TASK DEFINITION: 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.
PROBLEM: Context: We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures.', 'Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF.', "Mean age was 50.0±15.0\u2005years; 322 (68%) were men. At a median of 4.3\u2005years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end-systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035).
Answer: In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.

SOLUTION: Is global longitudinal strain associated with heart failure outcomes in hypertrophic cardiomyopathy?

PROBLEM: Context: Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by a mutation in DMD encoding dystrophin. Oxidative stress accounts for dystrophic muscle pathologies in DMD. We examined the effects of molecular hydrogen in mdx mice, a model animal for DMD.', 'The pregnant mother started to take supersaturated hydrogen water (>5\u2005ppm) ad libitum from E15.5 up to weaning of the offspring. The mdx mice took supersaturated hydrogen water from weaning until age 10 or 24 weeks when they were sacrificed.', 'Hydrogen water prevented abnormal body mass gain that is commonly observed in mdx mice. Hydrogen improved the spontaneous running distance that was estimated by a counter-equipped running-wheel, and extended the duration on the rota-rod. Plasma creatine kinase activities were decreased by hydrogen at ages 10 and 24 weeks. Hydrogen also decreased the number of central nuclei of muscle fibers at ages 10 and 24 weeks, and immunostaining for nitrotyrosine in gastrocnemius muscle at age 24 weeks. Additionally, hydrogen tended to increase protein expressions of antioxidant glutathione peroxidase 1, as well as anti-apoptotic Bcl-2, in skeletal muscle at age 10 weeks.
Answer: Although molecular mechanisms of the diverse effects of hydrogen remain to be elucidated, hydrogen potentially improves muscular dystrophy in DMD patients.

SOLUTION: Does molecular hydrogen alleviate motor deficits and muscle degeneration in mdx mice?

PROBLEM: Context: Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.', 'By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the alpha3 domain, but our results suggest that homogenisation also concerns certain residues of the alpha1-alpha2 codomain that lie outside the antigen recognition site.
Answer: A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation.

SOLUTION:
Is the orthology of HLA-E and H2-Qa1 hidden by their concerted evolution with other MHC class I molecules?