{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:57:28Z","timestamp":1781650648949,"version":"3.54.5"},"reference-count":97,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sickle Cell Disease (SCD) is a common autosomal recessive hemoglobinopathy caused by a point mutation in the \u03b2-globin gene, leading to aberrant production of Hemoglobin S (HbS). The pathophysiological process initiated by this mutation triggers a cascade of symptoms, including erythrocyte sickling, vasococcus occlusions, chronic hemolysis, and widespread inflammatory reactions, culminating in a multitude of clinical complications. Unfortunately, in resource-poor regions, the increasing incidence of SCD outstrips the capabilities of public healthcare systems, thereby creating a dire and urgent requirement for readily available and optimized therapies. Hydroxyurea (HU) has proven itself as a definitive treatment that promotes fetal hemoglobin production, prevents clinical complications, and thereby provides a promising, cost-effective alternative to chronic blood transfusions. Recent findings indicate that microRNAs (miRNAs) play a pivotal role in regulating hematopoiesis and globin switching, thereby making them fundamental mediators and targets of HU therapy. In this review, we explore beyond the traditional frontiers of HU therapy by critically evaluating its rationale as a two-way modifier of the miRNA-scope, which affects crosstalk within a ceRNA network, promotes upregulation of desirable miRNAs, and also triggers HU-induced adaptive miRs that can potentially destabilize therapeutic responses or even induce adverse reactions. More importantly, this review proposes a new, comprehensive conceptual framework to overcome and explore the constraints of monotherapy. In a nimble review of prior findings, we clarify and establish which specific alterations of HU-induced miRs would form a rational basis and hypotensive stimulus of mimicking therapy and thereby differentiate which specific alterations of upregulated or downregulated miRs should form a systemic basis of antagomiring therapy and thus lay out a specific and comprehensive roadmap of combinatorial medicine and therapy in managing SCD.<\/jats:p>","DOI":"10.1007\/s00277-026-06969-3","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:18:13Z","timestamp":1776813493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of hydroxyurea in modulating miRNA expression in sickle cell disease: molecular mechanisms and therapeutic implications"],"prefix":"10.1007","volume":"105","author":[{"given":"Faezeh","family":"Mirzaee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Khamoushi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roghayeh","family":"Dolati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhosein","family":"Abbasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"6969_CR1","unstructured":"Jon S (2025) Garc\u00edaa, b, c zdenek.racil@gmail.com \u2219 Samanya Mohamed Alid, e \u2219 Renata Hor\u00e1kov\u00e1f, g \u2219 Barbora \u0160ilharov\u00e1e, h \u2219 Ivan Kir\u00edyniad g \u2219 IM. Comprehensive management of sickle cell disease in rural Uganda: a model of integrated care. Lancet"},{"issue":"5","key":"6969_CR2","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/phar.2793","volume":"43","author":"M Dong","year":"2023","unstructured":"Dong M, Ware RE, Dallmann A, Vinks AA (2023) Hydroxyurea treatment for sickle cell anemia during pregnancy and lactation: current evidence and knowledge gaps. Pharmacother J Hum Pharmacol Drug Ther 43(5):419\u2013429","journal-title":"Pharmacother J Hum Pharmacol Drug Ther"},{"key":"6969_CR3","doi-asserted-by":"publisher","first-page":"765958","DOI":"10.3389\/fgene.2021.765958","volume":"12","author":"EC Okocha","year":"2022","unstructured":"Okocha EC, Gyamfi J, Ryan N, Babalola O, Etuk EA, Chianumba R et al (2022) Barriers to therapeutic