Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Ex Input:
To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development. In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis. In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87). The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.

Ex Output:
Which is the most common gene signature in Rheumatoid Arthritis patients?


Ex Input:
Something strange was unbelievable. Take Robert for example. After the terrible car accident, his whole world had been completely dark and quiet for almost ten years. The loss of sight and hearing made him try many times to put end to his life. His family especially his wife did their best to tend and comfort him. By and by he finally regained the courage to live on. On a hot summer afternoon he was taking a walk with a stick near his house when a thunderstorm started suddenly. He stood under a large tree in order not to get himself wet. Unfortunately he was struck down to the ground by a lightning. The witnesses thought him dead but he woke up some 20 minutes later lying face down in muddy water below the tree. He felt that he was trembling badly, but when he opened his eyes ,he didn't dare to believe that he saw a plough( )lying near the wall. When Mrs Edwards came running up to him, she shouted their neighbours for help. And he saw her and heard her voice for the first time in nearly ten years. The news of Robert's regaining his sight and hearing quickly spread in his area. And many doctors came to prove the truth of the news. Most of them said that he gained sight and hearing again obviously from the knock of lightning; none of them could give convincing reasons, however. The only reasonable explanation given by one doctor was that, since Edwards lost his sight and hearing as a result of sudden shock in a terrible accident, perhaps the only way for them to regain was by another sudden shock.

Ex Output:
What did Edwards see first after being struck down by a lightning?


Ex Input:
Aggregation of -synuclein (Syn), the primary protein component in Lewy body inclusions of patients with Parkinson's disease, arises when the normally soluble intrinsically disordered protein converts to amyloid fibrils. In this work, we provide a mechanistic view of the role of N-terminal acetylation on fibrillation by first establishing a quantitative relationship between monomer secondary structural propensity and fibril assembly kinetics, and secondly by demonstrating in the N-terminal acetylated form of the early onset A53T mutation, that N-terminal transient helices formed and/or inhibited by N-terminal acetylation modulate the fibril assembly rates. Using NMR chemical shifts and fluorescence experiments, we report that secondary structural propensity in residues 5-8, 14-31, and 50-57 are highly correlated to fibril growth rate. A four-way comparison of secondary structure propensity and fibril growth rates of N-terminally acetylated A53T and WT Syn with non-acetylated A53T and WT Syn present novel mechanistic insight into the role of N-terminal acetylation in amyloid fibril formation. We show that N-terminal acetylation inhibits the formation of the "fibrillation promoting" transient helix at residues 14-31 resulting from the A53T mutation in the non-acetylated variant and supports the formation of the "fibrillation inhibiting" transient helix in residues 1-12 thereby resulting in slower fibrillation rates relative to the previously studied non-acetylated A53T variant. Our results highlight the critical interplay of the region-specific transient secondary structure of the N-terminal region with fibrillation, and the inhibitory role of the N-terminal acetyl group in fibril formation.

Ex Output:

Which is the primary protein component of Lewy bodies?