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.

Ex Input:
Context: Side effects of mitotane (o,p'-DDD) have suggested estrogenic effects.", "The objective of the study was to explore o,p'-DDD potential estrogenic effect on SHBG and corticosteroid-binding globulin (CBG).", 'Human hepatoma cell lines (HepG2), lacking estrogen receptor (ER)-alpha, and Hep89, stably transfected by ERalpha, were used.', 'The study was conducted at an academic research laboratory and medical center.', 'The study included 10 male patients with recurrent adrenal carcinoma, receiving mitotane (4-6.5 g daily) for more than 6 months.', 'The main outcome measures were SHBG/CBG mRNA levels measured by real-time PCR, culture medium SHBG/CBG concentrations measured by specific immunoassays, and transient transfection experiments with human SHBG proximal promoter reporter constructs.', "Increased serum SHBG and CBG concentrations, which exceeded normal male limits, were observed in most mitotane-treated patients. In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations. In contrast, in the Hep89 cell line, E2 increased concentrations of SHBG (r = 0.44, P < 0.0001) and CBG (r = 0.585, P < 0.0001) secreted into culture media in a dose-dependent manner. o,p'-DDD significantly increased SHBG (150% vs. control, P < 0.05) and CBG (184% vs. control, P < 0.05) production by Hep89 cells, at a concentration of 2 x 10(-5) m. Transient transfection experiments in Hep89 cells showed that E2 or o,p'-DDD treatment did not increase the transcriptional activity of the minimal proximal promoter of human SHBG gene.
Answer: Mitotane increased SHBG/CBG gene expression and liver production by mechanisms requiring the presence of ERalpha.

Ex Output:
Does mitotane have an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans?


Ex Input:
Context: Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS).', 'Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size.', 'In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories.
Answer: Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions.

Ex Output:
Does tumor size improve the accuracy of TNM predictions in patients with renal cancer?


Ex Input:
Context: This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes.', 'This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720\xa0cm/s), carotid atherosclerosis (intima-media thickness\xa0>0.8\xa0mm or the presence of plaques), and carotid stenosis (≥50\xa0% of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed.', 'Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles.
Answer: Serum GGT levels were significantly associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but not with the early and late stages of atherosclerotic vascular changes, in patients with type 2 diabetes. Serum GGT level may not be a reliable marker of subclinical atherosclerosis in type 2 diabetes.

Ex Output:

Is serum gamma-glutamyltransferase associated with subclinical atherosclerosis in patients with type 2 diabetes?