use of hydroxyurea for sickle cell disease in Nigeria: a cross-sectional survey. Front Genet 12:765958","journal-title":"Front Genet"},{"issue":"1","key":"6969_CR4","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13643-024-02461-z","volume":"13","author":"N Khargekar","year":"2024","unstructured":"Khargekar N, Banerjee A, Athalye S, Mahajan N, Kargutkar N, Tapase P et al (2024) Role of hydroxyurea therapy in the prevention of organ damage in sickle cell disease: a systematic review and meta-analysis. Syst Rev 13(1):60","journal-title":"Syst Rev"},{"issue":"38","key":"6969_CR5","doi-asserted-by":"publisher","first-page":"e35237","DOI":"10.1097\/MD.0000000000035237","volume":"102","author":"C Elendu","year":"2023","unstructured":"Elendu C, Amaechi DC, Alakwe-Ojimba CE, Elendu TC, Elendu RC, Ayabazu CP et al (2023) Understanding Sickle cell disease: Causes, symptoms, and treatment options. Med (Baltim) 102(38):e35237","journal-title":"Med (Baltim)"},{"issue":"21","key":"6969_CR6","doi-asserted-by":"publisher","first-page":"2650","DOI":"10.1182\/blood.V116.21.2650.2650","volume":"116","author":"AL Walker","year":"2010","unstructured":"Walker AL, Steward S, Wang M, Smeltzer MP, Ware RE (2010) Modulation of MicroRNA expression in sickle reticulocytes is associated with hydroxyurea treatment and fetal hemoglobin induction. Blood 116(21):2650","journal-title":"Blood"},{"key":"6969_CR7","doi-asserted-by":"publisher","first-page":"509","DOI":"10.3389\/fgene.2019.00509","volume":"10","author":"K Mnika","year":"2019","unstructured":"Mnika K, Mazandu GK, Jonas M, Pule GD, Chimusa ER, Hanchard NA et al (2019) Hydroxyurea-induced miRNA expression in sickle cell disease patients in Africa. Front Genet 10:509","journal-title":"Front Genet"},{"issue":"19","key":"6969_CR8","doi-asserted-by":"publisher","first-page":"e149539","DOI":"10.1172\/jci.insight.149539","volume":"6","author":"S Dey","year":"2021","unstructured":"Dey S, Udari LM, RiveraHernandez P, Kwon JJ, Willis B, Easler JJ et al (2021) Loss of miR-29a\/b1 promotes inflammation and fibrosis in acute pancreatitis. JCI insight 6(19):e149539","journal-title":"JCI insight"},{"issue":"17","key":"6969_CR9","doi-asserted-by":"publisher","first-page":"9135","DOI":"10.3390\/ijms22179135","volume":"22","author":"WS Lian","year":"2021","unstructured":"Lian WS, Wu RW, Chen YS, Ko JY, Wang SY, Jahr H et al (2021) MicroRNA-29a in osteoblasts represses high-fat diet-mediated osteoporosis and body adiposis through targeting leptin. Int J Mol Sci 22(17):9135","journal-title":"Int J Mol Sci"},{"issue":"1","key":"6969_CR10","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41598-022-25444-3","volume":"13","author":"N Kargutkar","year":"2023","unstructured":"Kargutkar N, Sawant-Mulay M, Hariharan P, Chandrakala S, Nadkarni A (2023) Role of microRNA in hydroxyurea mediated HbF induction in sickle cell anaemia patients. Sci Rep 13(1):369","journal-title":"Sci Rep"},{"issue":"1","key":"6969_CR11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s43042-023-00452-8","volume":"24","author":"AAA Fashami","year":"2023","unstructured":"Fashami AAA, Alemzadeh E, Safarpour H, Miri-Moghaddam E (2023) Effect of hydroxyurea on SP1, LIN28B, IGF2BP3, COL4A5, BCL2, gamma globin genes expression: an in vitro study. Egypt J Med Hum Genet 24(1):72","journal-title":"Egypt J Med Hum Genet"},{"issue":"10","key":"6969_CR12","first-page":"1106","volume":"57","author":"C Cyrus","year":"2021","unstructured":"Cyrus C (2021) The role of miRNAs as therapeutic tools in sickle cell disease. Med (B Aires) 57(10):1106","journal-title":"Med (B Aires)"},{"issue":"7","key":"6969_CR13","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1007\/s12011-023-03897-5","volume":"202","author":"N Najafi","year":"2024","unstructured":"Najafi N, Barangi S, Moosavi Z, Aghaee-Bakhtiari SH, Mehri S, Karimi G (2024) Melatonin attenuates arsenic-induced neurotoxicity in rats through the regulation of miR-34a\/miR-144 in Sirt1\/Nrf2 pathway. Biol Trace Elem Res 202(7):3163\u20133179","journal-title":"Biol Trace Elem Res"},{"key":"6969_CR14","unstructured":"Obeagu E (2024) Oxidative stress in sickle cell anemia: a cellular and molecular perspective. 