TASK DEFINITION: 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.
PROBLEM: 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).

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

PROBLEM: To investigate the association between adenoidectomy and/or tonsillectomy in childhood and asthma, allergic rhinitis (AR), and eczema in adolescence.', 'Longitudinal birth cohort study of 1328 members born in the city of Nijmegen. Information on ear-nose-throat surgery was documented at 2, 4, and 8 years of age. In 1055 cohort members the incidence of asthma, AR, and eczema at 21 years of age was determined using the International Study of Asthma and Allergic disease in Childhood Core Questionnaire. To analyse the association between adenoidectomy and/or tonsillectomy in childhood and asthma, AR, and eczema at age 21 years, relative risks (RR) were calculated.', 'Six hundred and ninety-three (66%) members completed the questionnaire at age 21 years, of whom 104 (15%) had undergone adenoidectomy and/or tonsillectomy and 262 (38%) reported atopic disease. Children who underwent adenoidectomy and/or tonsillectomy before the age of 8 years were not more likely to develop asthma, AR, or eczema at the age of 21 years than children who did not; RR 0.93 (95% confidence limits (CL) 0.52-1.64), RR 0.94 (CL 0.68-1.30), and RR 1.00 (CL 0.59-1.68), respectively.

SOLUTION: Is adenoidectomy and/or tonsillectomy in childhood associated with atopic disease later in life?

PROBLEM: Immune dysregulation can affect insulin resistance (IR) and β-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM.', 'Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study.', 'Over the 7-year period, C3 levels (per 0.1 g/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; β = 15.2% [95% CI 12.9-17.6]), hepatic IR (β = 6.1% [95% CI 4.7-7.4]), adipocyte IR (β = 16.0% [95% CI 13.0-19.1]), fasting glucose (β = 1.8% [95% CI 1.2-2.4]), 2-h glucose (β = 5.2% [95% CI 3.7-6.7]), and area under the curve for glucose (β = 3.6% [95% CI 2.7-4.6]). In addition, greater changes in C3 (per 0.1 g/L) were associated with greater changes in HOMA2-IR (β = 0.08 [95% CI 0.02-0.15]) and greater changes in hepatic IR (β = 0.87 [95% CI 0.12-1.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1-2.0]).

SOLUTION:
Is complement factor 3 associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period : the CODAM Study?