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: Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2(loxP/loxP) Villin-Cre mouse model for Lynch syndrome.', 'Flow cytometry was used for quantitation of mutation rates at a CA13 microsatellite in human colon cancer (HCT116) cells that had been stably transfected with pIREShyg2-enhanced green fluorescent protein/CA13, a reporter for frameshift mutations. Mice were treated for 43\u2005weeks with mesalazine, thymoquinone or control chow. Intestines were analysed for tumour incidence, tumour multiplicity and size. MSI testing was performed from microdissected normal intestinal or tumour tissue, compared with mouse tails and quantified by the number of mutations per marker (NMPM).', 'Besides mesalazine, thymoquinone significantly improved replication fidelity at 1.25 and 2.5\u2005µM in HCT116 cells. In Msh2(loxP/loxP) Villin-Cre mice, tumour incidence was reduced by mesalazine from 94% to 69% (p=0.04) and to 56% (p=0.003) by thymoquinone. The mean number of tumours was reduced from 3.1 to 1.4 by mesalazine (p=0.004) and to 1.1 by thymoquinone (p<0.001). Interestingly, MSI was reduced in normal intestinal tissue from 1.5 to 1.2 NMPM (p=0.006) and to 1.1 NMPM (p=0.01) by mesalazine and thymoquinone, respectively. Thymoquinone, but not mesalazine, reduced MSI in tumours.
Answer: Mesalazine and thymoquinone reduce tumour incidence and multiplicity in Msh2(loxP/loxP) Villin-Cre mice by reduction of MSI independent of a functional mismatch repair system. Both substances are candidate compounds for chemoprevention in Lynch syndrome mutation carriers.

Ex Output:
Do mesalazine and thymoquinone attenuate intestinal tumour development in Msh2 ( loxP/loxP ) Villin-Cre mice?


Ex Input:
Context: β1-Adrenergic receptor (β1-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The β1-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of β-blockers.', 'The effects of the β1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered β-blockers in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months by evaluating symptomatology, 12-lead ECGs, and Holter monitoring results.', 'Genetic differences in the antiarrhythmic efficacy of flecainide were observed in patients with coadministration of β-blockers. Tachyarrhythmia was well controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic efficacy was observed among the three genotypes in the patients without coadministration of β-blockers (64, 70, and 60%, respectively). Heart rate in tachyarrhythmia in patients treated with flecainide was significantly higher in Gly389 carriers than in Arg389-homozygotes (P=0.013).
Answer: The Gly389 polymorphism decreased the antiarrhythmic efficacy of flecainide when coadministered with β-blockers. The results indicate that the Arg389Gly polymorphism may play an important role in predicting the efficacy of flecainide in patients with coadministration of β-blockers.

Ex Output:
Does β1-Adrenergic receptor Arg389Gly polymorphism affect the antiarrhythmic efficacy of flecainide in patients with coadministration of β-blockers?


Ex Input:
Context: To determine whether intratrigonal Onabotulinum toxin A (OnabotA) injection produces a different symptomatic outcome and duration of effect on ulcerative (Ulc) and nonulcerative (NUlc) bladder pain syndrome/interstitial cystitis (BPS/IC) patients and to compare the urinary levels of neurotrophines (NGF, BDNF, and GDNF) in response to OnabotA.', "Ten Ulc and 14 NUlc bladder pain syndrome/interstitial cystitis patients were included in this study. OnabotA (100 U) was injected in 10 trigonal sites, each receiving 10 U in 1 mL of saline. Outcome measures included pain visual analog scale (0-10), a 3-day voiding chart, O'Leary-Sant Score (OSS), and quality of life (QoL) from International Prostate Symptoms Score assessed before treatment, 1 month after injection, and every 3 months afterwards. Urinary NGF, BDNF, and GDNF were accessed using ELISA, at same time points. Treatment duration was determined at the time patients requested another injection.", 'Patients had a mean age of 40 ± 12 years in the Ulc and 47 ± 13 years in the NUlc group (ns). Mean values at baseline of pain intensity, frequency, nocturia, OSS, QoL, and urinary NGF, BDNF, GDNF were identical in the 2 groups. Patients with the Ulc phenotype had a longer duration of symptoms (28.8 ± 11 vs 19.2 ± 8 months, P = .018). Both groups responded equally to OnabotA, with significant improvements in pain intensity, frequency, nocturia, OSS, QoL, and urinary NGF, BDNF, GDNF. The effect lasted for 9 ± 2.8 (Ulc) and 10.5 ± 2 (NUlc) months.
Answer: In this cohort, Ulc and NUlc patients had similar symptoms at baseline and comparable clinical response to intratrigonal OnabotA. These findings suggest that pain may not be directly related with ulcers themselves.

Ex Output:

Do ulcerative and nonulcerative forms of bladder pain syndrome/interstitial cystitis differ in symptom intensity or response to onabotulinum toxin A?