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: High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.', 'In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3+/-8.9 kg/m(2)) and 20 healthy lean subjects (BMI 22.1+/-1.8 kg/m(2)), UFF and UFE, tetrahydrocortisol (THF), 5alpha-tetrahydrocortisol (5alpha-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5alpha-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.', 'In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11beta-HSD2 activity after adjustment for gender and BMI (r=0.47, p=0.0002 and r=0.31, p=0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p=0.4 and p=0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r=0.58, p=0.01 and r=0.55, p=0.02, respectively), whereas urine volume was not associated with 11beta-HSD2 activity after appropriate adjustment (p=0.3).

Output: Is urinary free cortisone , but not cortisol , associated with urine volume in severe obesity?


Input: Consider Input: To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.', 'Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.', 'The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor alpha could stimulate the expression of CCL13 in synovial fibroblasts; IL-1beta was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.

Output: Does induction of CCL13 expression in synovial fibroblasts highlight a significant role of oncostatin M in rheumatoid arthritis?


Input: Consider Input: Exposure to hypoxia has been suggested to acutely alter glucose regulation. However, the effects of successive exposure to moderate hypoxia on postprandial glucose regulation and substrate oxidation pattern after multiple meals have not been elucidated.', 'We examined the effects of successive exposure to moderate hypoxia on metabolic responses and substrate oxidation pattern.', 'Eight healthy men (21.0\u2009±\u20090.6\xa0yrs, 173\u2009±\u20092.3\xa0cm, 70.6\u2009±\u20095.0\xa0kg, 23.4\u2009±\u20091.1\xa0kg/m(2)) completed two experimental trials on separate days: a rest trial under normoxic conditions (FiO2\u2009=\u200920.9%) and a rest trial under hypoxic conditions (FiO2\u2009=\u200915.0%). Experimental trials were performed over 7\xa0h in an environmental chamber. Blood and respiratory gas samples were collected over 7\xa0h. Standard meals were provided 1\xa0h (745\xa0kcal) and 4\xa0h (731\xa0kcal) after entering the chamber.', 'Although each meal significantly increased blood glucose and serum insulin concentrations (P\u2009<\u20090.05), these responses did not differ significantly between the trials. There were no significant differences in areas under the curves for glucose or insulin concentrations over 7\xa0h between the trials. No significant differences were observed in blood lactate, serum cortisol, free fatty acid, or glycerol concentrations over 7\xa0h between the trials. The oxygen consumption ( [Formula: see text]) and carbon dioxide production ( [Formula: see text]) 3\xa0h after entering the chamber were significantly higher in the hypoxic trial than in the normoxic trial (P\u2009<\u20090.05). However, the differences did not affect respiratory exchange ratio (RER). The average values of [Formula: see text], [Formula: see text], and RER did not differ between the trials.


Output: Does successive exposure to moderate hypoxia affect glucose metabolism and substrate oxidation in young healthy men?