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.

Input: Consider Input: 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?

Output: 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.


Input: Consider Input: Context: The measurement of affective symptoms in older persons who decline cognitively is uncertain. The authors investigated whether mood variability predicts dementia in patients with age-related macular degeneration (AMD).', 'Three-year observational study after a clinical trial.', 'Community follow-up of outpatients ascertained from retina clinics.', 'One hundred sixty patients with AMD.', "Geriatric Depression Scale (GDS) administered every 2 weeks for 6 months to subjects; Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to subjects' knowledgeable informants.", 'Twenty-three subjects (14.4%) declined cognitively. Age, education, baseline GDS score > or =5, and variability in GDS scores (i.e., fluctuations between adjacent time points) were associated with cognitive decline. For GDS variability, each 1 unit increase in the residual standard deviation (SD) of the GDS increased the risk for cognitive decline by 93% (IDR = 1.92; 95% CI [1.27-2.91]). Thus, subjects with a residual SD of 1 were nearly twice as likely to become demented as subjects with no variability in GDS scores. The risk for subjects with SDs of 2 increased more than threefold (IDR = 3.68; 95% CI [1.61-8.47]). A multiple regression analysis showed that GDS variability was a significant risk factor for dementia after controlling for significant covariates.\Question: Does variability in depressive symptoms predict cognitive decline in age-related macular degeneration?

Output: These data suggest a useful approach to conceptualizing and measuring depressive symptoms in older persons. Variability in self-reported mood may be an early sign of dementia and may offer new insights into the neurobiological mechanisms linking depression and cognition


Input: Consider Input: Context: A distinct velocity pattern represented by a "notch" is observed during the time interval between the end of the systolic and the onset of the early diastolic velocity wave on longitudinal myocardial velocity curve. The origin of the post-systolic velocity notch (PSN) has not been resolved.', 'The high frame rate color tissue Doppler imaging of the apical longitudinal axis was performed in 32 healthy subjects.', 'The time delays of the PSN onset at the posterior aortic wall (AW), the mid anteroseptal wall (MAS) and the posterior mitral annulus (MA) relatively to the anterior aortic annulus (AA) were found to be significantly longer than zero (5.1 ± 2.2, 6.0 ± 2.3, 6.8 ± 2.8 ms; p < 0.001). The amplitude was the highest at the AA when compared to the AW, the MAS and the MA (4.77 ± 1.28 vs. 2.88 ± 1.11, 2.15 ± 0.73, 2.44 ± 1.17 cm/s; p < 0.001). A second PSN spike was identifiable in 10/32 (31%) of the studied subjects at the AA. Of these, 9 (28%) exhibited a second PSN spike at the AW, 3 (9%) at the MAS and no one at the MA.\Question: Does the tissue Doppler imaging derived post-systolic velocity notch originate at the aortic annulus?


Output: The AA represents the site of the earliest onset and maximal amplitude of the PSN on the longitudinal velocity curve suggesting its mechanism to be that of an energy release at the instant of the aortic valve closure causing an apically directed acceleration of the myocardium. A substantial number of healthy subjects exhibit a second PSN spike predominantly at the level of the AA. Its mechanism remains to be elucidated.