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Simulation modeling with sensitivity analyses that examine all the states and transition pathways in the state transition model (Figure 3) show that the gateway effect would have to be implausibly large to increase the net public health harm (20

Indeed, while nicotine in normal doses is not as dangerous as perceived, the Surgeon Generals report in 2014, The Health Consequences of Smoking50 Years of Progress, surmised that nicotine has acute toxicity at high doses and activates biological pathways that upsurge the risk of disease

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