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: 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.
Answer: These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.

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

Input: Consider Input: Context: To assess the accuracy of the clinically estimated blood loss (EBL) when compared with the actual blood loss (ABL) in replacement surgeries.', "This prospective study was done in Sri Ramachandra Medical Centre from April 2011 to April 2013. Altogether 140 patients undergoing total hip replacement or total knee replacement were included with the inclusion criteria being patients with haemoglobin higher than 100 g/ml and coagulation profile within normal limits. Exclusion criteria were intake of anti-platelet drug or anti-coagulant, bleeding disorders, thrombotic episode, and haematological disorders. There were 65 men and 75 women. In this study, the consultants were free to use any clinical method to estimate the blood loss, including counting the blood-soaked mops and gauze pieces (estimating the volume of blood carried in all the mops and gauzes), measuring blood lost to suction bottles and blood in and around the operative field. The ABL was calculated based on a modification of the Gross's formula using haematocrit values.", 'In 42 of the 140 cases, the EBL exceeded the ABL. These cases had a negative difference in blood loss (or DIFF-BL<0) and were included in the overestimation group, which accounted for 30% of the study population. Of the remaining 98 cases (70%), the ABL exceeded the EBL. Therefore they were put into the underestimation group who had a positive difference in blood loss (DIFF-BL>0). We found that when the average blood loss was small, the accuracy of estimation was high. But when the average blood loss exceeded 500 ml, the accuracy rate decreased significantly. This suggested that clinical estimation is inaccurate with the increase of blood loss.
Answer: This study has shown that using clinical estimation alone to guide blood transfusion is inadequate. In this study, 70% of patients had their blood loss underestimated, proving that surgeons often underestimate blood loss in replacement surgeries.

Output: Do surgeons often underestimate the amount of blood loss in replacement surgeries?

Input: Consider Input: Context: The exact role Entamoeba histolytica cysteine proteases play in overcoming the colonic mucus barrier, as a prerequisite to epithelial cell disruption, is not known. Herein, we determined whether E histolytica trophozoites expressing the antisense transcript to cysteine protease 5 (EhCP5) could degrade colonic mucin and destroy epithelial cells.', 'Cysteine protease-deficient amoebae were generated by antisense inhibition of EhCP5, and assayed for proteolytic activity against [(35)S]cysteine-labeled mucin from LS 174T, and HT-29F Cl.16E cells. Recombinant EhCP5 mucinase activity was also assessed. Disruption of an intact mucus barrier and epithelial cell invasion by amoebae were measured using high mucin producing LS 174T and HT-29 Cl.16E monolayers or Chinese hamster ovary (CHO) cells devoid of a mucus barrier.', 'Trophozoites with reduced cysteine protease activity were ineffective at degrading [(35)S]cysteine-labeled colonic mucin compared to wild-type amoebae by >60%. However, bioactive recombinant EhCP5 degraded >45% of purified native mucin, which was specifically inhibited by the cysteine proteinase (CP) inhibitor, E-64. Cysteine protease-deficient trophozoites could not overcome a protective intact mucus barrier and disrupt LS 174T or HT-29F Cl.16 cell monolayers; however, they readily adhere to and disrupt CHO monolayers devoid of a mucus barrier.
Answer: These findings unravel a central role for E histolytica CPs as key virulence factors in disrupting an intact mucus barrier in the pathogenesis of intestinal amoebiasis.
Output: Does antisense inhibition of Entamoeba histolytica cysteine proteases inhibit colonic mucus degradation?