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.

Example Input: 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.
Example Output: Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?

Example Input: Context: DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity.', 'We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data.', 'We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes.
Answer: Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.
Example Output: Are dNA methylation subgroups in melanoma associated with proliferative and immunological processes?

Example Input: Context: The cause of rheumatoid arthritis (RA) flares is multifactorial and not well understood. No reports of fractures influencing disease activity in patients with RA have been published. The purpose of this study was to determine whether fractures influence disease activity in patients with RA.', 'Hospital records of 470 patients with RA between 2011 and 2014 were analyzed. We first examined the incidence of flare using multiple regression analysis. Secondly, we examined the incidence of flare using DAS28-ESR, DAS28-CRP, and drug changes before bone fracture until bone union in the fracture cases.', 'Multiple linear regression analysis showed that female sex (p\u2009<\u20090.001), bottom DAS28-ESR (p\u2009<\u20090.001), and fracture (p\u2009=\u20090.041) were independent factor for DAS28-ESR at the last observation period, and sex (p\u2009=\u20090.040), bottom DAS28-CRP (p\u2009<\u20090.001), and fracture (p\u2009=\u20090.019) were independent factor for DAS28-CRP at the last observation period. The average DAS28-ESR value was significantly increased from 3.19 (prefracture) to 3.58 (bone union). The average DAS28-CRP value was also significantly increased from 2.45 (prefracture) to 2.79 (bone union).
Answer: We have demonstrated that fractures influence disease activity in patients with RA. Larger numbers of fracture cases are required to confirm the present observations; however, the prevention of fracture is clearly required in patients with RA.
Example Output:
Do fractures lead to worsening of disease activity in rheumatoid arthritis?