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.
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Question: Context: 5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.', 'To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations.', 'DNA was obtained from patients who underwent TLND and had ⩾2 positive nodes, largest node >3cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.', 'Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p=0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.\Question: Is bRAF mutation status an independent prognostic factor for resected stage IIIB and IIIC melanoma : implications for melanoma staging and adjuvant therapy?

Answer: Patients with BRAF mutations experienced rapid progression of metastatic disease with locoregional recurrence rarely seen in isolation, supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK inhibitors post-TLND.


Question: Context: Studies over many years have demonstrated that preoptimization and attention to appropriate perioperative care is associated with a substantial decrease in surgical mortality. This review discusses ways in which patient preparation and perioperative support can minimize surgical mortality and morbidity.', 'Scoring systems continue to be developed in order to classify categories of surgical risk. Objective physiologically based assessments can also identify high-risk groups of patients. Debate continues over the indications for specific interventions such as beta-blockade or statin therapy. There is continuing interest in perioperative optimization of oxygen delivery. A multimodality approach paying attention to a range of possible interventions appears to be beneficial. Audit, training, experience and a sufficient volume of procedures are all factors associated with surgical mortality.\Question: Does excellent anaesthesia need patient preparation and postoperative support to influence outcome?

Answer: The provision of a high-quality service throughout the perioperative period is vital for a successful outcome. Patients need to be assessed well before major elective surgery to determine if they fall into a high-risk category. Some patients may benefit from a change in management. Postoperatively, critical-care support should be available backed by level 1 (enhanced ward) care with input from outreach or medical emergency teams 24 hours per day, seven days a week.


Question: Context: Dacts are multi-domain adaptor proteins. They have been implicated in Wnt and Tgfβ signaling and serve as a nodal point in regulating many cellular activities. Dact genes have so far only been identified in bony vertebrates. Also, the number of Dact genes in a given species, the number and roles of protein motifs and functional domains, and the overlap of gene expression domains are all not clear. To address these problems, we have taken an evolutionary approach, screening for Dact genes in the animal kingdom and establishing their phylogeny and the synteny of Dact loci. Furthermore, we performed a deep analysis of the various Dact protein motifs and compared the expression patterns of different Dacts.', 'Our study identified previously not recognized dact genes and showed that they evolved late in the deuterostome lineage. In gnathostomes, four Dact genes were generated by the two rounds of whole genome duplication in the vertebrate ancestor, with Dact1/3 and Dact2/4, respectively, arising from the two genes generated during the first genome duplication. In actinopterygians, a further dact4r gene arose from retrotranscription. The third genome duplication in the teleost ancestor, and subsequent gene loss in most gnathostome lineages left extant species with a subset of Dact genes. The distribution of functional domains suggests that the ancestral Dact function lied with Wnt signaling, and a role in Tgfβ signaling may have emerged with the Dact2/4 ancestor. Motif reduction, in particular in Dact4, suggests that this protein may counteract the function of the other Dacts. Dact genes were expressed in both distinct and overlapping domains, suggesting possible combinatorial function.\Question: Are dact genes chordate specific regulators at the intersection of Wnt and Tgf-β signaling pathways?

Answer:
The gnathostome Dact gene family comprises four members, derived from a chordate-specific ancestor. The ability to control Wnt signaling seems to be part of the ancestral repertoire of Dact functions, while the ability to inhibit Tgfβ signaling and to carry out specialized, ortholog-specific roles may have evolved later. The complement of Dact genes coexpressed in a tissue provides a complex way to fine-tune Wnt and Tgfβ signaling. Our work provides the basis for future structural and functional studies aimed at unraveling intracellular regulatory networks.