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.

[Q]: Context: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.', 'To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.', 'Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.', 'Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P\xa0<\xa00·01). Multiple hierarchical linear regression analyses showed a statistically significant (P\xa0<\xa00·01) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P\xa0<\xa00·05) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.
Answer: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.
[A]: Is itching a significant problem and a mediator between disease severity and quality of life for patients with psoriasis : results from a randomized controlled trial?


[Q]: Context: To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents.', 'This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17\xa0years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30\xa0had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD.', 'The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected.
Answer: Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD.
[A]: Is amino Acid Metabolism Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted , High Resolution Metabolomics Study?


[Q]: Context: Circulatory shock results in hypoxia/reoxygenation processes that lead to the release of reactive oxygen species, endothelial injury, and multiple organ failure. Previous data suggest that beta2-adrenergic agonists prevent endothelial dysfunction. The study aimed at determining whether the beta2-adrenergic agonist formoterol protects endothelial cells against hypoxia/reoxygenation injury in vitro.', 'Prospective controlled trial.', 'University hospital research laboratory.', 'Cultured human umbilical vein endothelial cells (HUVECs).', "Confluent HUVECs were sealed in a flow-through chamber mounted on an inverted microscope and perfused with a constant flow of Krebs medium. After 1 hr of equilibration, HUVECs underwent 2 hrs of hypoxia and 1 hr of reoxygenation. Cell death at the end of reoxygenation and reactive oxygen species formation were assessed with fluorescent probes propidium iodide and 2',7'-dichlorodihydrofluorescein diacetate, respectively. The effects of the beta2-adrenergic agonist formoterol, the beta2-adrenergic antagonist ICI 118,551 and the nitric oxide synthase inhibitor L-NNA were investigated. Statistical analysis was performed with analysis of variance followed by post hoc Fisher's test.", 'Hypoxia/reoxygenation increased cell death (hypoxia/reoxygenation 29 +/- 4% vs. control 1 +/- 5%, p < .05) and endothelial reactive oxygen species production (hypoxia/reoxygenation 126 +/- 4% vs. control 108 +/- 4%, p < .05). Formoterol reduced cell death in a concentration-dependent manner (EC95 = 10 mol/L) and reduced endothelial reactive oxygen species production (hypoxia/reoxygenation + formoterol EC95 109 +/- 4% vs. hypoxia/reoxygenation 126 +/- 4%, p < .05). When added to formoterol EC95, ICI 118,551 and L-NNA abolished the formoterol-induced cell protection and reduced reactive oxygen species production.
Answer: These results indicate that formoterol reduces endothelial cell death and reactive oxygen species production in this in vitro hypoxia/reoxygenation model. These effects are beta2-adrenergic specific and are partially mediated by nitric oxide synthase.
[A]:
Does beta2-adrenergic agonist protect human endothelial cells from hypoxia/reoxygenation injury in vitro?