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: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.', 'Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.
Answer: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.

Answer: Does dll1 haploinsufficiency in adult mice lead to a complex phenotype affecting metabolic and immunological processes?


Question: Context: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention.', 'One hundred twelve subjects (48 men and 64 women; age, 46 +/- 11 years; BMI, 29.2 +/- 4.4 kg/m(2)) were studied after a follow up-time of 264 +/- 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy.', 'Cross-sectionally high VAT (r = -0.22, p = 0.02) and high LF (r = -0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (-3.0%), VAT (-12.0%), and LF (-33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = -0.41), VAT (r = -0.28), and LF (r = -0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = -0.28, p = 0.01) and high LF (r = -0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity.
Answer: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.

Answer: Are high visceral fat mass and high liver fat associated with resistance to lifestyle intervention?


Question: Context: To evaluate the significance of contrast-enhanced ultrasound (CEUS) examination in differential diagnosis of malignant and benign breast lesions.', 'Seventy-one patients with seventy-six breast tumors are selected randomly. CEUS examinations were performed before and after bolus injection of the contrast agent SonoVue (Bracco, Milan, Italy). Specific sonographic quantification software, Qontrast, was adopted to determine the morphology of vessels. Wash-in and wash-out parameters of each lesion were assessed for both procedures.', 'The final histopathological findings distinguished 45 malignant and 31 benign from all of the lesions. Following SonoVue administration different perfusion phases could be identified: early (0-1min), mid (1-4min) and late (4-6min) phases. In the early phase, CEUS identified 91.1% of malignant tumors characterized by a claw-shaped enhancement, while 83.9% of benign tumors had a homogeneous enhancement, with a statistically significant difference between the two enhancement patterns (chi(2)=43.16, P<0.01). Moreover, contrast medium persistence in the late phase was helpful in the identification of benign and malignant tumors (chi(2)=46.88, P<0.01): contrast medium was present in 88.9% of malignant tumors, while in only 9.7% of the benign tumors. The study showed that various parametric imaging color maps for peak intensity and time to peak were mostly suggestive of malignancy, while quite uniform peak intensity and time to peak of color maps were the characteristic of benign tumors. The study also found that malignant lesions presented with a higher maximum intensity signal than benign ones (P<0.05) on the time-intensity curves.
Answer: CEUS cooperating with conventional US shows improved accuracy in differentiating between malignant and benign breast tumors. It could be a reliable diagnostic method of breast lesions.

Answer:
Is contrast-enhanced ultrasound helpful in the differentiation of malignant and benign breast lesions?