2:58\u201373"},{"key":"6969_CR15","doi-asserted-by":"publisher","unstructured":"Li B, Zhu X, Ward CM, Starlard-Davenport A, Takezaki M, Berry A et al (2019) MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease. Exp Hematol [Internet]. ;70:85\u201396.e5. Available from: https:\/\/doi.org\/10.1016\/j.exphem.2018.11.002","DOI":"10.1016\/j.exphem.2018.11.002"},{"key":"6969_CR16","doi-asserted-by":"crossref","unstructured":"Sawant M, Colah R, Ghosh K, Nadkarni A (2016) Does HbF induction by hydroxycarbamide work through MIR210 in sickle cell anaemia patients?. Br J Haematol 173(5)","DOI":"10.1111\/bjh.13642"},{"issue":"1","key":"6969_CR17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s40169-016-0092-7","volume":"5","author":"GD Pule","year":"2016","unstructured":"Pule GD, Mowla S, Novitzky N, Wonkam A (2016) Hydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce \u03b3-globin expression: implications for new therapeutic approaches of sickle cell disease. Clin Transl Med 5(1):15","journal-title":"Clin Transl Med"},{"key":"6969_CR18","doi-asserted-by":"publisher","first-page":"112058","DOI":"10.1016\/j.biopha.2021.112058","volume":"142","author":"H Ali","year":"2021","unstructured":"Ali H, Khan F, Musharraf SG (2021) Cilostazol-mediated reversion of \u03b3-globin silencing is associated with a high level of HbF production: A potential therapeutic candidate for \u03b2-globin disorders. Biomed Pharmacother 142:112058","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"6969_CR19","doi-asserted-by":"publisher","first-page":"e2360","DOI":"10.1371\/journal.pone.0002360","volume":"3","author":"SY Chen","year":"2008","unstructured":"Chen SY, Wang Y, Telen MJ, Chi JT (2008) The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. PLoS ONE 3(6):e2360","journal-title":"PLoS ONE"},{"key":"6969_CR20","doi-asserted-by":"crossref","unstructured":"Quinn T, Heath S, Adger WN, Abu M, Butler C, Codjoe SNA et al (2023) Health and wellbeing implications of adaptation to flood risk. Ambio. 20230224th ed. 52(5):952\u201362","DOI":"10.1007\/s13280-023-01834-3"},{"key":"6969_CR21","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1182\/blood-2019-130414","volume":"134","author":"CT Quinn","year":"2019","unstructured":"Quinn CT, Niss O, Pfeiffer A, Korpik J, Bonar H, Reynaud M et al (2019) Pharmacokinetics-Guided Dosing of Hydroxyurea Can Achieve Near-Pancellular Fetal Hemoglobin Expression in Sickle Cell Anemia: F-Cell Analysis As a Benchmark for Disease-Modifying Therapy. Blood 134:892","journal-title":"Blood"},{"issue":"3","key":"6969_CR22","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s00277-020-04390-y","volume":"100","author":"HK Verma","year":"2021","unstructured":"Verma HK, Ratre YK, Bhaskar L, Colombatti R (2021) Erythrocyte microRNAs: a tiny magic bullet with great potential for sickle cell disease therapy. Ann Hematol 100(3):607\u2013614","journal-title":"Ann Hematol"},{"key":"6969_CR23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1182\/blood-2023-187335","volume":"142","author":"LMS Ventura","year":"2023","unstructured":"Ventura LMS, Adimora I, Elliot EC, Fasipe T, Flanagan JM (2023) Clinical and hematopoietic profiles associated with sustained hydroxyurea response for patients with sickle cell disease. Blood 142:17","journal-title":"Blood"},{"issue":"5","key":"6969_CR24","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s40291-022-00589-z","volume":"26","author":"A Starlard-Davenport","year":"2022","unstructured":"Starlard-Davenport A, Gu Q, Pace BS (2022) Targeting genetic modifiers of HBG gene expression