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NO released from the endothelium as a gas initiates a signaling cascade involving the activation of soluble guanylate cyclase (sGC) to increase cyclic guanosine monophosphate (cGMP) synthesis [22] (Figure 1)

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The discovery of RET mutations and insight gained from the correlation of clinical phenotype with specific molecular changes has led to the current classification system (Table 1) (89)

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