In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

[Q]: Context: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets.', 'Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n\u2009=\u2009174).', 'Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p\u2009=\u20090.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p\u2009=\u20090.0019) as well as with cathepsin B and D (p\u2009≤\u20090.0001) that are implicated in cell invasion and metastasis.\Question: Does uPAR enhance malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R?
[A]: Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC.


[Q]: Context: The present study aimed to identify the relationship between glycemic variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients with good glycemic control.', 'Two-hundred forty consecutive T2DM patients (HbA1c≤7.0%) without CVD were included to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3 groups: low-risk group (FRS≤10%), intermediate-risk group (>10%, ≤20%) and high-risk group (>20%). Inter-group differences of GV were determined by comparing the SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring system.', 'The levels of SDBG and MAGE significantly increased along with the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525, 0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793), p<0.001] were independent predictors for high 10-y CVD risk.\Question: Is glycemic variability evaluated by continuous glucose monitoring system associated with the 10-y cardiovascular risk of diabetic patients with well-controlled HbA1c?
[A]: GV predicts independently the 10-y CVD risk of T2DM patients with well-controlled HbA1c.


[Q]: Context: Notch signaling plays an acknowledged role in bile-duct development, but its involvement in cholangiocyte-fate determination remains incompletely understood. We investigated the effects of early Notch2 deletion in Notch2(fl/fl)/Alfp-Cre(tg/-) ("Notch2-cKO") and Notch2(fl/fl)/Alfp-Cre(-/-) ("control") mice. Fetal and neonatal Notch2-cKO livers were devoid of cytokeratin19 (CK19)-, Dolichos-biflorus agglutinin (DBA)-, and SOX9-positive ductal structures, demonstrating absence of prenatal cholangiocyte differentiation. Despite extensive cholestatic hepatocyte necrosis and growth retardation, mortality was only ~15%. Unexpectedly, a slow process of secondary cholangiocyte differentiation and bile-duct formation was initiated around weaning that histologically resembled the ductular reaction. Newly formed ducts varied from rare and non-connected, to multiple, disorganized tubular structures that connected to the extrahepatic bile ducts. Jaundice had disappeared in ~30% of Notch2-cKO mice by 6 months. The absence of NOTCH2 protein in postnatally differentiating cholangiocyte nuclei of Notch2-cKO mice showed that these cells had not originated from non-recombined precursor cells. Notch2 and Hnf6 mRNA levels were permanently decreased in Notch2-cKO livers. Perinatally, Foxa1, Foxa2, Hhex, Hnf1β, Cebpα and Sox9 mRNA levels were all significantly lower in Notch2-cKO than control mice, but all except Foxa2 returned to normal or increased levels after weaning, coincident with the observed secondary bile-duct formation. Interestingly, Hhex and Sox9 mRNA levels remained elevated in icteric 6 months old Notch2-cKOs, but decreased to control levels in non-icteric Notch2-cKOs, implying a key role in secondary bile-duct formation.\Question: Does hepatic Notch2 deficiency lead to bile duct agenesis perinatally and secondary bile duct formation after weaning?
[A]:
Cholangiocyte differentiation becomes progressively less dependent on NOTCH2 signaling with age, suggesting that ductal-plate formation is dependent on NOTCH2, but subsequent cholangiocyte differentiation is not.