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: Pineal function has been considered particularly as a neuroendocrine modulator in hormone responsive tumors, like the hormone-dependent mammary tumors. The complexity of the gland function, moreover, is denoted by the presence of a local renin-angiotensin-system (RAS) that regulates melatonin biosynthesis. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. Our aim is to know their role in the regulation of pineal RAS and breast cancer.', 'Aminopeptidase N (APN), aminopeptidase B (APB) and aminopeptidase A (aspartyl- and glutamyl-aminopeptidase, APA) activities are measured in the pineal gland of rats with breast cancer induced by N-methyl nitrosourea (NMU).', 'Aminopeptidase activities were measured fluorimetrically using their corresponding aminoacyl-beta-naphthylamides as substrates.', 'Specific APN and APB activities in pineal gland of controls and NMU-treated rats were not modified. Aspartyl aminopeptidase activity significantly decreased in NMU-treated rats when compared with control group. On the contrary, glutamyl aminopeptidase activity did not show significant differences between groups.
Answer: We propose that the local RAS in pineal gland is modified in rats with breast cancer induced by NMU through the inhibition of AspAP activity, which may lead to increased levels of Ang II. Ang II could be responsible of the overproduction of melatonin, supporting a mechanism to restrain the promotion and/or progression of breast cancer.
[A]: Are renin-angiotensin system-regulating aminopeptidase activities modified in the pineal gland of rats with breast cancer induced by N-methyl-nitrosourea?

[Q]: Context: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', "We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with 1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.", 'Of 113677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged 50years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.
Answer: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
[A]: Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?

[Q]: Context: Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.', 'Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n=11), placebo (n=13) or PEG-IFNa-2a alone (n=6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.', 'Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.
Answer: PEG-IFNa activates NK cells possibly contributing to virological responses independently of RBV. The role of NK cells during future IFN-free combination therapies including RBV remains to be determined.
[A]:
Does pEG-IFN alpha but not ribavirin alter NK cell phenotype and function in patients with chronic hepatitis C?