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.

Input: Consider 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.\Question: Are dNA methylation subgroups in melanoma associated with proliferative and immunological processes?

Output: Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.


Input: Consider Input: Context: Our previous work demonstrated altered messenger RNA expression of integrin β-5 and -8, using an in silico analysis of publically available data from patients with biliary atresia (BA); however, we were unable to demonstrate statistically significant differences in protein expression because of sample size. In the present study, we repeated the analysis of liver fibrosis and protein expression of the integrins in a larger cohort of patients with BA and compared them with patients undergoing liver biopsy for other diagnoses, with the hypothesis that ≥ 1 of the integrins would be differentially expressed.', 'Liver specimens were obtained at 2 collaborating institutions. Samples from infants with BA (n = 23) were compared with samples from those who underwent liver biopsy for neonatal hepatitis (n = 9). All of the specimens were analyzed by 2 pathologists (C.R. and R.A.), who were blinded to the diagnoses. Standard Ishak scoring was performed to evaluate fibrosis and inflammation, and immunohistochemical (IHC) positivity was graded from 0 to 4. Comparisons between the IHC positivity and Ishak scoring for the BA and control groups were performed using the Student t test with P < 0.01 considered significant because of the multiple comparisons. Interobserver variability was assessed by intraclass correlation (ICC).', 'Pooled analysis from specimens from patients with BA showed significantly more fibrosis than controls based on Ishak scores (3.21 ± 1.82 vs 1.17 ± 1.00, P < 0.005). IHC evaluation showed increased integrin ανβ8 protein expression when compared with controls (2.67 ± 0.81 vs 1.72 ± 0.62, P < 0.005); however, there were no significant differences in integrin ανβ5 (1.93 ± 0.84 vs 1.50 ± 0.90, P = 0.23) or integrin ανβ6 (0.85 ± 1.20 vs 0.94 ± 0.85, P = 0.82) expression. These data were confirmed on individual analysis. Interobserver agreement was fair for integrin ανβ5 (ICC 0.52), good for integrin ανβ6 (ICC 0.72), and excellent for integrin ανβ8 (ICC 0.79) and fibrosis (ICC 0.89).\Question: Is integrin β-8 , but not β-5 or -6 , protein expression increased in livers of children with biliary atresia?

Output: Our data show that integrin ανβ8, but not integrin ανβ5 or integrin ανβ6, protein expression is increased in liver specimens of patients with BA. These data support the mounting evidence that transforming growth factor-β (TGF-β) activation is responsible for the fibrosis found in BA. Anti-integrin ανβ8 or more global integrin blocking strategies may be therapeutic options in BA, but further work is clearly needed.


Input: Consider Input: Context: Chronic opioid therapy for chronic pain treatment has increased. Hospital physicians, including hospitalists and medical/surgical resident physicians, care for many hospitalized patients, yet little is known about opioid prescribing at hospital discharge and future chronic opioid use.', "We aimed to characterize opioid prescribing at hospital discharge among 'opioid naïve' patients. Opioid naïve patients had not filled an opioid prescription at an affiliated pharmacy 1 year preceding their hospital discharge. We also set out to quantify the risk of chronic opioid use and opioid refills 1 year post discharge among opioid naïve patients with and without opioid receipt at discharge.", 'This was a retrospective cohort study.', 'From 1 January 2011 to 31 December 2011, 6,689 opioid naïve patients were discharged from a safety-net hospital.', 'Chronic opioid use 1 year post discharge.', 'Twenty-five percent of opioid naïve patients (n\u2009=\u20091,688) had opioid receipt within 72 hours of discharge. Patients with opioid receipt were more likely to have diagnoses including neoplasm (6.3% versus 3.5%, p\u2009<\u20090.001), acute pain (2.7% versus 1.0 %, p\u2009<\u20090.001), chronic pain at admission (12.1% versus 3.3%, p\u2009<\u20090.001) or surgery during their hospitalization (65.1% versus 18.4%, p\u2009<\u20090.001) compared to patients without opioid receipt. Patients with opioid receipt were less likely to have alcohol use disorders (15.7% versus 20.7%, p\u2009<\u20090.001) and mental health disorders (23.9% versus 31.4%, p\u2009<\u20090.001) compared to patients without opioid receipt. Chronic opioid use 1 year post discharge was more common among patients with opioid receipt (4.1% versus 1.3%, p\u2009<\u20090.0001) compared to patients without opioid receipt. Opioid receipt was associated with increased odds of chronic opioid use (AOR\u2009=\u20094.90, 95% CI 3.22-7.45) and greater subsequent opioid refills (AOR\u2009=\u20092.67, 95% CI 2.29-3.13) 1 year post discharge compared to no opioid receipt.\Question: Does opioid Prescribing at Hospital Discharge contribute to Chronic Opioid Use?


Output: Opioid receipt at hospital discharge among opioid naïve patients increased future chronic opioid use. Physicians should inform patients of this risk prior to prescribing opioids at discharge.