TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms.', 'Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing.', 'The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors.', 'Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts ( P < .001). Within the isoform-specific regions of the autoantigens, 92% and 88% encoded MHC class I and class II-restricted T-cell antigen epitopes, respectively, and 70% encoded antibody binding domains. Furthermore, 80% of the autoantigen transcripts underwent noncanonical alternative splicing, which is also significantly higher than the less than 1% rate in randomly selected gene transcripts ( P < .001).\Question: Does increased noncanonical splicing of autoantigen transcripts provide the structural basis for expression of untolerized epitopes?

SOLUTION: These studies suggest that noncanonical alternative splicing may be an important mechanism for the generation of untolerized epitopes that may lead to autoimmunity. Furthermore, the product of a transcript that does not undergo alternative splicing is unlikely to be a target antigen in autoimmunity.

PROBLEM: Context: To assess how different imputation methods used to account for missing variance data in primary studies influence tests of heterogeneity and pooled results from a meta-analysis with continuous outcomes.', 'Point and variance estimates for changes in serum creatinine, glomerular filtration rate, systolic blood pressure, and diastolic blood pressure were variably reported among 48 primary longitudinal studies of living kidney donors (71%-78% of point estimates were reported, 8%-13% of variance data were reported). We compared the results of meta-analysis, which either were restricted to available data or used four methods to impute missing variance data. These methods used reported P-values, reported nonparametric summaries, results from other similar studies using multiple imputation, or results from estimated correlation coefficients.', 'Significant heterogeneity was present in all four outcomes regardless of the imputation methods applied. The random effects point estimates and 95% confidence intervals varied little across imputation methods, and the differences were not clinically significant.\Question: Do imputing variance estimates alter the conclusions of a meta-analysis with continuous outcomes : a case study of changes in renal function after living kidney donation?

SOLUTION: Different methods to impute the variance data in the primary studies did not alter the conclusions from this meta-analysis of continuous outcomes. Such reproducibility increases confidence in the results. However, as with most meta-analyses, there was no gold standard of truth, and results must be interpreted judiciously. The generalization of these findings to other meta-analyses, which differ in outcomes, missing data, or between-study heterogeneity, requires further consideration.

PROBLEM: Context: Viral infections are associated with both mild and severe exacerbations of asthma and may therefore be associated with asthma death. As such we hypothesized that it might be possible to detect rhinovirus (RV), the virus most frequently implicated in acute asthma, in lung tissue from patients who died from asthma.', 'We studied archival, wax-embedded lung tissue obtained postmortem from: (i) patients who died from asthma (n = 12), (ii) asthma patients with non-asthma-related death (n = 3), and (iii) non-asthmatic individuals who died from unrelated causes (n = 3). A validated reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect RV. To confirm RNA preservation, RT-PCR was used to detect expression of the constitutive gene adenine-phosphoribosyl-transferase (APRT). Sensitivity of the assay was assessed using wax-embedded RV-infected cells.', 'Sensitivity of RT-PCR for RV in wax-embedded sections was similar to previous studies (approximately 100 viral copies). Specimens used for study were predominantly of alveolar and small airway origin (< 2 mm). All tissues examined were negative for the presence of RV mRNA and positive for APRT mRNA.\Question: Is rhinovirus detectable in peripheral lung tissue after asthma death?

SOLUTION:
RV infection of the lower airway may be an uncommon cause of fatal asthma. Alternatively, RV may not extend to peripheral airways and more proximal tissue sampling or PCR assays for other viruses may be required to determine an association between viral respiratory tract infection and fatal asthma.