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: Cardiac overexpression of the β-adrenoreceptor (βAR)-coupled stimulatory G-protein subunit Gαs enhances inotropic responses to adrenergic stimulation and improves survival in mice under βAR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding Gαs, with the greatest Gαs protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving βAR blockade.', 'This prospective analysis included 1,627 European ancestry patients undergoing primary coronary artery bypass graft surgery. Patients were genotyped for two GNAS haplotype tagging single-nucleotide polymorphisms defining three major haplotypes. Up to 5-yr all-cause mortality was estimated using a Cox proportional hazard model; hazard ratios and 95% CIs were calculated while adjusting for demographics, clinical covariates, and the new EuroSCORE II.', 'Univariate analysis revealed haplotype-dependent 5-yr mortality rates (*1/*1: 18.9%, *2/*1: 13.7%, *2/*2: 9.3%, *3/*1: 10.6%, *3/*2: 9.1%, and *3/*3: 9.6%; P = 0.0006). After adjustment for other predictors of death, homozygote haplotype *1 carriers showed a doubled risk for death (hazard ratio, 2.2; 95% CI, 1.2 to 3.8; P = 0.006). Considering only patients receiving βAR blockers (n = 1,267), the adjusted risk of death even tripled (hazard ratio, 3.0; 95% CI, 1.5 to 6.1; P = 0.002).
Answer: GNAS haplotypes independently associate with an increased risk of death after primary coronary artery bypass graft surgery. These results are most pronounced in patients receiving βAR blockers, strengthening the rationale for personalized treatment, to decrease medication side effects and improve outcomes.

Ex Output:
Do gNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting?


Ex Input:
Context: To assess prospectively the impact of psychiatric disorders on risk for exacerbations. The course of chronic obstructive pulmonary disease (COPD) is punctuated by acute exacerbations. Although anxiety and mood disorders are common in patients with COPD, no studies have assessed prospectively the association between these disorders and exacerbations.', "Psychiatric disorders were evaluated by a structured psychiatric interview in 110 patients (51% women, age (mean +/- standard deviation) = 66 +/- 8 years) with stable COPD and previous admission for exacerbations recruited from two outpatient clinics. Patients were followed for a mean of 2 years and both inpatient-treated (i.e., treated in the emergency department or hospital) and outpatient-treated (i.e., treated with medication in the patient's own environment) exacerbations were recorded.", 'Independent of covariates, patients with psychiatric disorders exhibited a significantly higher weighted annual rate of exacerbations treated in an outpatient setting after adjustment for covariates (3 versus 2, p = .003) than patients without psychiatric disorders, but no difference in exacerbations treated in the inpatient setting. They were also at a higher risk for any (relative risk (RR) = 1.56, 95% Confidence Interval (CI) = 1.02-2.37) and outpatient (RR = 1.68, 95% CI = 1.08-2.59) exacerbations, but not inpatient exacerbations (RR = 1.36, 95% CI = 0.82-2.25).
Answer: Patients with psychiatric disorders are at greater risk of exacerbations treated in an outpatient setting but not those treated in an inpatient setting. These outpatient-managed exacerbations account for a significant proportion of the healthcare burden for COPD, so interventions should target patients with psychiatric disorders to improve management of COPD.

Ex Output:

Are chronic obstructive pulmonary disease patients with psychiatric disorders at greater risk of exacerbations?