsAg(-) male.\Question: Are males seropositive for hepatitis B surface antigen at risk of lower bone mineral density : the 2008-2010 Korea National Health and Nutrition Examination Surveys?

SOLUTION: HBsAg seropositivity was significantly associated with lower BMD in male. Future long-term prospective studies investigating bone turnover markers and hormones are needed to better understand the pathophysiology and clinical significance of chronic hepatitis B virus-related hepatic osteodystrophy.

PROBLEM: Context: The goal was to test the hypothesis that extremes of PaCO2 during the first 4 days after birth are associated with severe intraventricular hemorrhage (grades 3 and 4).', 'A single-center retrospective review of clinical and blood gas data in the first 4 postnatal days for 849 infants with birth weights of 401 to 1250 g was performed. The univariate and multivariate relationships of severe intraventricular hemorrhage with maximal and minimal PaCO2, PaCO2 averaged over time (time-weighted PaCO2), and measures of PaCO2 fluctuation (SD of PaCO2 and difference in PaCO2 [maximum minus minimum]) were assessed.', 'Birth weight (mean +/- SD) was 848 +/- 212 g, and the median gestational age was 26 weeks. Infants with severe intraventricular hemorrhage had higher maximal PaCO2 (median: 72 vs 59 mm Hg) and time-weighted PaCO2 (mean: 49 vs 47 mm Hg) values but lower minimal PaCO2 values (32 vs 37 mm Hg). High PaCO2, low PaCO2, SD of PaCO2, and difference in PaCO2 predicted severe intraventricular hemorrhage, but time-weighted average PaCO2 was not as predictive.\Question: Are both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure associated with severe intraventricular hemorrhage in preterm infants?

SOLUTION:
Both extremes and fluctuations of PaCO2 are associated with severe intraventricular hemorrhage. It may be prudent to avoid extreme hypocapnia and hypercapnia during the period of risk for intraventricular hemorrhage.