in sickle cell disease: the miRNA option. Mol Diagn Ther 26(5):497\u2013509","journal-title":"Mol Diagn Ther"},{"issue":"4","key":"6969_CR25","first-page":"583","volume":"17","author":"N Saki","year":"2016","unstructured":"Saki N, Abroun S, Soleimani M, Kavianpour M, Shahjahani M, Mohammadi-Asl J et al (2016) MicroRNA expression in \u03b2-thalassemia and sickle cell disease: a role in the induction of fetal hemoglobin. Cell J 17(4):583","journal-title":"Cell J"},{"issue":"2","key":"6969_CR26","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1080\/03630269.2017.1290651","volume":"41","author":"MT Hojjati","year":"2017","unstructured":"Hojjati MT, Azarkeivan A, Pourfathollah AA, Amirizadeh N (2017) Comparison of MicroRNAs Mediated in Reactivation of the \u03b3-Globin in \u03b2-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea. Hemoglobin 41(2):110\u2013115","journal-title":"Hemoglobin"},{"key":"6969_CR27","doi-asserted-by":"crossref","unstructured":"Xu L, Jia Y, Yang XH, Han F, Zheng Y, Ni Y et al (2017) MicroRNA-130b transcriptionally regulated by histone H3 deacetylation renders Akt ubiquitination and apoptosis resistance to 6-OHDA. Biochim Biophys Acta (BBA)-Molecular Basis Dis. 1863(6):1678\u20131689","DOI":"10.1016\/j.bbadis.2017.04.012"},{"issue":"3","key":"6969_CR28","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.bbrc.2017.04.099","volume":"487","author":"S Jiang","year":"2017","unstructured":"Jiang S, Teague AM, Tryggestad JB, Chernausek SD (2017) Role of microRNA-130b in placental PGC-1\u03b1\/TFAM mitochondrial biogenesis pathway. Biochem Biophys Res Commun 487(3):607\u2013612","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"6969_CR29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/bjh.18042","volume":"197","author":"Y Sun","year":"2022","unstructured":"Sun Y, Habara A, Le CQ, Nguyen N, Chen R, Murphy GJ et al (2022) Pharmacologic induction of PGC-1\u03b1 stimulates fetal haemoglobin gene expression. Br J Haematol 197(1):97\u2013109","journal-title":"Br J Haematol"},{"issue":"8","key":"6969_CR30","doi-asserted-by":"publisher","first-page":"7546","DOI":"10.3390\/ijms24087546","volume":"24","author":"K Oxendine Harp","year":"2023","unstructured":"Oxendine Harp K, Bashi A, Botchway F, Addo-Gyan D, Tetteh-Tsifoanya M, Lamptey A et al (2023) Sickle cell hemoglobin genotypes affect malaria parasite growth and correlate with exosomal miR-451a and let-7i-5p levels. Int J Mol Sci 24(8):7546","journal-title":"Int J Mol Sci"},{"issue":"4","key":"6969_CR31","first-page":"432","volume":"22","author":"G Shokri","year":"2019","unstructured":"Shokri G, Kouhkan F, Nojehdehi S, Soleimani M, Pourfathollah AA, Zarif MN et al (2019) Simultaneous regulation of miR-451 and miR-191 led to erythroid fate decision of mouse embryonic stem cell. Iran J Basic Med Sci 22(4):432","journal-title":"Iran J Basic Med Sci"},{"issue":"10","key":"6969_CR32","first-page":"1470","volume":"58","author":"C Cyrus","year":"2022","unstructured":"Cyrus C, Vatte C, Al-Nafie A, Chathoth S, Akhtar MS, Darwish M et al (2022) miRNA Expression Associated with HbF in Saudi Sickle Cell Anemia. Med (B Aires) 58(10):1470","journal-title":"Med (B Aires)"},{"issue":"7","key":"6969_CR33","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.3390\/ijms22073626","volume":"22","author":"PL Papasavva","year":"2021","unstructured":"Papasavva PL, Papaioannou NY, Patsali P, Kurita R, Nakamura Y, Sitarou M et al (2021) Distinct miRNA signatures and networks discern fetal from adult erythroid differentiation and primary from immortalized erythroid cells. Int J Mol Sci 22(7):3626","journal-title":"Int J Mol Sci"},{"issue":"20","key":"6969_CR34","first-page":"5664","volume":"118","author":"AL Walker","year":"2011","unstructured":"Walker AL, Steward S, Howard TA, Mortier N, Smeltzer M, Wang YD et al (2011) Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia. Blood