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.

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.
Is amino Acid Metabolism Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted , High Resolution Metabolomics Study?

Context: To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT-UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end-stage renal disease (ESRD) have a higher incidence of UT-UC, but the relationship between early stages of CKD and characteristics of UT-UC are less well known.', 'The study included 267 patients with pathologically confirmed UT-UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30-60 (CKD stage 3) and <30 (CKD stage 4/5).', 'The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT-UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high-grade and high T stage UT-UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.
Answer: The aggressiveness of UT-UC increased with the severity of CKD, and this might have important clinical consequences.
Does the aggressiveness of urinary tract urothelial carcinoma increase with the severity of chronic kidney disease?

Context: Evidence suggests that induction of heme oxygenase-1 (HO-1) inhibits proliferation of vascular smooth muscle cells and intimal thickening after arterial injury, and therapeutic molecules induce HO-1. Probucol is the only oral drug that inhibits restenosis in humans and intimal thickening in animals, although its underlying mechanism remains unclear.', 'Aortas were harvested from New Zealand White rabbits fed normal or 0.75% (wt/wt) probucol-fortified chow, with or without endothelial denudation of the abdominal aorta on day 21, and analyzed for heme oxygenase and apoptosis. Uninjured aortas were harvested on day 21 and balloon-injured aortas on days 22 and 25. Probucol significantly increased mRNA of HO-1 assessed by real-time PCR and HO activity in aortas at all time points. Probucol also enhanced apoptosis of medial cells in the injured aorta, as evidenced by the TUNEL assay. Furthermore, probucol (100 micromol/L) increased HO-1 mRNA and HO activity when added to rabbit aortic smooth muscle cells (RASMCs) cultured in serum-free medium for 24 hours. Induction of HO-1 mRNA was inhibited by actinomycin D and was associated with inhibition of RASMC proliferation. This probucol-induced increase in HO-1 mRNA and inhibition of RASMC proliferation was prevented by the HO inhibitor Sn(IV) protoporphyrin or transfection with small interference RNA (siRNA) to knockdown HO-1, but not by inactive Cu(II) protoporphyrin or scrambled siRNA.
Answer: Probucol induces HO-1, and this contributes to the inhibition of vascular SMC proliferation. This novel finding may explain how probucol inhibits restenosis and highlights HO-1 as a target for therapeutic intervention against occlusive vascular disease.

Does probucol protect against smooth muscle cell proliferation by upregulating heme oxygenase-1?