TASK DEFINITION: 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.
PROBLEM: Despite the clinical efficacy of recombinant human erythropoietin (RHE) on chemotherapy-induced anemia, most cost-effectiveness studies have given unfavorable results.', 'To determine the cost of managing anemia in unselected patients receiving chemotherapy for lung cancer, and the efficacy and cost-effectiveness of RHE.', 'We constructed Markov models of two cohorts of patients who received (n=94) or did not receive (n=89) darbepoetin (one weekly injection when the hemoglobin level fell below 11 g/dl), focusing on changes in hemoglobin levels, transfusion requirements, anemia management costs, and the cost-effectiveness ratios of the two management strategies.', 'The use of RHE significantly reduced the proportion of patients needing transfusions (from 33.6% to 19.1%, p<0.05) and the number of red cell units used by transfusion (from 2.97+/-1.47 to 2.11+/-0.47, p<0.01). Markov modeling showed that the RHE strategy significantly increased the mean Hb level (13+/-0.5 g/dl versus 11.9+/-1g/dl, p<0.001), at the price of an increase in the main cost (respectively, US$ 1732+/-897 and 996+/-643; p<0.01). The cost-effectiveness ratio favored the RHE strategy (7.02 versus 9.04). Sensitivity analysis showed that the RHE strategy remained dominant in most situations.

SOLUTION: Is routine once-weekly darbepoetin alfa administration cost-effective in lung cancer patients with chemotherapy-induced anemia : a Markov analysis?

PROBLEM: The aim of the study was to determine whether medial meniscal substitution with a polyurethane scaffold (Actifit(®)) improves the outcome of medial meniscal-deficient varus knees undergoing open-wedge high tibial osteotomy.', 'Sixty patients with symptomatic varus knees those who underwent open-wedge high tibial osteotomies were prospectively studied. In 30 patients, the medial meniscus was left with a defect larger than 25 mm (Group M). An Actifit(®) device was implanted (Group A) in the remaining 30 patients. Patients were functionally evaluated with WOMET, IKDC and VAS. Patient satisfaction was graded from 0 (not satisfied) to 4 (very satisfied).', 'Both groups were comparable preoperatively. They had similar follow-up periods (31.2 months; range 24-47.5; n.s.). WOMET improved a mean of 53.4 ± 8.4 and 42.4 ± 17.2 points in Groups M and A, respectively (p = 0.002). IKDC improved a mean of 56.7 ± 12 and 50.3 ± 15.6 points in Groups M and A, respectively (n.s.). VAS dropped 5.9 ± 2.1 and 4.7 ± 2.8 points in Groups M and A, respectively (p = 0.006). Patient satisfaction averaged 3.3 ± 0.8 and 3.3 ± 1 in Groups M and A, respectively (n.s.).

SOLUTION: Does partial meniscus substitution with a polyurethane scaffold improve outcome after an open-wedge high tibial osteotomy?

PROBLEM: To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.', 'To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step "pop-in/pop-out" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation.

SOLUTION:
Does a novel two-step genome editing strategy with CRISPR-Cas9 provide new insights into telomerase action and TERT gene expression?