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.

Input: Consider Input: Context: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.', 'Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms.', 'Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.
Answer: Mst1 knockout restores autophagy and protects against apoptosis in cardiomyocytes, en route to the rescue against DCM.

Output: Does mST1 coordinately regulate autophagy and apoptosis in diabetic cardiomyopathy in mice?


Input: Consider Input: 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.

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


Input: Consider Input: Context: The significance of high triglyceride levels as a risk factor for coronary heart disease is uncertain. We hypothesized that oral glucose tolerance test (OGTT) and certain novel markers may help to identify high-risk patients.', 'We recruited 80 subjects with severe hypertriglyceridemia (age 27-73 years) without clinical proteinuria and diabetes mellitus (DM) which were diagnosed by fasting glucose <126 mg/dL from Hyperlipidemia Clinic of National Taiwan University Hospital for this study. We applied OGTT to evaluate occult DM and homeostasis model assessment (HOMA)-insulin resistance (IR) score to evaluate insulin resistance, and the measurements of microalbuminuria as a marker of vascular damage. In addition, serum or plasma markers of inflammation and fibrinolysis, fasting glucose and insulin as well as traditional cardiovascular risk factors were also evaluated.', 'The serum level of triglyceride was higher in patients with microalbuminuria than in those without (14.1+/-5.7 vs. 9.6+/-3.9 mmol/L, p=0.025). Patients with microalbuminuria had higher fasting blood glucose and insulin, higher post-OGTT glucose and insulin, higher prevalence of newly developed diabetes mellitus (DM) (39% vs. 11%, p=0.007) and higher HOMA-IR (6.2+/-4.4 vs. 3.3+/-2.0, p<0.001). Among all the inflammatory and fibrinolytic markers, only soluble intercellular adhesion molecule showed significant different between these two groups. Multiple logistic regression analysis showed that among the serum markers, only HOMA-IR level was significantly related to microalbuminuria.
Answer: HOMA-IR is the major determinant for microalbuminuria in patients with severe hypertriglyceridemia. Impaired glucose metabolism is evident in patients with both severe hypertriglyceridemia and microalbuminuria.


Output: Is insulin resistance the major determinant for microalbuminuria in severe hypertriglyceridemia : implication for high-risk stratification?