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 Q]: Context: Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients.', 'Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period.', 'Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors.
Answer: The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.
[EX A]: Is reactive hyperemia associated with adverse clinical outcomes in heart failure?

[EX Q]: Context: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.', 'Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.
Answer: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.
[EX A]: Does dll1 haploinsufficiency in adult mice lead to a complex phenotype affecting metabolic and immunological processes?

[EX Q]: Context: Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive.
Answer: Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of platelet-expressed FVIII than are required for therapeutic efficacy in hemophilia A are not associated with a thrombotic predilection.
[EX A]:
Does targeting factor VIII expression to platelets for hemophilia A gene therapy induce an apparent thrombotic risk in mice?