Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Sei-1 is an oncogene capable of inducing double minute chromosomes (DMs) formation. DMs are hallmarks of amplification and contribute to oncogenesis. However, the mechanism of Sei-1 inducing DMs formation remains unelucidated.', 'DMs formation significantly increased during serial passage in vivo and gradually decreased following culture in vitro. micro nuclei (MN) was found to be responsible for the reduction. Of the DMs-carrying genes, Met was found to be markedly amplified, overexpressed and highly correlated with DMs formation. Inhibition of Met signaling decreased the number of DMs and reduced the amplification of the DMs-carrying genes. We identified a 3.57Mb DMs representing the majority population, which consists of the 1.21 Mb AMP1 from locus 6qA2 and the 2.36 Mb AMP2 from locus 6qA2-3.', 'We employed NIH-3T3 cell line with Sei-1 overexpression to monitor and characterize DMs in vivo and in vitro. Array comparative genome hybridization (aCGH) and fluorescence in situ hybridization (FISH) were performed to reveal amplification regions and DMs-carrying genes. Metaphase spread was prepared to count the DMs. Western blot and Met inhibition rescue experiments were performed to examine for involvement of altered Met signaling in Sei-1 induced DMs. Genomic walking and PCR were adopted to reveal DMs structure.
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Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.', 'Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).', 'When genes with an incidence>10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P=.0004) and OS (P.0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.
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The objective of the study was to evaluate work disability and its main associated factors in patients with early arthritis. Argentine Consortium for Early Arthritis (CONAART) is the first early arthritis cohort in Argentina. Patients with one or more swollen joints and less than 2 years of symptoms duration were followed up prospectively in 13 departments of rheumatology. Social, demographic, familiar, clinical, and laboratory data were recollected. At first year and every year, X-rays of hands and feet were performed and working status and pharmaco-economic data were recollected. Work status (employed, unemployed, retired) and type of work were assessed by direct interview using a predesigned questionnaire. Eight hundred forty-eight patients were included, rheumatoid arthritis (RA)=483 (57 %)and undifferentiated arthritis (UA)=365 (43 %), 694 (81.8 %) were women, median age was 46 years (interquartile range (IQR) 35-55.7) and median symptoms duration 7 months (IQR 3-12). Patients with RA had significantly higher disease activity, worse functional capacity and quality of life, and more severe radiological damage compared to UA patients. However work disability (unemployed patient) was comparable between groups (RA=21 % versus UA=18.6 % p=NS). In both groups, unemployed patients had higher disease activity score of 28 joints (DAS28), worse Health Assessment Questionnaire (HAQ) values, and less years of formal education (p value <0.005 in all comparisons). Radiological damage was greater in unemployed patients but this difference did not reach statistical significance. In multivariate analysis, disease activity was the main variable associated with unemployment in both groups. Joint involvement was the main cause of work disability in this cohort of patients with early arthritis, independently of the final diagnosis.
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