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.

del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.
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Imitation, which is impaired in children with autism spectrum disorder (ASD) and critically depends on the integration of visual input with motor output, likely impacts both motor and social skill acquisition in children with ASD; however, it is unclear what brain mechanisms contribute to this impairment. Children with ASD also exhibit what appears to be an ASD-specific bias against using visual feedback during motor learning. Does the temporal congruity of intrinsic activity, or functional connectivity, between motor and visual brain regions contribute to ASD-associated deficits in imitation, motor, and social skills?', 'We acquired resting-state functional magnetic resonance imaging scans from 100 8- to 12-year-old children (50 ASD). Group independent component analysis was used to estimate functional connectivity between visual and motor systems. Brain-behavior relationships were assessed by regressing functional connectivity measures with social deficit severity, imitation, and gesture performance scores.', 'We observed increased intrinsic asynchrony between visual and motor systems in children with ASD and replicated this finding in an independent sample from the Autism Brain Imaging Data Exchange. Moreover, children with more out-of-sync intrinsic visual-motor activity displayed more severe autistic traits, while children with greater intrinsic visual-motor synchrony were better imitators.
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Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis.', 'We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis.', 'Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).

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