J Am Soc Hematol 118(20):5664\u20135670","journal-title":"Blood J Am Soc Hematol"},{"issue":"2","key":"6969_CR35","doi-asserted-by":"publisher","first-page":"dmm049765","DOI":"10.1242\/dmm.049765","volume":"16","author":"A Wonkam","year":"2023","unstructured":"Wonkam A (2023) The future of sickle cell disease therapeutics rests in genomics. Dis Model Mech 16(2):dmm049765","journal-title":"Dis Model Mech"},{"key":"6969_CR36","unstructured":"Agrawal R, Murmu J, Pattnaik S, Kanungo S, Pati S (2023) One Health: navigating plague in Madagascar amidst COVID-19. Infect Dis Poverty [Internet]. ;12(1). Available from: https:\/\/www.scopus.com\/inward\/record.uri?eid=2-s2.0-85159452709&doi=10.1186%2Fs40249-023-01101-3&partnerID=40&md5=401f2a6e91767e82de85cabdb05e1ce2"},{"issue":"4","key":"6969_CR37","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1073\/pnas.1018384108","volume":"108","author":"VG Sankaran","year":"2011","unstructured":"Sankaran VG, Menne TF, \u0160\u0107epanovi\u0107 D, Vergilio JA, Ji P, Kim J et al (2011) MicroRNA-15a and-16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci 108(4):1519\u20131524","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"6969_CR38","doi-asserted-by":"publisher","first-page":"3821","DOI":"10.1038\/s41467-024-47982-2","volume":"15","author":"DA Kretov","year":"2024","unstructured":"Kretov DA, Folkes L, Mora-Martin A, Walawalkar IA, Imrat, Syedah N et al (2024) The miR-144\/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis. Nat Commun 15(1):3821","journal-title":"Nat Commun"},{"issue":"1","key":"6969_CR39","first-page":"53","volume":"6","author":"S Alijani","year":"2014","unstructured":"Alijani S, Alizadeh S, Kazemi A, Khatib ZK, Soleimani M, Rezvani M et al (2014) Evaluation of the effect of miR-26b up-regulation on HbF expression in erythroleukemic K-562 cell line. Avicenna J Med Biotechnol 6(1):53","journal-title":"Avicenna J Med Biotechnol"},{"issue":"2","key":"6969_CR40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s12288-013-0261-4","volume":"30","author":"RK Agrawal","year":"2014","unstructured":"Agrawal RK, Patel RK, Shah V, Nainiwal L, Trivedi B (2014) Hydroxyurea in sickle cell disease: drug review. Indian J Hematol Blood Transfus 30(2):91\u201396","journal-title":"Indian J Hematol Blood Transfus"},{"key":"6969_CR41","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.bcmd.2016.11.002","volume":"62","author":"JR Friedrisch","year":"2016","unstructured":"Friedrisch JR, Sheehan V, Flanagan JM, Baldan A, Summarell CCG, Bittar CM et al (2016) The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil. Blood Cells Mol Dis 62:32\u201337","journal-title":"Blood Cells Mol Dis"},{"issue":"4","key":"6969_CR42","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/ncb2039","volume":"12","author":"J Ding","year":"2010","unstructured":"Ding J, Huang S, Wu S, Zhao Y, Liang L, Yan M et al (2010) Gain of miR-151 on chromosome 8q24. 3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12(4):390\u2013399","journal-title":"Nat Cell Biol"},{"issue":"6","key":"6969_CR43","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/mp.2009.2","volume":"14","author":"R Tabares-Seisdedos","year":"2009","unstructured":"Tabares-Seisdedos R, Rubenstein JLR (2009) Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14(6):563\u2013589","journal-title":"Mol Psychiatry"},{"key":"6969_CR44","doi-asserted-by":"crossref","unstructured":"Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P et al (2007) Micro-RNA profiling in kidney and bladder cancers. Urologic Oncology: Seminars and Original Investigations. Elsevier, pp 387\u2013392","DOI":"10.1016\/j.urolonc.2007.01.019"},{"key":"6969_CR45","volume-title":"Regulators of a regulator: microRNAs in control of regulatory T cell biology","author":"J Dong","year":"2022","unstructured":"Dong J (2022) Regulators of a regulator: microRNAs in