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: Although Alzheimer's disease (AD) is associated with early death, its life expectancy differs greatly between patients. A better understanding of this heterogeneity may reveal important disease mechanisms underlying the malignancy of AD. The aim of this study was to examine the relation between AD pathologies and early death in AD caused by dementia.", 'At a memory clinic, 247 referred consecutive patients with AD were monitored during 12.6\u2009±\u20091.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (Aβ) pathology (APOE genotype, cerebrospinal fluid (CSF) Aβ42) tau pathology (CSF phosphorylated tau and total tau), cerebrovascular pathology (white-matter lesions and CSF/serum albumin ratio), neuroinflammatory pathology (CSF soluble vascular cell adhesion molecule-1, sVCAM-1), frontal, temporal, and central brain atrophies, global cognition, sex, and age. Comorbidities and medications also were analyzed. All continuous variables were transformed to z scores to compare hazard ratios (HRs) and 95% confidence intervals (CIs).', 'At follow-up, 89% of the patients had died. The mean survival time was 6.4\u2009±\u20093.0 years. The AD pathology that independently predicted an early death caused by dementia was cerebral inflammation (sVCAM-1; HR, 1.32; 95% CI, 1.07-1.64). Other independent predictors were lower global cognition (HR, 0.51; 95% CI, 0.43-0.61), frontal atrophy (HR, 1.38; 95% CI, 1.12-1.70), and medial temporal atrophy (HR, 1.23; 95% CI, 1.02-1.49). When examining death caused by dementia and related causes (vascular diseases and infections), age (HR, 1.23; 95% CI, 1.04-1.46) and cerebrovascular pathology (white-matter lesions: HR, 1.17; 95% CI, 1.01-1.36; and CSF/serum albumin ratio: HR, 1.16; 95% CI, 1.001-1.34) were also significant risk factors in addition to the previous variables. No comorbidity or medication was significant in the specific-cause models.
Answer: This is the first study to link neuroinflammation independently to early death in AD and, hence, a rapidly progressing disease. Frontal and medial temporal atrophies and low cognition were also significant predictors. These are probably downstream biomarkers that reflect neuronal degeneration and late-stage disease. Our results suggest that inflammation, and not amyloid or tau pathology, is an independent underlying mechanism in the malignancy of AD.

Output: Is cerebral inflammation an underlying mechanism of early death in Alzheimer 's disease : a 13-year cause-specific multivariate mortality study?


Input: Consider Input: Context: Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal plant Buxus microphylla, has been found to be effective to treat cardiac insufficiency, arrhythmias and coronary heart disease. In the present study, we investigated the effects of CVB-D on the inflammatory responses in lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the underlying mechanisms.', 'Murine macrophage cell line RAW264.7 cells were incubated in the presence of LPS (0.1 μg/mL) for 24 h. The cell viability was measured using MTT assay. The release of NO and cytokines were detected using the Griess test and ELISA, respectively. The mRNA and protein levels were determined using RT-PCR and Western blot, respectively. Reporter gene assays were used to analyze the transcriptional activity of NF-κB.', 'Treatment of RAW264.7 cells with CVB-D (25-300 μmol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 μmol/L) concentration-dependently decreased NO release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in inhibition of NO production was 144 μmol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1β and IL-6 in LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7 cells, but did not affect the activation of NF-κB and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 μmol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.
Answer: CVB-D exerts anti-inflammatory effects in LPS-stimulated murine macrophages in vitro at least in part by blocking the JAK-STAT signaling pathway. The anti-inflammatory actions of CVB-D may contribute to its cardioprotection.

Output: Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?


Input: Consider Input: Context: To demonstrate the role of RpoE during the later stage of hyperosmotic stress in Salmonella.', 'Expressions of SPI-1 and SPI-2 under hyperosmotic stress for 120 min were investigated by a microarray, and the invasion and intracellular survival of wild-type and ΔrpoE strains were compared. The global differential expression of bacterial proteins between the wild-type and ΔrpoE strains was examined after 120 min of hyperosmotic stress.', 'SPI-1 and SPI-2 were repressed, and the invasion and intracellular survival were defected in the ΔrpoE strain. Thirteen bacterial-associated proteins and 11 secreted proteins differed significantly between the wild-type and ΔrpoE strains.
Answer: RpoE may promote invasion and intracellular survival by regulating the expression of SPI-1 and SPI-2.


Output: Does rpoE promote invasion and intracellular survival by regulating SPI-1 and SPI-2 in Salmonella enterica serovar Typhi?