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.

Input: Consider Input: 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.

Output: 0


Input: Consider Input: The canals of Hering (CoH), which are the most peripherally located bile drainage pathway, are considered a niche of hepatic progenitor cells. Recently, CoH loss has been described as an early feature of primary biliary cirrhosis (PBC). We investigated the correlation between CoH loss and the histopathological variables of PBC.', 'Liver biopsy specimens from 62 PBC patients (M:F=8:54, age=58 ± 12 years) were evaluated prior to ursodeoxycholic acid treatment. Liver biopsies of patients with normal liver (n=11), chronic viral hepatitis (n=36) and non-alcoholic fatty liver disease (n=13) were used as controls. The number of CoH per definite area of hepatic parenchyma (c to p ratio) was calculated in individual cases. We compared the c to p ratios of PBC patients with that of controls and analysed the correlations with histological variables and clinical features.', 'The c to p ratios in PBC patients with mild and extensive fibrosis were lower than those in controls with each degree of fibrosis. The c to p ratios were negatively correlated with stage, fibrosis, bile duct loss, orcein-positive granule deposition and hepatitis activities in PBC (p<0.01) and with alkaline phosphatase and total bilirubin levels at liver biopsies (p<0.05).

Output: 1


Input: Consider Input: To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa.', 'In 316 patients with typical forms of retinitis pigmentosa, visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were detected with optical coherence tomography (OCT), and retinal thicknesses was quantified by OCT. The FREQ, LOGISTIC, and GENMOD procedures of SAS (SAS Institute, Cary, NC) were used to evaluate possible risk factors for cyst prevalence, and the MIXED procedure was used to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula.', 'Macular cysts were found in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (P = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (P = 0.038) and within a parafoveal ring spanning an eccentricity of 5 degrees to 10 degrees from the foveal center (P = 0.004).


Output: 1