instruction:
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.
question:
Pirfenidone (5 methyl-1-phenyl-2(1H)-pyridone) is a novel anti-fibrotic agent, which has been shown to decrease collagen deposition in a variety of animal models in vivo, and recently in hepatic fibrosis also. At cellular level, we have recently demonstrated that pirfenidone is able to inhibit proliferation of hepatic stellate cells induced by platelet-derived growth factor, as well as collagen type I accumulation and alpha1(I) procollagen mRNA expression.', 'To evaluate if pirfenidone maintains its anti-fibrotic properties also when administered after the induction of hepatic damage and to further investigate the molecular mechanisms leading to the anti-fibrotic effect of pirfenidone.', 'Rats treated with dimethylnitrosamine (10 mg/kg) for 5 weeks received a liquid diet containing 0.5% pirfenidone starting from the third week. Pirfenidone treatment reduced the degree of liver injury, as determined by alanine aminotransferase values and necro-inflammatory score, which was associated with reduced hepatic stellate cells proliferation and collagen deposition. Treatment with dimethylnitrosamine increased transcripts levels for transforming growth factorbeta1, procollagen alpha1(I), tissue inhibitors of metalloproteinase-1 and matrix metalloproteinase-2 by 7-, 7-, 4- and 15-fold, respectively. Pirfenidone administration downregulated elevated levels of those transcripts by 50-60%, and this was associated with a 70% reduction in collagen deposition.
answer:
Is the anti-fibrotic effect of pirfenidone in rat liver fibrosis mediated by downregulation of procollagen alpha1 ( I ) , TIMP-1 and MMP-2?

question:
Hostile neck anatomy is assumed to be associated with increased surgical risk for patients undergoing carotid endarterectomy (CEA) and is often considered a reason to choose carotid stenting or medical management. This retrospective case-control study evaluated whether, and how much, anatomically hostile necks represent a condition of higher surgical risk of early and late mortality and major or minor morbidity.', 'The data for 966 homogeneous CEA patients was prospectively entered in a computer database. Seventy-seven had a hostile neck anatomy due to previous oncologic surgery or neck irradiation, restenoses after CEA, high carotid bifurcation, or bull-like and inextensible neck. A case-control matched-pair cohort study considered sex, age (5-year intervals), and year of operation. Regional anesthesia was used for all operations for atherosclerotic stenosis >or=70%, conforming to the European Carotid Surgery Trial (ECST) in symptomatic and asymptomatic patients, at a single center and by one surgeon or under his direct supervision.', 'The hostile neck patients and the control group were matched for age, sex, carotid-related symptoms, degree of stenoses, and main risk factors for cardiovascular diseases. Intraoperative variables were substantially equivalent in the two groups; however, procedure length and clamping time were, respectively, about 22 minutes (P = .0001) and 7 minutes longer (P = .01) in the hostile neck group. Rates of postoperative mortality and neurologic events were equivalent. Peripheral nerve lesions were multiple and significantly more frequent in the hostile neck patients (21% with >or=1 cranial nerve lesion vs 7% of controls, P = .03), yet all were transient and limited to a few months. The subgroups of patients with hostile neck, restenoses, and bull-like inextensible necks required the longest operative and clamping time, and those with bull-like and high bifurcation had the most frequent cranial nerve dysfunctions. At the respective follow-up of 47 and 45 months, survival curves (P = .48) and the incidence of restenoses and fatal and nonfatal strokes were similar (5 and 4, respectively).
answer:
Does the hostile neck increase the risk of carotid endarterectomy?

question:
To demonstrate bioequivalence of linagliptin/metformin fixed-dose combination (FDC) tablets and the corresponding combination of individual tablets taken together, i.e., free-pill (FP) treatment.', 'Three dosing combinations were evaluated in three separate randomized studies: linagliptin 2.5 mg with 500 mg, 850 mg, or 1,000 mg metformin. These studies used a prospective, open-label, randomized, two-way crossover design to evaluate bioequivalence in healthy volunteers (n = 287). After an overnight fast, participants received an FDC tablet once, and on a separate visit received the corresponding FP treatment. The two possible treatment sequences (FDC/FP and FP/FDC) were randomly allocated to the participants. A washout period of 35 days separated the two study treatments. The primary endpoints were maximum plasma concentration (Cmax) of linagliptin and metformin, area under the plasma concentration time curve from 0 to 72 hours (AUC0-72) for linagliptin, and from 0 to infinity (AUC0-inf) for metformin.', 'The 90% confidence intervals of the adjusted geometric mean ratios of Cmax and AUC (calculated as FDC/ FP) were within the bioequivalence acceptance limits of 80 - 125%. The number of participants reporting at least one adverse event following FDC treatments was comparable to, or less than, that following FP treatments. Evaluation of vital signs and clinical laboratory tests revealed no safety issues.
answer:
Is linagliptin fixed-dose combination with metformin bioequivalent to co-administration of linagliptin and metformin as individual tablets?