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: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.", 'Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.

Output: Are plasma PCSK9 levels significantly modified by statins and fibrates in humans?


Input: Consider Input: The objective in lung transplantation is to prolong life, but the survival effect in patients with chronic obstructive pulmonary disease (COPD) or alpha1-anti-trypsin deficiency emphysema is still unresolved. This study assesses the impact of diagnosis, single-lung transplantation (SLT) vs bilateral lung transplantation (BLT) and timing of transplantation on survival in a national cohort.', 'In 219 consecutive patients accepted onto the lung transplantation waiting list in Norway, 1990 to 2003, we assessed predictors of death: (1) on the waiting list; (2) <or=90 days after transplantation; and (3) >90 days after transplantation. For each period we used Cox regression, including age, gender, diagnosis, baseline pulmonary function tests, cardiac catheterization data, exercise capacity and transplant type, as potential predictors. Survival benefit was assessed graphically by combining adjusted survival curves after transplantation with the curve for those waiting, modeling transplantation after 6, 12 or 24 months.', 'Mean patient age was 49 years (SD 10), with 55% women. High forced expiratory volume in 1 second (FEV(1)) percentage predicted death on the waiting list. Diagnoses other than COPD/emphysema and receiving SLT were associated with death <or=90 days after transplantation. Only low forced vital capacity (FVC) percentage predicted death >90 days after transplantation. In COPD/emphysema, there was no clear survival benefit from BLT or SLT. For patients in the "Other" group, the data suggest a survival benefit from BLT.

Output: Is lung transplantation in patients with chronic obstructive pulmonary disease in a national cohort without obvious survival benefit?


Input: Consider Input: Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics.', 'We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism.', "After 7 days of culture, compared with those cultured with cytokines alone (3.25 ± 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 ± 0.61 (P = 0.003) and 4.06 ± 0.43 (P = 0.025)-fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38- cells than stroma-free culture (156.17 ± 21.32 versus 79.12 ± 19.77-fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% ± 11.0% versus 16.0% ± 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo.


Output: Do endothelial progenitor cells promote efficient ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells?