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Abbreviations SCD: Sickle cell diseases RBC: Red blood cells WHO: World Health Organization HPLC: High-performance liquid chromatography RNA: Ribonucleic acid ERK12: Extracellular signal-regulated protein kinase DNA: Deoxynucleic acid WBC: White blood cells AUC: Area under curve Cmax: Maximum concentration Hb: Hemoglobin TEAEs: Treatment-emergent adverse event FDA: Food and drug administration ICER: Institution for clinical and economic review HU: Hydroxyurea EMEA: European medical agency cGMP: Cyclic GMP VOC: Vaso-occlusive crisis NAD: Nicotinamide adenine dinucleotide BMT: Bone marrow transplant GVHD: Graft versus host disease HLA: Human leukocyte antigen ADP: Adenosine diphosphate References Lagunju I, Brown BJ, Oyinlade AO et al (2019) Annual stroke incidence in Nigerian children with sickle cell disease and elevated TCD velocities treated with hydroxyurea

Sulfur index analysis (sulfur metabolomics) Sulfur index analysis was carried out using S -bimanyl derivatives through LC MS/MS (Shimadzu Nexera UHPLC system with on-line LCMS 8040, Kyoto, Japan), as previously described 59,60,61,62