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.

Ex Input:
Context: Alterations in epigenetic processes are frequently noted in human disease. These epigenetic processes involve methylation of DNA and post-translational modifications of histones. It is well established that in particular histone methylation plays a key role in gene transcription. In this study, we have investigated the relationship between triple methylation of lysine 27 in histone H3 (H3K27Me3) modifications and atherosclerotic plaque stage.', '28 peri-renal aortic tissue patches covering the entire spectrum of atherosclerotic plaque development were evaluated by immunohistochemistry for the levels of H3K27Me3, EZH2, JMJD3 and BMI1.', 'The results of our studies are in support of a reduction in global levels of the H3K27Me3 modification in vessels with advanced atherosclerotic plaques. This reduction in H3K27Me3 levels is not accompanied by alterations in global levels of the corresponding histone methyltransferase EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Likewise no alterations in global levels of BMI1, a component of the PRC1 complex, which binds to H3K27Me3-modified histones or the global expression levels of the histone demethylase JMJD3, which removes the methyl marks on H3K27, were observed.
Answer: Together, our data show that in atherosclerosis development alterations in global levels of H3K27Me3 occur. The reduction in the number of nuclei in the tunica media that display the repressive H3K27Me3 mark in vessels with advanced atherosclerosis plaques therefore could be a reflection of the dynamic pattern of smooth muscle cell differentiation and proliferation associated with atherosclerotic disease.

Ex Output:
Are global histone H3 lysine 27 triple methylation levels reduced in vessels with advanced atherosclerotic plaques?


Ex Input:
Context: Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND).', 'In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison.', 'A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p\xa0= 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p\xa0=\xa00.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p\xa0= 0.9044).
Answer: Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.

Ex Output:
Does molecular Staging of Sentinel Lymph Nodes identify Melanoma Patients at Increased Risk of Nodal Recurrence?


Ex Input:
Context: Within Australian hospitals, cardiac and respiratory arrests result in a resuscitation attempt unless the patient is documented as not for resuscitation.', 'To examine the consistency of policies and documentation for withholding in-hospital resuscitation across health services.', 'An observational, qualitative review of hospital policy and documentation was conducted in June 2013 in three public and two private sector hospitals in metropolitan Melbourne. Not for resuscitation (NFR) forms were evaluated for physical characteristics, content, authorisation and decision-making. Hospital policies were coded for alerts, definition of futility and burden of treatment and management of discussions and dissent.', 'There was a lack of standardisation, with each site using its own unique NFR form and accompanying site-specific policies. Differences were found in who could authorise the decision, what was included on the form, the role of patients and families, and how discussions were managed and dissent resolved. Futility and burden of treatment were not defined independently. These inconsistencies across sites contribute to a lack of clarity regarding the decision to withhold resuscitation, and have implications for staff employed across multiple hospitals.
Answer: NFR forms should be reviewed and standardised so as to be clear, uniform and consistent with the legislative framework. We propose a two-stage process of documentation. Stage 1 facilitates discussion of patient-specific goals of care and consideration of limitations of treatment. Stage 2 serves to communicate a NFR order. Decisions to withhold resuscitation are inherently complex but could be aided by separating the decision-making process from the communication of the decision, resulting in improved end-of-life care.

Ex Output:

Does comparison of not for resuscitation ( NFR ) form across five Victorian health services?