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: 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\u2009>\u200910% 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\u2009=\u2009.0004) and OS (P\u2009≤\u2009.0001). 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.

A: Does next-generation sequencing survey of biliary tract cancer reveal the association between tumor somatic variants and chemotherapy resistance?
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Q: Context: The fruits of Vitex rotundifolia L. are widely used to treat inflammation of the airway in Traditional Chinese medicine. Previous studies found that casticin, isolated from Vitex rotundifolia, could induce apoptosis of tumor cells. In this study, we evaluated the anti-inflammatory effects of casticin and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated macrophages.', 'RAW264.7 cells were pretreated with various concentrations of casticin (0.3-10μM), and then treated with LPS to induce inflammation. We assayed the levels of proinflammatory cytokines and prostaglandin E2 (PGE2) using ELISA, and examined the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 by Western blot. We also investigated the anti-inflammatory molecular mechanism by analyzing inflammatory-associated signaling pathways, including the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.', 'We found casticin inhibited the levels of nitric oxide and PGE2, and decreased the production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α). In addition, iNOS and COX-2 expression levels were suppressed and casticin increased HO-1 and Nrf2 production in a concentration-dependent manner. Furthermore, casticin significantly inhibited NF-κB subunit p65 proteins in the nucleus and decreased Akt and MAPK activation.
Answer: These results suggest that the anti-inflammatory effect of casticin is due to inhibition of proinflammatory cytokines and mediators by blocking the NF-κB, Akt, and MAPK signaling pathways.

A: Does casticin inhibit COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages?
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Q: Context: There have been conflicting results from studies to determine whether factors unrelated to endoscopist skill, such as fatigue, affect the quality of screening colonoscopy. We studied the effects of human and system factors on screening colonoscopy withdrawal time and likelihood of detecting an adenoma in a large cohort of patients.', 'We performed a retrospective analysis of operation and quality improvement data in colonoscopies performed at single academic medical center from November 2012 through February 2014. We collected data from the Northwestern Medicine Enterprise Data Warehouse on endoscopy procedure reports, patient demographics, and pathology reports of all patients undergoing endoscopy. We identified all screening colonoscopies during the study period and determined whether an adenoma was identified in each screening colonoscopy procedure. Our study included data from 7004 screening colonoscopies of patients 50-75 years old performed by endoscopists who performed at least 100 screening colonoscopies during the study period (n = 18).', 'Approximately 27% of procedures began on time; the median colonoscope insertion time was 5.9 minutes (interquartile range, 4.0-8.6). In multivariable logistic regression analysis adjusting for covariates and endoscopist-level clustering, adenoma detection was not associated with procedure delay (P = .48), hour of day (P = .40), or performing the second of 2 colonoscopy blocks in 1 day (P = .88). Adenoma detection was associated with insertion time overall (P = .006), but there was no consistent directional relationship across insertion quintiles.
Answer: Procedure delays and measured factors associated with fatigue, including time of day and multiple procedure blocks, do not reduce the odds of detecting an adenoma. Adenoma detection varies widely among providers, so efforts to improve adenoma detection should focus mainly on optimizing physician skill.

A:
Are procedure Delays and Time of Day Associated With Reductions in Quality of Screening Colonoscopies?
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