control of regulatory T cell biology. University of California, San Diego"},{"key":"6969_CR46","doi-asserted-by":"crossref","unstructured":"Chinwe, Okeke (2022) Ufele Silas ON and OC. HSC and miRNA Regulation with Implication for Foetal Haemoglobin Induction in Beta Haemoglobinopathies. Curr Stem Cell Res Ther","DOI":"10.2174\/1574888X17666220221104711"},{"key":"6969_CR47","unstructured":"Najmaldin S, Saeid A, Masoud S, Maria K, Mohammad S, Javad Mohammadi A et al (2016) MicroRNA expression in beta-Thalassemia and sickle cell disease: a role in the induction of fetal hemoglobin"},{"issue":"1","key":"6969_CR48","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1007\/s11033-024-09981-w","volume":"51","author":"JK Pal","year":"2024","unstructured":"Pal JK, Sur S, Mittal SPK, Dey S, Mahale MP, Mukherjee A (2024) Clinical implications of miRNAs in erythropoiesis, anemia, and other hematological disorders. Mol Biol Rep 51(1):1064","journal-title":"Mol Biol Rep"},{"key":"6969_CR49","doi-asserted-by":"publisher","unstructured":"Kumkhaek C, Zhu J, Aerbajinai W, Ittiprasert W, Liu W, Rodgers GP (2025) Differential MicroRNA Profiles Associated With the Hydroxyurea-Inducible SAR1A Gene. J Hematol [Internet]. 14(3):158\u201363. Available from: https:\/\/doi.org\/10.14740\/jh2021","DOI":"10.14740\/jh2021"},{"issue":"March","key":"6969_CR50","first-page":"1","volume":"13","author":"SR Maruyama","year":"2022","unstructured":"Maruyama SR, Fuzo CA, Oliveira AER, Rogerio LA, Takamiya NT, Pessenda G et al (2022) Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection. Front Immunol 13(March):1\u201318","journal-title":"Front Immunol"},{"issue":"3","key":"6969_CR51","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.18280\/ts.410318","volume":"41","author":"A Deo","year":"2024","unstructured":"Deo A, Pandey I, Khan SS, Mandlik A, Doohan NV, Panchal B (2024) Deep learning-based red blood cell classification for sickle cell anemia diagnosis using hybrid CNN-LSTM model. Trait du signal 41(3):1293","journal-title":"Trait du signal"},{"key":"6969_CR52","doi-asserted-by":"publisher","first-page":"100983","DOI":"10.1016\/j.blre.2022.100983","volume":"56","author":"DC Rees","year":"2022","unstructured":"Rees DC, Brousse VAM, Brewin JN (2022) Determinants of severity in sickle cell disease. Blood Rev 56:100983","journal-title":"Blood Rev"},{"issue":"1","key":"6969_CR53","doi-asserted-by":"publisher","first-page":"3","DOI":"10.31491\/APT.2023.03.107","volume":"5","author":"L He","year":"2023","unstructured":"He L, Li M, Liu Z, Padhiar AA, Zhou G (2023) Senescence of mesenchymal stem cells: implications in extracellular vesicles, miRNAs and their functional and therapeutic potentials. Aging Pathobiol Ther 5(1):3\u201317","journal-title":"Aging Pathobiol Ther"},{"key":"6969_CR54","doi-asserted-by":"publisher","first-page":"148861","DOI":"10.1016\/j.scitotenv.2021.148861","volume":"795","author":"Y Bao","year":"2021","unstructured":"Bao Y, Mehmood K, Saifullah, Yaseen M, Dahlawi S, Abrar MM et al (2021) Global research on the air quality status in response to the electrification of vehicles. Sci Total Env 795:14886120210703rd edn.","journal-title":"Sci Total Env"},{"key":"6969_CR55","unstructured":"Deshuillers PL (2021) Markers of oxidative stress and mature red blood, Cell mirnome in cats with diabetes mellitus. Purdue University Graduate School"},{"key":"6969_CR56","doi-asserted-by":"publisher","first-page":"781815","DOI":"10.3389\/fimmu.2021.781815","volume":"12","author":"S Yuan","year":"2021","unstructured":"Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y et al (2021) miR-223: an immune regulator in infectious disorders. Front Immunol 12:781815","journal-title":"Front Immunol"},{"issue":"3","key":"6969_CR57","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.cell.2007.02.048","volume":"129","author":"T