Given a passage, 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: Various techniques and devices have been proposed for tricuspid valve (TV) repair in patients with tricuspid regurgitation (TR). However, residual or recurrent TR is not uncommon occurring in 20% to 30% of patients. This study reports first experiences with a new three-dimensional annuloplasty ring.', 'We retrospectively reviewed 200 consecutive patients who underwent TV repair for functional TR with the Contour 3D annuloplasty ring (Medtronic, Minneapolis, MN) from December 2010 to February 2013 at our institution. The follow-up is 98% complete (mean 1.0 ±\xa00.7 years; cumulative total 189 patient-years).', 'Mean age was 70.4 ± 9.1 years and the median logistic European system for cardiac operative risk was 7%. Sixty-nine percent of the patients were in New York Heart Association class III/IV. Echocardiography documented moderate or severe TR in 97.5% of the patients, with a mean annulus diameter of 45.1 ± 4.9 mm; 93.5% of the patients underwent a combined procedure, and 20.5% an urgent or emergent operation. The 30-day mortality was 6%. The preoperative TR grade was reduced from 2.45 ± 0.53 to 0.77 ± 0.54 (p < 0.001). At hospital discharge residual II TR or greater was present in 4.3% of the patients. Freedom from recurrent II TR or greater at 2\xa0years was 90.9% ± 4.2% and freedom from TV-related reoperations at 2 years was 98.5% ± 1.0%. No case of\xa0ring dehiscence occurred. Fourteen patients (7%) required a permanent pacemaker implantation for atrioventricular block.

Output: Does early experience with a new three-dimensional annuloplasty ring for the treatment of functional tricuspid regurgitation?


Input: Consider Input: Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.', 'Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.', 'We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.

Output: Does wNT5A induce release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells?


Input: Consider Input: Telomerase, a ribonucleoprotein enzyme mainly consisted of a catalytic protein subunit human telomerase reverse transcriptase (hTERT) and a human telomerase RNA component, is responsible for maintaining telomeres. Telomerase over-expression correlates significantly with tumors and is a prognostic marker. However, telomerase over-expression in breast cancers and the effect of telomerase inhibition as a candidate cancer therapy are unknown.', 'We used the dominant-negative mutant of hTERT (DN-hTERT) to inhibit telomerase activity on human breast adenocarcinoma cell line MCF-7 by transfection. Telomeric repeat amplification protocol assays and real-time quantitative RT-PCR were performed to investigate telomerase activity as well as expression of hTERT. Telomere length was measured by the flow-fluorescence in situ hybridization assay. Cell proliferation was assessed by the WST-8 assay, and apoptosis was evaluated by flow cytometry. The tumor formation ability of MCF-7 cells was investigated by transplanting cells subcutaneously into BALB/c nude mice.', 'Ectopic expression of DN-hTERT caused dramatically inhibition of telomerase activity and reduction of telomere length. Telomerase inhibition induced growth arrest and apoptosis of MCF7 cells in vitro and loss of tumorigenic properties in vivo.


Output: Does inhibition of telomerase activity by dominant-negative hTERT retard the growth of breast cancer cells?