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.

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


[Q]: Context: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear.', 'The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu.', 'DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response.', 'Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression.
Answer: Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.
[A]: Does tollip SNP rs5743899 modulate human airway epithelial responses to rhinovirus infection?


[Q]: Context: To compare prognosis of clival chordomas with different dural penetration, and establish the relationship between dural penetration and platelet-derived growth factor receptor (PDGFR)-β signaling pathway.', 'Tumors in Type I (33 cases) showed limited dural penetration, while those in Type II (34 cases) had more serious dural penetration. Cox multivariate regression analysis was used to analyze risk factors affecting survival. Kaplan-Meier analysis measured overall survival (OS) and progression-free survival (PFS). To determine relationship between dural penetration and PDGFR-β signaling, expression of PDGFR-β, Akt, mammalian target of rapamycin (mTOR), and phosphatase and tensin homolog (PTEN) expression was compared using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting.', 'Total resection was achieved in nine cases in Type I and eleven in Type II. There were significant correlations between OS and dural penetration (P=0.032) and age (P=0.034). PFS correlated significantly with dural penetration (P=0.022), gender (P=0.001), and degree of resection (P=0.001). Mean OS in Type I was significantly longer than in Type II (P=0.046). Patients aged <55 years had longer OS than those aged ≥55 years (P=0.004). Total resection was correlated with longer PFS (P=0.011). Among patients with tumor totally resected, mean PFS in Type I was significantly longer than in Type II (P=0.007). Expression of PDGFR-β in Type II was higher than in Type I.
Answer: Clival chordomas have different degrees of dural penetration. Patients with chordomas with serious dural penetration have poorer prognosis. Higher expression of PDGFR-β is related to more serious dural penetration of clival chordomas.
[A]:
Are differences in dural penetration of clival chordomas associated with different prognosis and expression of platelet-derived growth factor receptor-β?