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To relax the log(linear) assumption usually applied to continuous doseresponse risk and make the estimates robust to the placement of spline knots, we used an ensemble spline approach to fit the functional form of the doseresponse relationship

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This might be the ability of nicotine to reduce the turnover and release of dopamine through occupying mu or kappa receptors of endorphins or through cholinergic receptors for nicotine[19,20] presented on dopaminergic cells