instruction:
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.
question:
Context: The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice.', 'Individual hybridomas isolated from the spleen of a 10-month-old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme-linked immunosorbent assay, Western blotting, 2-dimensional gel electrophoresis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high-throughput epitope mapping method.', 'The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)-modified enolase, Ro, alpha-actin, and heat-shock proteins (HSPs) preceding peak levels of antihistone, anti-DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT-modified enolase, ATP5b, alpha-actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism.
Answer: The polyreactivity of autoantibodies that target a novel class of autoantigens may enable these autoantibodies to induce erosive arthritis or glomerulonephritis either by direct pathogenic mechanisms or indirectly via Fc or immune complex deposition.
answer:
Does production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice cause glomerulonephritis and arthritis?


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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.
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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?


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Context: We investigated the relationship between preoperative psychological state and postoperative confusion in elderly drinkers.', 'We studied 81 male patients, ranging in age from 65 to 80 years, who were scheduled to undergo total hip arthroplasty and total knee arthroplasty. The patients were divided into two groups; non-drinkers and patients who drank 25 g or more of alcohol daily. All patients were given a neuropsychological screening evaluation, including a Mini-Mental State test, the Japanese version of the State-Trait Anxiety Inventory (STAI), a depression scale test, and evaluation of a history of aggression and postoperative confusion.', 'Postoperative confusion during the first 72 h after the end of the operation occurred in 7 of the 50 non-drinkers (14%) and in 11 of the 31 drinkers (35%) (P = 0.01). There were no significant differences in STAI (state anxiety and trait anxiety), Mini-Mental State, and depression scale scores between the non-drinkers and drinkers, or between patients with and without postoperative confusion. All 8 patients who had a history of aggression developed postoperative confusion. There was no significant difference in the incidence of postoperative confusion between drinkers who did not have a history of aggression and non-drinkers.
Answer: A history of aggression in elderly male drinkers is associated with postoperative confusion.
answer:

Is a history of aggression a risk factor for postoperative confusion in elderly male drinkers?