Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[Q]: Context: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.', 'To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.', 'Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.', "Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.
Answer: The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.
[A]: Are the metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea influenced by ethanol?


[Q]: Context: To investigate the recent incidence of T1D in a US Midwestern county to determine whether this increase has been sustained and compare it with the incidence of celiac disease (CD) and also investigate the prevalence of CD, an associated autoimmune disease, within the cohort.', 'A broad search strategy was used to identify all incident cases of T1D in Olmsted County, Minnesota, between January 1, 1994, and December 31, 2010, using the Rochester Epidemiology Project. Diagnosis and residency status were confirmed through the medical record. Incidence rates were directly standardized to the 2010 US population. Poisson regression was used to test for a change in incidence rate. Clinical charts were reviewed to confirm case status.', 'There were 233 incident cases of T1D. Directly adjusting for age and sex with respect to the 2010 US white population, the overall annual incidence of T1D was 9.2 (95% CI, 8.0-10.4) per 100,000 people per year among all ages and 19.9 (95% CI, 16.6-23.2) per 100,000 people per year for those younger than 20 years. There was no significant increase in the incidence of T1D over time (P=.45). Despite the overall stability in annual incidence, there was an initial increasing trend followed by a plateau. Of the 109 patients with T1D (47%) tested for CD, 12% (13) had biopsy-proven CD.
Answer: The incidence of T1D has stopped increasing in Olmsted County, Minnesota, in the most recent decade. Further studies are needed to confirm this finding and explore reasons for this plateau.
[A]: Is incidence of Type 1 Diabetes Increasing in a Population-Based Cohort in Olmsted County , Minnesota , USA?


[Q]: Context: The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in the angiogenesis of both pathologic and nonpathologic conditions. However, the prognostic significance of VEGF and VEGFR expression in ovarian carcinoma is unclear.', 'The tissue expression levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 in 80 specimens of ovarian carcinoma were examined immnohistochemically. The results obtained were analyzed clinicopathologically.', 'VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 were expressed both in tumor cells and in adjacent endothelial cells of blood and lymph vessels. The tissue expressions of VEGF-C and VEGFR-2 were correlated significantly with tumor extension, including peritoneal metastases outside the pelvic cavity (P = 0.0010 and P = 0.0008, respectively), lymph node metastases (P = 0.0030 and P = 0.0018, respectively), and positive ascitic cytology (P = 0.025 and P = 0.0016, respectively). Conversely, there was no significant correlation between VEGF-A and VEGFR-3 expression and clinicopathologic features of ovarian carcinoma. Logistic regression analysis revealed that the expressions of VEGF-C and VEGFR-2 also were independent risk factors for peritoneal and lymph node metastases. Survival curves determined by the Kaplan-Meier method and in univariate analysis demonstrated that high expression levels of VEGF-C and VEGFR-2 were associated with the 5-year survival rate. In multivariate analysis, high expression levels of VEGF-C and VEGFR-2 emerged as independent indicators for disease-specific survival.
Answer: High tissue expression of VEGF-C and VEGFR-2 reflects the aggressiveness of the spread of tumor in ovarian carcinoma. Thus, both have predictive value for identifying high-risk patients who have a poor prognosis.
[A]:
Are vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 related closely to the prognosis of patients with ovarian carcinoma?