Fukao","year":"2007","unstructured":"Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y et al (2007) An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell 129(3):617\u2013631","journal-title":"Cell"},{"issue":"7","key":"6969_CR58","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1177\/1535370216636725","volume":"241","author":"CM Ward","year":"2016","unstructured":"Ward CM, Li B, Pace BS (2016) Stable expression of miR-34a mediates fetal hemoglobin induction in K562 cells. Exp Biol Med 241(7):719\u2013729","journal-title":"Exp Biol Med"},{"key":"6969_CR59","doi-asserted-by":"crossref","unstructured":"House G (2023) New therapeutic axis in blood malignancies involving microRNAs and JAK\/STAT3 signaling. Authorea Prepr","DOI":"10.22541\/au.170016203.37107299\/v1"},{"key":"6969_CR60","doi-asserted-by":"publisher","unstructured":"Yang F, Ruan H, Li S, Hou W, Qiu Y, Deng L et al (2022) Analysis of circRNAs and circRNA-associated competing endogenous RNA networks in \u03b2-thalassemia. Sci Rep [Internet]. ;12(1):1\u20139. Available from: https:\/\/doi.org\/10.1038\/s41598-022-12002-0","DOI":"10.1038\/s41598-022-12002-0"},{"key":"6969_CR61","doi-asserted-by":"crossref","unstructured":"Chen M, Pan Y, Zhang Y, Zheng J, Zhang S, Lin N et al (2022) Identification of deregulated circular RNA circ-0008102 as novel biomarker in pediatric \u03b2-thalassemia patients. 1\u201324","DOI":"10.21203\/rs.3.rs-1984616\/v1"},{"key":"6969_CR62","doi-asserted-by":"crossref","unstructured":"Habara A (2025) Comparative circRNA profiling in human erythroblasts derived from fetal liver and bone marrow hematopoietic stem cells using public RNA-Seq Data. Int J Mol Sci","DOI":"10.3390\/ijms26178397"},{"key":"6969_CR63","doi-asserted-by":"crossref","unstructured":"Parul Gupta a RK (2025) MicroRNAs in sickle cell disease: a comprehensive review. Gene","DOI":"10.1016\/j.gene.2025.149470"},{"issue":"9","key":"6969_CR64","doi-asserted-by":"publisher","first-page":"411","DOI":"10.14740\/jocmr5245","volume":"16","author":"L Rujito","year":"2024","unstructured":"Rujito L, Wardana T, Siswandari W, Nainggolan IM, Sasongko TH (2024) Potential Use of MicroRNA Technology in Thalassemia Therapy. J Clin Med Res 16(9):411","journal-title":"J Clin Med Res"},{"key":"6969_CR65","doi-asserted-by":"crossref","unstructured":"Wang Y, Li M, Li Z, Chai R, Dong X, Xu H et al (2021) Effect of temperature and its interaction with other meteorological factors on bacillary dysentery in Jilin Province, China. Epidemiol Infect. 20210422nd ed. ;149:e121","DOI":"10.1017\/S0950268821000893"},{"key":"6969_CR66","unstructured":"Sun MA, Sung HM, Kim J, Lee JH, Shim S, Byun YH (2022) Present-day and future projection of East Asian summer monsoon in Coupled Model Intercomparison Project 6 simulations. PLoS One [Internet]. ;17(6 June). Available from: https:\/\/www.scopus.com\/inward\/record.uri?eid=2-s2.0-85131701801&doi=10.1371%2Fjournal.pone.0269267&partnerID=40&md5=f61f6e60adae4afcd4193479c804c8cc"},{"key":"6969_CR67","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1182\/blood-2024-208968","volume":"144","author":"MT Monte","year":"2024","unstructured":"Monte MT, Tozzi L, Palchaudhuri R, Wangweerawong A, Heshmati Y, Schiroli G et al (2024) Delivery of Gene Writers In Vivo to Hematopoietic Stem Cells and T Cells Using Targeted and Untargeted Lipid Nanoparticles (LNP). Blood 144:2197","journal-title":"Blood"},{"key":"6969_CR68","doi-asserted-by":"crossref","unstructured":"Lu Y, Qian C, Huang Y, Ren T, Xie W, Xia N et al (2025) Advancing mRNA vaccines: a comprehensive review of design, delivery, and efficacy in infectious diseases. Int J Biol Macromol. ;145501","DOI":"10.1016\/j.ijbiomac.2025.145501"},{"issue":"1","key":"6969_CR69","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11095-022-03166-5","volume":"39","author":"J Di","year":"2022","unstructured":"Di J, Du Z, Wu K, Jin S, Wang X, Li T et al (2022) Biodistribution