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.

[Q]: Human hepatocellular carcinoma (HCC) heterogeneity promotes recurrence and resistance to therapies. Recent studies have reported that HCC may be derived not only from adult hepatocytes and hepatoblasts but also hepatic stem/progenitors. In this context, HepaRG cells may represent a suitable cellular model to study stem/progenitor cancer cells and the retrodifferentiation of tumor-derived hepatocyte-like cells. Indeed, they differentiate into hepatocyte- and biliary-like cells. Moreover, tumor-derived HepaRG hepatocyte-like cells (HepaRG-tdHep) differentiate into both hepatocyte- and biliary-like cells through a hepatic progenitor. In this study we report the mechanisms and molecular effectors involved in the retrodifferentiation of HepaRG-tdHep into bipotent progenitors. Gene expression profiling was used to identify genomic changes during the retrodifferentiation of HepaRG-tdHep into progenitors. We demonstrated that gene expression signatures related to a poor-prognosis HCC subclass, proliferative progenitors, or embryonic stem cells were significantly enriched in HepaRG progenitors derived from HepaRG-tdHep. HepaRG-tdHep retrodifferentiation is mediated by crosstalk between transforming growth factor beta 1 (TGFβ1) and inflammatory cytokine pathways (e.g., tumor necrosis factor alpha [TNFα] and interleukin 6 [IL6]). Signatures related to TNFα, IL6, and TGFβ activation pathways are induced within the first hour of retrodifferentiation. Moreover, specific activation or inhibition of these signaling pathways allowed us to determine that TNFα and IL6 contribute to the loss of hepatic-specific marker expression and that TGFβ1 induces an epithelial-to-mesenchymal transition of HepaRG-tdHep. Interestingly, the retrodifferentiation process is blocked by the histone deacetylase inhibitor trichostatin A, opening new therapeutic opportunities.
[A]: 0


[Q]: To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC).', 'RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells.', 'Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 microM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001).
[A]: 0


[Q]: It has been reported previously that the paired interpretation of the corticotrophin-releasing hormone (CRH) test and the 8-mg dexamethasone suppression test (HDDST) could have higher diagnostic power than any single test in the differential diagnosis of ACTH-dependent Cushing's syndrome. This finding has not been confirmed thereafter in large series. The aim of the present study has been to assess the operating characteristics of either the CRH test or the overnight HDDST and also to evaluate the potential utility of combining the interpretation of both tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.", "We have reviewed the medical records of 59 consecutive cases with ACTH-dependent Cushing's syndrome: 49 patients with proven Cushing's disease (CD) and 10 patients with proven ectopic ACTH syndrome (EAS). Univariate curves of the receiver operating characteristics (ROC) have been performed to define the best cut-off values, the sensitivity and the specificity for CRH and overnight HDDST. A comparison between the areas under the ROC curves has also been performed.", 'For the CRH test, the point on the ROC curve closest to 1 corresponded to a value of ACTH percentage increment of 50%[sensitivity 86% (72.6-94.8) and specificity 90% (55.5-98.3)]. The best threshold for cortisol percentage (30%) increment gave inferior results [sensitivity 61% (45.5-75.6) and specificity 70% (34.8-93.0)]. For the HDDST, the point on the ROC curve closest to 1 corresponded to a value of cortisol decrease from the baseline of 50%[sensitivity 77% (62.7-88.5), specificity 60% (26.4-87.6)]. The area under the ROC curve of the ACTH percentage increment after CRH was significantly greater than the area under the diagonal [0.9 (0.7-1.0), P= 0.0001]. Conversely, the area under the cortisol percentage decrement after dexamethasone was not different from that obtained by chance [0.7 (0.5-0.9), P= ns]. The area under the ROC curve of CRH is significantly greater than that of overnight HDDST (P = 0.03). A correct diagnosis has been achieved by the CRH test in 86.5% of cases and by the HDDST in 73% (P = 0.06). The combination of both tests has given a correct diagnosis in a significantly lower percentage of cases than the CRH test alone (69%, P= 0.04). The bilateral inferior petrosal sinus sampling (BIPSS) has been performed in 29 patients (24 CD, five EAS) who had negative imaging and/or discordant results of the noninvasive tests. Considering the criterion of a central to peripheral ACTH ratio > 3 after CRH stimulation, a correct diagnosis was achieved in all cases.
[A]:
1