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Patients were stratified into first-line (n=149) and higher-line (n=82) groups

Recon 2.04 was chosen as it outperformed Recon3D [26] for essential genes prediction in previous studies [27]

Fortunately, in view of the potential threat to oxygen delivery that methemoglobin poses, there are protective mechanisms that ensure that most of this methemoglobin is converted back to hemoglobin, so that no more than 1-2 % of total hemoglobin is normally present as methemoglobin