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
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Q: In patients undergoing total knee replacement (TKR), most blood loss occurs post-operatively, and the return of unwashed filtered shed blood (USB) from post-operative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return on the cellular immune response (CIR) after TKR.', 'Forty TKR patients, intended to receive post-operative USB, entered the study. Blood samples were obtained before and 6 h, 24 h, 72 h and 7 days after surgery, and from USB, after it had been passed through a 40-microm filter. Full blood cell counts, lymphocyte subsets and immunoglobulins (IgA, IgG, IgM) were measured in all samples. A set of clinical data was collected from each patient.', 'Twenty-four of the 25 patients received a mean of 1.2 USB units and did not need additional ABT (USB group). Twelve of the 15 remaining patients who received neither USB nor ABT served as a control group for the post-operative CIR study. All patients showed a post-operative decrease in T-cell and natural killer (NK) cell counts, but not B-cell counts, and there were no significant differences between the groups with regard to CIR parameters, post-operative infection or hospital stay.

A: 0
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Q: Brivaracetam (BRV) is an antiepileptic drug in Phase III clinical development. BRV binds to synaptic vesicle 2A (SV2A) protein and is also suggested to inhibit voltage-gated sodium channels (VGSCs). To evaluate whether the effect of BRV on VGSCs represents a relevant mechanism participating in its antiepileptic properties, we explored the pharmacology of BRV on VGSCs in different cell systems and tested its efficacy at reducing the sustained repetitive firing (SRF).', 'Brivaracetam investigations on the voltage-gated sodium current (I(Na)) were performed in N1E-155 neuroblastoma cells, cultured rat cortical neurons, and adult mouse CA1 neurons. SRF was measured in cultured cortical neurons and in CA1 neurons. All BRV (100-300 μM) experiments were performed in comparison with 100 μM carbamazepine (CBZ).', 'Brivaracetam and CBZ reduced IN a in N1E-115 cells (30% and 40%, respectively) and primary cortical neurons (21% and 47%, respectively) by modulating the fast-inactivated state of VGSCs. BRV, in contrast to CBZ, did not affect I(Na) in CA1 neurons and SRF in cortical and CA1 neurons. CBZ consistently inhibited neuronal SRF by 75-93%.

A:
1
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