In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Q: Context: Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction.', 'To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS).', 'PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test.', 'Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated proteinC, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma.\Question: Do histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells?

A: Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones.
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Q: Context: To assess how different imputation methods used to account for missing variance data in primary studies influence tests of heterogeneity and pooled results from a meta-analysis with continuous outcomes.', 'Point and variance estimates for changes in serum creatinine, glomerular filtration rate, systolic blood pressure, and diastolic blood pressure were variably reported among 48 primary longitudinal studies of living kidney donors (71%-78% of point estimates were reported, 8%-13% of variance data were reported). We compared the results of meta-analysis, which either were restricted to available data or used four methods to impute missing variance data. These methods used reported P-values, reported nonparametric summaries, results from other similar studies using multiple imputation, or results from estimated correlation coefficients.', 'Significant heterogeneity was present in all four outcomes regardless of the imputation methods applied. The random effects point estimates and 95% confidence intervals varied little across imputation methods, and the differences were not clinically significant.\Question: Do imputing variance estimates alter the conclusions of a meta-analysis with continuous outcomes : a case study of changes in renal function after living kidney donation?

A: Different methods to impute the variance data in the primary studies did not alter the conclusions from this meta-analysis of continuous outcomes. Such reproducibility increases confidence in the results. However, as with most meta-analyses, there was no gold standard of truth, and results must be interpreted judiciously. The generalization of these findings to other meta-analyses, which differ in outcomes, missing data, or between-study heterogeneity, requires further consideration.
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Q: Context: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans.", 'Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation.', 'Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells.\Question: Does single oral dose of maraviroc prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers?

A:
An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission.
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