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: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-β1), and interferon gamma (IFN-γ) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.

Output: Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?


Input: Consider Input: Beta blockers and calcium antagonists are widely used in the management of angina pectoris in the belief that the combination is more efficacious than either drug alone.', 'This double blind randomised crossover placebo controlled study compares the effects of nicardipine, atenolol and their combination in 30 patients with chronic stable angina. Each treatment period lasted 6 weeks with dose titration after 3 weeks. Symptom limited treadmill exercise testing and radionuclide ventriculography at rest was carried out at the end of each treatment period.', 'Total exercise duration and time to 1-mm ST-segment depression was significantly prolonged by nicardipine and atenolol when compared to placebo, the combination offered no additional benefit. Time to onset of angina was significantly prolonged by nicardipine and the combination but not by atenolol. Indices of left ventricular function were not significantly affected by any treatment other than an increase in left ventricular end diastolic volume on atenolol and the combination.

Output: Is atenolol or nicardipine alone as efficacious in stable angina as their combination : a double blind randomised trial?


Input: Consider Input: In primary care surveillance systems based on voluntary participation, biased results may arise from the lack of representativeness of the monitored population and uncertainty regarding the population denominator, especially in health systems where patient registration is not required.', 'Based on the observation of a positive association between number of cases reported and number of consultations by the participating general practitioners (GPs), we define several weighted incidence estimators using external information on consultation volume in GPs. These estimators are applied to data reported in a French primary care surveillance system based on voluntary GPs (the Sentinelles network) for comparison.', 'Depending on hypotheses for weight computations, relative changes in weekly national-level incidence estimates up to 3% for influenza, 6% for diarrhea, and 11% for varicella were observed. The use of consultation-weighted estimates led to bias reduction in the estimates. At the regional level (NUTS2 level - Nomenclature of Statistical Territorial Units Level 2), relative changes were even larger between incidence estimates, with changes between -40% and +55%. Using bias-reduced weights decreased variation in incidence between regions and increased spatial autocorrelation.


Output: Does improving disease incidence estimate in primary care surveillance systems?