Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: Context: Is a perioperative metastatic screening programme indicated in patients presenting with primary operable breast cancer and no signs of distant metastases?', 'The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analysed in 1 076 patients with an operable breast cancer and no clinical signs of metastases.', 'Staging examinations revealed 30 (2.8 %) distant metastases, 130 (12.1 %) suspect findings and excluded metastases in 916 (85.1 %) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4 %) and excluded them in 123 (94.6 %) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing tumor size (pT < or = 2.0 cm: 1.6 %, pT 2.1-5.0 cm: 3.0 %, respectively pT > 5.0 cm: 15.1 %; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.4 %, pN1-3 +: 1.8 %, pN4-9 +: 4.0 %, pN > 10 +: 12.5 %; p < 0.001). Due to false positive findings 123 (11.4 %) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1 076 patients saves costs of at least euro 259,366.68.
Answer: In breast cancer patients without clinical signs of tumor spread perioperative screening for metastases is not warranted because of low frequency of metastases, false positive findings, missing therapeutic consequences and high costs.

Answer: Is [ A perioperative screening for metastatic disease indicated in patients with primary breast cancer and no clinical signs of tumor spread ]?


Question: Context: Nociceptin/orphanin FQ (N/OFQ) receptor (NOP) agonists produce anxiolytic-like effects in rodents while antagonists promote antidepressant-like effects. The aim of this study was to investigate the effect on anxiety and depression of NOP receptor partial agonists such as the peptides [F/G]N/OFQ(1-13)NH2 and UFP-113 and the non-peptide AT-090.', 'In\xa0vitro AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 were tested for their ability to promote NOP/G-protein and NOP/β-arrestin 2 interaction, using a bioluminescence resonance energy transfer assay. In\xa0vivo, they were tested in mice in the elevated plus maze (EPM) and in the forced swim (FST) tests. NOP partial agonists effects were systematically compared to those of full agonists (N/OFQ and Ro 65-6570) and antagonists (UFP-101 and SB-612111).', 'In\xa0vitro, AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 promoted NOP/G protein interaction, with maximal effects lower than those evoked by N/OFQ and Ro 65-6570. AT-090 behaved as a NOP partial agonist also in inducing β-arrestin 2 recruitment, while UFP-113 and [F/G]N/OFQ(1-13)NH2 were inactive in this assay. In\xa0vivo, AT-090 induced anxiolytic-like effects in the EPM but was inactive in the FST. Opposite results were obtained with UFP-113 and [F/G]N/OFQ(1-13)NH2.
Answer: NOP ligands producing similar effects on NOP/G protein interaction (partial agonism) but showing different effects on β-arrestin 2 recruitment (partial agonism vs antagonism) elicited different actions on anxiety and mood. These results suggest that the action of a NOP ligand on emotional states is better predicted based on its β-arrestin 2 rather than G-protein efficacy.

Answer: Does beta-arrestin 2 rather than G protein efficacy determine the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands?


Question: Context: The effective mechanisms of microRNAs (miRNAs) functions as oncogenes or tumour suppressors in human hepatocellular carcinoma (HCC) are still obscure. Here, we investigated the function and expression of miR-1228 in HCC.', 'The role of miR-1228 in HCC was determined by colony formation, transwell, and nude mice xenograft experiments. miR-1228 target gene were identified by EGFP reporter assays, real-time PCR, and western blot analysis. Dual-luciferase reporter assay and real-time PCR analysis are used to examine the regulation of p53.', "miR-1228 promoted proliferation and metastasis, and facilitated the transition of cell cycle in hepatoma cells. miR-1228 downregulated p53 expression by binding to its 3'UTR. The ectopic expression of p53 abrogated the phenotypes induced by miR-1228. An inverse correlation existed between miR-1228 and p53 expression in hepatoma tissues compared with the adjacent tissues and three hepatoma cell lines. Moreover, we found that p53 suppressed the expression and promoter activity of miR-1228.
Answer: miR-1228 functions as an oncogene by promoting cell cycle progression and cell mobility and negatively regulates the expression of p53. p53 downregulation in turn leads to an increase in miR-1228 expression, thereby forming a positive feedback loop that contributes to cancerogenesis in HCC.

Answer:
Does miR-1228 promote the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop?