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.

Input: Consider Input: Context: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.", "In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >\u2009C polymorphism in exon 98 and c.14693 T >\u2009C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.
Answer: Considering that patient's relatives showed no pathologic phenotype, and the phenotype presented by the patient is within the range observed in other central core disease patients with the same mutation, it was concluded that the c.14256 A > C polymorphism alone is not responsible for disease, and the associated additional silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The case described above illustrates the present reality where new methods for wide genome screening are becoming more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in patients and their families.

Output: Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?


Input: Consider Input: Context: Ischemic mitral regurgitation (MR) often persists after restrictive mitral valve annuloplasty, in which case it is associated with worse clinical outcomes. The goal of the present study was to determine whether persistence of MR and/or clinical outcome could be predicted from preoperative analysis of mitral valve configuration.', 'In 51 consecutive patients undergoing restrictive annuloplasty for ischemic MR, posterior leaflet (PL) angle, anterior leaflet angle, coaptation distance, and tenting area were quantified by echocardiography before surgery (6+/-3 days), and MR severity was assessed before and early after surgery (9+/-4 days). Postoperatively, persistence of mild to moderate MR (vena contracta > 3 mm) was observed in 11 (22%) of the patients. The best predictor of postoperative persistence of MR was a PL angle > or = 45 degrees (sensitivity 100%, specificity 97%, positive predictive value 92%, negative predictive value 100%). Patients with persistent MR had markedly lower 3-year event-free survival (26+/-20%) compared with those with nonpersistent MR (75+/-12%, P=0.01). Preoperative presence of a PL angle > or = 45 degrees also was associated with a markedly lower 3-year event-free survival (22+/-17% versus 76+/-12%; P<0.001).
Answer: In patients undergoing restrictive annuloplasty for ischemic MR, persistence of MR and 3-year event-free survival can accurately be predicted by preoperative analysis of mitral valve configuration. Patients with a PL angle > or = 45 degrees (ie, with high PL restriction) should thus be considered poor candidates for this procedure, and concomitant or alternative procedures should be contemplated.

Output: Does preoperative posterior leaflet angle accurately predict outcome after restrictive mitral valve annuloplasty for ischemic mitral regurgitation?


Input: Consider Input: Context: The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC).', 'The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control.', 'Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059).
Answer: Our study indicates that the expression of cyclin D1 correlates with the presence of occult cervical metastases in head and neck carcinoma patients, thus suggesting that its immunohistochemical evaluation in biopsy samples may be used as an additional tool for identifying patients to be treated with elective neck dissection.


Output: Is cyclin D1 expression predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes?