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.

Input: Consider Input: ID4 gene is a member of the inhibitor of DNA binding (ID) family proteins that inhibit DNA binding of basic helix-loop-helix transcription factors. The epigenetic inactivation of ID4 gene on colorectal cancer (CRC) development and its clinical significance was assessed.', 'In CRC cell lines, ID4 methylation status of the promoter region was assessed by methylation-specific PCR and bisulfite sequencing. The mRNA expression level was assessed by quantitative real-time reverse transcription-PCR. The methylation status of 9 normal epithelia, 13 adenomas, 92 primary CRCs, and 26 liver metastases was assessed by methylation-specific PCR. ID4 protein expression was assessed by immunohistochemistry analysis of tissue specimen.', 'CRC cell lines were shown to be hypermethylated, and mRNA expression was suppressed and could be restored by 5-aza-cytidine treatment. In clinical specimens from normal epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4 hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26 (73%), respectively, with a significant elevation according to CRC pathological progression. Methylation status of primary CRCs significantly correlated with histopathological tumor grade (P = 0.028). Immunohistochemistry analysis showed ID4 expression of normal colon epithelia, adenomas, and unmethylated primary CRCs but not hypermethylated CRC specimens. Among 76 American Joint Committee on Cancer stage I to IV patients who had undergone curative surgical resection, overall survival was significantly poorer in patients with hypermethylated ID4 bearing tumors (P = 0.0066).

Output: Does epigenetic inactivation of ID4 in colorectal carcinomas correlate with poor differentiation and unfavorable prognosis?


Input: Consider Input: Obese persons have low circulating natriuretic peptide (NP) concentrations. It has been proposed that this 'natriuretic handicap' could play a role in obesity-related hypertension. The normal physiological response of the NP system to an increase in blood pressure (BP) is an increase in NP secretion with concomitant higher circulating NP concentrations. In this study, we investigated whether higher BP would also be related to higher circulating NP concentrations in obese men; furthermore, we verified that BP had affected the hearts of our study participants, by determining left ventricular mass (LVM).", 'We examined 103 obese healthy medication-free men. We measured 24-hour ambulatory BP (ABP). LVM was calculated using the Cornell voltage-duration product method. Fasting serum concentrations of midregional proatrial NP (MR-proANP), a surrogate for active ANP, were measured. Linear regression analysis was used to calculate age-adjusted standardised regression coefficients (β).', 'LVM and BP increased across systolic ABP quartiles (mean LVM±SD: 1599.1±387.2\u2005mm\u2005ms in first vs 2188.5±551.3\u2005mm\u2005ms in fourth quartile, p<0.001; mean systolic ABP±SD: 114.5±4.2\u2005mm\u2005Hg in first vs 149.0±7.7\u2005mm\u2005Hg in fourth quartile, p<0.001). Systolic ABP was robustly associated with LVM (ß=0.48, p<0.001). Despite evidence of BP-related increases in LVM, serum MR-proANP was negatively associated with systolic ABP (ß=-0.32, p=0.004) and with diastolic ABP (ß=-0.45, p<0.001).

Output: Does serum proatrial natriuretic peptide increase with higher systolic blood pressure in obese men?


Input: Consider Input: Tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical results in medullary thyroid carcinoma (MTC) patients. However, the considerable variability in patient response to treatment with TKIs remains largely unexplained. There is evidence that it could be due, at least in part, to alterations in genes associated with the disease via their effect on the expression of TKI targets. The objective of this study was to evaluate the influence of RAS mutations on the expression levels in MTC tumors of eight key TKI target proteins.', 'We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, and VEGFR3 in a series of 84 primary MTC tumors that had previously been molecularly characterized, including 14 RAS-positive, 18 RET(M918T)-positive, and 24 RET(C634)-positive tumors, as well as 15 wild-type tumors with no mutations in the RET or RAS genes.', 'In contrast to RET-positive tumors, RAS-positive tumors expressed neither PDGFRB nor MET (p=0.0060 and 0.047, respectively). Similarly, fewer RAS-positive than RET-related tumors expressed VEGFR3 (p=0.00062). Finally, wild-type tumors expressed VEGF more often than both RAS- and RET-positive tumors (p=0.0082 and 0.011, respectively).


Output: Is vEGF , VEGFR3 , and PDGFRB protein expression influenced by RAS mutations in medullary thyroid carcinoma?