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: The ability to achieve significant donor engraftment without fully myeloablative conditioning has revolutionized allogeneic stem cell transplantation. These nonmyeloablative approaches may allow extension of this potentially curative modality to an increasing number of patients including those with non-malignant diseases. Although a number of regimens have been explored, the optimal means of conditioning has not been determined.', 'We previously demonstrated that rapamycin (RAPA) has the ability to promote T-cell tolerance even in the presence of costimulation. In the current study, we examine the ability of rapamycin or the calcineurin inhibitor cyclosporine A (CSA) to promote chimerism in a murine haploidentical bone marrow transplantation model. Mice were conditioned with 300 cGy and received either RAPA at 3 mg/kg/day IP, CSA at 20 mg/kg/day IP, or no immunosuppression starting on the day before the transplant and continued for 4 weeks.', 'There was no apparent toxicity, and animals maintained normal blood counts throughout. More importantly, long-term macrochimerism was observed only in the RAPA-treated group.
Answer: These results establish a simple, nontoxic, irradiation-based regimen that facilitates engraftment without ablation. This strategy may prove useful in nonmalignant disorders such as hemoglobinopathies in which moderate levels of donor chimerism could prove curative.

Output: Does low-dose radiation plus rapamycin promote long-term bone marrow chimerism?


Input: Consider Input: Context: The normal anterior translation of the articular surface of the distal humerus with respect to the humeral diaphysis facilitates elbow flexion. We hypothesize that there is a correlation between anterior translation of the distal humeral articular surface and flexion after open reduction and internal fixation (ORIF) of a fracture of the distal humerus.', 'Two independent observers evaluated 141 lateral radiographs of patients more than 6 months after fracture of the distal humerus and 155 lateral radiographs of patients without injury of the distal humerus. The distance between the most anterior point of the distal humerus articular surface, perpendicular to the humeral shaft, from the anterior border of the distal part of the humeral diaphysis, was measured on lateral radiographs as a percentage of the width of the humeral shaft.', 'The technique of measuring anterior translation of the distal humeral articular surface had good intra- and interobserver reliability. The most anterior point of the distal humeral articular surface lies an average of 11.7 mm (range, 6.8 to 17.0 mm) in front of the most anterior border of the humeral shaft in normal distal humeri, which represents 62% of the humeral shaft diameter (range, 33% to 91%). There was a limited but significant correlation between flexion and anterior translation as a percentage of the humeral shaft diameter in distal humeri after fracture that was maintained in multivariable statistical models.
Answer: Using a reproducible technique for measuring anterior translation of the distal humerus, there was a correlation between anterior translation of the distal humeral articular surface and elbow flexion after ORIF. Although the weakness of the correlation emphasizes that limitation of elbow flexion after ORIF of a distal humerus fracture is multifactorial, reduced anterior translation of the distal humeral articular surface might be a contributing factor.

Output: Is loss of anterior translation of the distal humeral articular surface associated with decreased elbow flexion?


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?