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: Transcatheter aortic valve implantation (TAVI) without predilatation has fewer procedural steps and thereby potentially fewer complications. This has been demonstrated for the antegrade transapical access; however, whether TAVI can be safely performed without predilatation using the retrograde transfemoral route is unknown.', 'We postulated that TAVI is feasible with a balloon-expandable device without predilatation using the retrograde transfemoral route.', 'Twenty-six consecutive patients with stenosis of the native aortic valve (AV) undergoing transfemoral TAVI with the Edwards SAPIEN XT prosthesis without predilatation were enrolled in this retrospective study and compared with 30 patients treated previously with predilatation.', 'The procedure was successfully performed in all 26 patients, irrespective of the AV area and the extent of AV calcification. At baseline mean AV area, mean AV gradient, and median left ventricular ejection fraction were 0.7 ± 0.2 cm(2) , 36.0 ± 17.3 mm Hg, and 55.0% (interquartile range [IQR], 35.0-60.0], respectively; prior to discharge these values were 1.7 ± 0.3 (P < 0.001), 9.8 ± 6.1 mm Hg (P < 0.001), and 57.5% (IQR, 38.7-60.0) (P = not significant). Postdilatation was required in 3 patients due to aortic regurgitation > 2°; this was reduced by the procedure to < 2° in all cases. Radiation dose and amount of contrast dye were significantly reduced in comparison with the predilatation group. No periprocedural neurological adverse events occurred. Mortality at 30 days was 0%.
Answer: TAVI without predilatation using the transfemoral Edwards SAPIEN XT valve is feasible and safe. Larger studies are required to further evaluate this approach.

Output: Is transfemoral aortic valve implantation of Edwards SAPIEN XT without predilatation feasible?


Input: Consider Input: Context: Left ventricular hypertrophy (LVH) is common in patients with autosomal dominant polycystic kidney disease (ADPKD). Although insulin resistance contributes to cardiac hypertrophy, the relationship between insulin resistance and LVH in patients with ADPKD has not been previously studied.', 'We performed M-mode and color Doppler echocardiography on 176 family members (106 patients and 70 healthy relatives) from 16 families with polycystic kidney disease type 1 (PKD1). Left ventricular mass index (LVMI) was calculated using the Penn equation and corrected for body surface area. Fasting insulin and glucose concentrations were measured and insulin resistance was evaluated by means of the homeostasis model assessment.', 'In multivariate regression analysis, insulin resistance was significantly associated with LVMI in healthy relatives (P < 0.01) and patients with PKD1 (P < 0.05) independent of age, weight, systolic blood pressure, and albuminuria.
Answer: Insulin resistance is associated with LVMI in patients with PKD1 independently of other factors known to increase LVMI.

Output: Is insulin resistance related to left ventricular hypertrophy in patients with polycystic kidney disease type 1?


Input: Consider Input: Context: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma.', 'Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan.', 'miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx-efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice.
Answer: Taken together, our findings provide the proof of concept that LNA-i-miR-221 can reverse melphalan resistance in preclinical models of multiple myeloma, providing the framework for clinical trials to overcome drug resistance, and improve patient outcome in multiple myeloma.


Output: Does a 13 mer LNA-i-miR-221 Inhibitor restore Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells?