Given a passage, 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:
MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival.', 'Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.', 'The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.461.45 versus 1.920.65, P< 0.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P=0.003) and tumor stage (P=0.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value=5.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P=0.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P<0.001; hazard ratio 6.17; 95% CI 2.33 to 10.39).

Ex Output:
Is increased expression of miR-222 associated with poor prognosis in bladder cancer?

Ex Input:
SPARC (secreted protein acidic, rich in cysteine) is a matricellular protein that has been found to be activated in a number of human cancers. More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo.', 'SPARC upregulation was determined in intestinal adenomas of tumour-prone Apc(Min/+) mice at both the RNA and the protein level. To determine the functional importance of SPARC for intestinal tumorigenesis we then intercrossed Sparc knockout mice with Apc(Min/+) mice (n = 20). Intestinal enterocyte migration was examined using bromodeoxyuridine labelling studies.', 'Levels of murine Sparc and several related proteins were upregulated in adenomas arising in Apc(Min/+) mice. A deficiency of Sparc strongly suppressed adenoma formation in Apc(Min/+) mice (p>or=0.0001). Importantly, a deficiency of Sparc also accelerated enterocyte migration (p = 0.01), as perturbed slow epithelial migration may underpin adenoma formation in the intestine.

Ex Output:
Does deficiency of SPARC suppress intestinal tumorigenesis in APCMin/+ mice?

Ex Input:
Circadian control of behavior and physiology is a central characteristic of all living organisms. The master clock in mammals resides in the hypothalamus, where the suprachiasmatic nucleus (SCN) synchronizes daily rhythms. A variety of recent evidence indicates that the neuropeptide vasoactive intestinal peptide (VIP) is critical for normal functioning of the SCN. The aim of our study was to examine the possible role of VIP in driving circadian rhythms in the hypothalamic-pituitary-adrenal axis.', 'Circulating ACTH and corticosterone concentrations were determined by round-the-clock sampling under diurnal and circadian conditions. The responsive aspects of the hypothalamic-pituitary-adrenal axis were tested by application of acute stress by footshock and light.', 'We demonstrate that the circadian rhythms in ACTH and corticosterone are lost in VIP-deficient mice. The ability of light to induce a corticosterone response was also compromised in the mutant mice, as was photic induction of Per1 in the adrenal glands. In contrast, the acute stress response was apparently unaltered by the loss of VIP.

Ex Output:
Is vasoactive intestinal peptide critical for circadian regulation of glucocorticoids?