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.

Context: For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and their clinical course during life. Candidate approaches implied that DNA methylation might have a developmental role in CHD and contributes to the long-term progress of non-structural cardiac diseases. The aim of the present study is to define the postnatal epigenome of two common cardiac malformations, representing epigenetic memory, and adaption to hemodynamic alterations, which are jointly relevant for the disease course.', 'We present the first analysis of genome-wide DNA methylation data obtained from myocardial biopsies of Tetralogy of Fallot (TOF) and ventricular septal defect patients. We defined stringent sets of differentially methylated regions between patients and controls, which are significantly enriched for genomic features like promoters, exons, and cardiac enhancers. For TOF, we linked DNA methylation with genome-wide expression data and found a significant overlap for hypermethylated promoters and down-regulated genes, and vice versa. We validated and replicated the methylation of selected CpGs and performed functional assays. We identified a hypermethylated novel developmental CpG island in the promoter of SCO2 and demonstrate its functional impact. Moreover, we discovered methylation changes co-localized with novel, differential splicing events among sarcomeric genes as well as transcription factor binding sites. Finally, we demonstrated the interaction of differentially methylated and expressed genes in TOF with mutated CHD genes in a molecular network.\Question: Does comparative DNA methylation and gene expression analysis identify novel genes for structural congenital heart diseases?
By interrogating DNA methylation and gene expression data, we identify two novel mechanism contributing to the phenotypic expression of CHDs: aberrant methylation of promoter CpG islands and methylation alterations leading to differential splicing.

Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\u2009<\u20090.05 and FC\u2009≥\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\u2009=\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.\Question: Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?
For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.

Context: Despite efficacious treatment, alcohol use disorders contribute significantly to the disability burden. Although wider dissemination of evidence-based health care may impact on the population burden, the affordability of this strategy is unknown. This article compares the cost-effectiveness of current treatment for alcohol use disorders with the cost-effectiveness of optimal treatment, a hypothetical treatment scenario that has been informed by evidence-based practice to determine the affordability of such an approach.', 'This study calculated the cost-effectiveness in the Australian population of evidence-based health care for alcohol harmful use and alcohol dependence, as defined by the International Classification of Diseases, Injuries, and Causes of Death, 10th Revision. Outcome was calculated as years lived with disability (YLD) averted. Data from the Australian National Survey of Mental Health and Wellbeing, in conjunction with published meta-analyses and expert reviews, were used to estimate 1-year costs (1997-98 Australian dollars) and YLD averted by current health care services as well as costs and outcomes for an optimal strategy of evidence-based health care.', 'Of those currently seeking treatment, approximately 45% of those with alcohol harmful use and 58% of those with alcohol dependence receive an evidence-based intervention. The cost of this care was estimated at 73 million dollars, resulting in a cost per YLD averted of 96,813 dollars for harmful use of alcohol and 98,095 dollars for alcohol dependence. Under optimal care for harmful use, costs declined and health gains doubled, substantially reducing the cost per YLD averted to 8861 dollars. For dependence, costs doubled, but optimal treatment resulted in increased health gains, reducing the cost per YLD to 57,542 dollars.\Question: Is evidence-based care for alcohol use disorders affordable?

Evidence-based care for alcohol use disorders would produce greater population health gain at an increased cost for alcohol dependence but at a reduced cost for harmful use of alcohol. For both disorders, there are substantial increases in cost-effectiveness.

