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: Formation of branching tubes is a fundamental step in the development of glandular organs. To identify extracellular cues that orchestrate epithelial tubulogenesis, we employed an in vitro assay in which EpH4-J3B1A mammary epithelial cells form spheroidal cysts when grown in collagen gels under serum-free conditions, but form branching tubules in the presence of fetal calf serum (FCS).', 'Initial experiments showed that the tubulogenesis-inducing activity of FCS was markedly increased by heating (70 degrees C) or transient acidification to pH3. We therefore hypothesized that the tubulogenic agent was transforming growth factor-beta (TGF-beta), a cytokine that is present in serum in latent form and can be activated by heat or acid treatment. We found indeed that the tubulogenic activity of acidified FCS is abrogated by addition of either SB-431542, a selective inhibitor of the TGF-beta type I receptor, or a neutralizing antibody to TGF-beta-1. On the other hand, addition of low concentrations (20-100 pg/ml) of exogenous TGF-beta-1 recapitulated the effect of acidified FCS in inducing morphogenesis of hollow tubes. In contrast, higher concentrations of TGF-beta-1 induced the formation of thin cellular cords devoid of a detectable lumen. To gain insight into the mechanisms underlying TGF-beta-1-induced tube formation, we assessed the potential role of matrix metalloproteinases (MMPs). By western blot and gelatin zymography, we observed a dose-dependent increase in MMP-9 upon TGF-beta-1 treatment. Tube formation was suppressed by a synthetic broad-spectrum metalloproteinase inhibitor, by recombinant tissue inhibitor of metalloproteinases-2 (TIMP-2) and by a selective inhibitor of MMP-9, indicating that this morphogenetic process requires the activity of MMP-9.

Output: Do low concentrations of transforming growth factor-beta-1 induce tubulogenesis in cultured mammary epithelial cells?


Input: Consider Input: A higher anticholinergic risk score (ARS) is associated with an increased risk of anticholinergic adverse effects in elderly patients. It is unknown whether factors other than the use of anticholinergic drugs determine the ARS.', 'A comprehensive medical record review was conducted in 155 consecutive hospitalised patients (median age 79.0 years, interquartile range 66.0-86.0). Information was collected on: demographics; clinical characteristics (including medications and their doses); history of anticholinergic-induced adverse effects; and biochemical markers of hepatic and renal function (serum albumin concentrations and estimated glomerular filtration rate, eGFR). The ARS was calculated for each patient using a standard scoring approach and Poisson regression was used for identifying variables associated with the ARS.', 'Patients with an ARS >or= 3 had a lower eGFR (p = 0.012) and were receiving more non-anticholinergic drugs (p < 0.001) than patients with an ARS < 3. In addition to being prescribed more anticholinergic drugs, patients with ARS >or= 3 were prescribed high doses of these drugs more often than patients with ARS < 3 (41.3% vs. 26.9%, p = 0.034). A higher number of non-anticholinergic drugs (p < 0.001), a lower serum albumin concentration (p = 0.014), and a lower eGFR (p = 0.012) were independently associated with a higher ARS.


Output: Are hypoalbuminaemia and impaired renal function associated with increased anticholinergic drug prescribing?