TASK DEFINITION: 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.
PROBLEM: Context: We aimed to investigate whether and how the total flavonoid extracts (TFE) from Inula britannica L. block neointimal hyperplasia induced by balloon injury in rats.', 'Rats were administered orally TFE doses of 12.5, 25 and 50 mg/kg/d by gastric gavage from 3 days before balloon injury to 14 days after the injury. The ratio of intima (I) to media (M) thickness (I/M) in carotid arteries was examined by morphological analyses. The MDA content and SOD activity in plasma were measured. The O(2)(-) production in vascular tissues was detected in situ. The expression of p47(phox) in carotid arteries was analyzed by Western blot analysis and immunohistochemistry.', 'The rats treated with TFE 50 mg/kg/d showed a reduction in neointimal hyperplasia, and the ratio of I/M of balloon injured-carotid arteries was significantly reduced by over 70% after TFE treatment, compared with the injured group. The inhibitory effect of TFE on neointimal hyperplasia was almost consistent with that of atorvastatin, a positive control. The plasma SOD activity was obviously increased by TFE treatment (P<0.01), while plasma MDA production was markedly decreased by TFE treatment (P<0.05). On day 14 after balloon injury, the carotid arteries showed an increase in O(2)(-) production that was most evident in the neointimal and medial layer of the vessel. Thus, TFE significantly inhibited injury-induced O(2)(-) production and p47(phox) expression in carotid arteries.
Answer: Our results suggest that TFE inhibit the neointimal hyperplasia after balloon injury, at least partly, by suppressing oxidative-stress generation.

SOLUTION: Do flavonoids from Inula britannica L. inhibit injury-induced neointimal formation by suppressing oxidative-stress generation?

PROBLEM: Context: Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.', 'Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).', 'When genes with an incidence>10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P=.0004) and OS (P.0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.
Answer: In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. ©️ 2016 American Cancer Society.

SOLUTION: Does next-generation sequencing survey of biliary tract cancer reveal the association between tumor somatic variants and chemotherapy resistance?

PROBLEM: Context: To evaluate whether the presence of mucinous differentiation influences histopathologic findings, stage distribution, or rate of recurrence among women with grade 1, endometrioid type, endometrial carcinoma.', 'This was a retrospective cohort study of all patients with grade 1, endometrioid type, endometrial carcinoma between January 2005 and December 2012. Patients were separated by the presence or absence of mucinous differentiation and then compared.', 'Of 655 patients, mucinous differentiation was present in 137 (20.9%) and absent in 518 (79.1%) patients. Compared to the group without mucinous differentiation, the group containing mucinous differentiation was older at diagnosis (mean: 61.1 vs. 58.5 years, OR, 95% CI; 1.03, 1.01-1.05) and more likely to have myometrial invasion (61.3% vs. 51.5%, OR, 95% CI; 1.49, 1.01-2.19). Additional histopathologic findings including: tumor size, cervical stromal invasion, adnexal involvement, LVI and/or the presence of positive lymph nodes were similar between groups. Mucinous differentiation did not affect stage distribution, as most patients were stage 1A (85.4% vs. 86.3%). The median PFS for the entire group has yet to be reached. The mean PFS for the entire study sample was 94.7 months. There was no difference in mean PFS when comparing the group with mucinous differentiation to the group without mucinous differentiation (98 vs. 93.4 months, p=0.07).
Answer: In the setting of grade 1, endometrioid type, endometrial carcinoma, mucinous differentiation is more common in older patients and is associated with an increased likelihood of myometrial invasion. However, stage distribution and risk of recurrence are not affected.

SOLUTION:
Does mucinous differentiation impact stage or risk of recurrence among patients with grade 1 , endometrioid type , endometrial carcinoma?