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 12.61.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (A) pathology (APOE genotype, cerebrospinal fluid (CSF) A42) 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 6.43.0 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?
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Q: Context: The endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining.', 'Out of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition.
Answer: We conclude that severe hypoxia confers a quiescent phenotype in hMSCs that is reflected by both the transcriptome profile and gene-specific changes of splicosome actions. The results reveal that severe hypoxia imposes markedly different patterns of gene regulation of MSCs compared with more moderate hypoxia. This is the first study to report hypoxia-regulation of AS in stem/progenitor cells and the first molecular genetic characterization of MSC in a hypoxia-induced quiescent immobile state.

A: Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?
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Q: Context: To investigate the associations between C-reactive protein (CRP), homocysteine levels, use of hormone therapy (HT) and other factors.', "A 12-year prospective study of 438 Australian-born women (Melbourne Women's Midlife Health Project), who at baseline were aged 45-55 years, had menstruated in the previous 3 months and were not taking HT. Fasting blood was collected in the 11th follow-up year for CRP, homocysteine, estradiol and follicle stimulating hormone (FSH) levels. Physical measurements and face-to-face interviews obtained information on health and lifestyle variables.", 'A total of 258 women (mean age 60 years) participated in the 11th follow-up year. Multiple regression analysis found that CRP levels were positively associated with body mass index (p < 0.001), HT use (p < 0.01), and negatively associated with statin use (p < 0.005) and exercising (p < 0.05). In postmenopausal women currently not using HT (n = 173) and after adjusting for body mass index, exercise and smoking, CRP was negatively associated with FSH levels (beta = -0.32, p < 0.05). Homocysteine levels were positively associated with smoking (p < 0.001) and negatively associated with HT use (p < 0.05).
Answer: In middle-aged Australian-born women, HT use was associated with increased CRP and decreased homocysteine levels. High CRP levels were also associated with high relative weight, low exercise levels and no statin medication.

A:
Are serum C-reactive protein and plasma homocysteine levels associated with hormone therapy use and other factors : a population-based study of middle-aged Australian-born women?
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