and non-linear gene expression of mRNA LNPs affected by delivery route and particle size. Pharm Res 39(1):105\u2013114","journal-title":"Pharm Res"},{"issue":"3","key":"6969_CR70","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.7150\/thno.89380","volume":"14","author":"BP Dhungel","year":"2024","unstructured":"Dhungel BP, Winburn I, da Fonseca Pereira C, Huang K, Chhabra A, Rasko JEJ (2024) Understanding AAV vector immunogenicity: from particle to patient. Theranostics 14(3):1260","journal-title":"Theranostics"},{"issue":"10","key":"6969_CR71","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.3390\/polym17101381","volume":"17","author":"H Zhang","year":"2025","unstructured":"Zhang H, Zhou B, Dong W, Song Y, Hu Q, Zhang H et al (2025) Development and characterization of Adeno-associated virus-loaded coaxial electrospun scaffolds for potential viral vector delivery. Polym (Basel) 17(10):1381","journal-title":"Polym (Basel)"},{"issue":"12","key":"6969_CR72","doi-asserted-by":"publisher","first-page":"4226","DOI":"10.2337\/db15-0521","volume":"64","author":"AD Bhatwadekar","year":"2015","unstructured":"Bhatwadekar AD, Yan Y, Stepps V, Hazra S, Korah M, Bartelmez S et al (2015) MiR-92a corrects CD34\u2009+\u2009cell dysfunction in diabetes by modulating core circadian genes involved in progenitor differentiation. Diabetes 64(12):4226\u20134237","journal-title":"Diabetes"},{"issue":"2","key":"6969_CR73","doi-asserted-by":"publisher","first-page":"52","DOI":"10.5639\/gabij.2020.0902.010","volume":"9","author":"SC Hock","year":"2020","unstructured":"Hock SC, Kian SM, Wah CL (2020) Global challenges in the manufacture, regulation and international harmonization of GMP and quality standards for biopharmaceuticals. Generics Biosimilars Initiat J 9(2):52\u201364","journal-title":"Generics Biosimilars Initiat J"},{"key":"6969_CR74","doi-asserted-by":"crossref","unstructured":"Xu S, Liang D, Wang Q, Cheng Y, Xie D, Gui Y et al (2024) In vivo genome editing of human hematopoietic stem cells for treatment of blood disorders by mRNA delivery. bioRxiv. 2024.10. 28.620445.","DOI":"10.1101\/2024.10.28.620445"},{"key":"6969_CR75","doi-asserted-by":"crossref","unstructured":"Mastriano S, Kanoria S, Rennie W, Liu C, Li D, Cheng J et al (2024) High-Throughput Quantification of miRNA-3\u2032-Untranslated-Region Regulatory Effects. bioRxiv","DOI":"10.1101\/2024.12.05.626985"},{"issue":"1","key":"6969_CR76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/ijmm.2022.5148","volume":"50","author":"J Liu","year":"2022","unstructured":"Liu J, Yang T, Huang Z, Chen H, Bai Y (2022) Transcriptional regulation of nuclear miRNAs in tumorigenesis. Int J Mol Med 50(1):1\u201312","journal-title":"Int J Mol Med"},{"key":"6969_CR77","doi-asserted-by":"publisher","first-page":"1225221","DOI":"10.3389\/fonc.2023.1225221","volume":"13","author":"Y Bai","year":"2023","unstructured":"Bai Y, Li Y, Qin Y, Yang X, Tseng GC, Kim S et al (2023) The microRNA target site profile is a novel biomarker in the immunotherapy response. Front Oncol 13:1225221","journal-title":"Front Oncol"},{"issue":"6","key":"6969_CR78","first-page":"725","volume":"90","author":"IA Volkhin","year":"2025","unstructured":"Volkhin IA, Paremskaia AI, Dashian MA, Smeshnova DS, Pavlov RE, Mityaeva ON et al (2025) Selection of UTRs in mRNA-Based Gene Therapy and Vaccines. Biochem 90(6):725\u2013753","journal-title":"Biochem"},{"key":"6969_CR79","doi-asserted-by":"crossref","unstructured":"Lu S, Khan MA, Setua S, O\u2019Boyle Q, Thangaraju K, Cabrales P et al (2025) Transferrin Purification, Biophysical Characterization, and Lung Biodistribution in Sickle Cell Disease Mice. Biotechnol Bioeng","DOI":"10.1002\/bit.70012"},{"issue":"10","key":"6969_CR80","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1089\/ars.2021.0200","volume":"36","author":"G Zaccagnini","year":"2022","unstructured":"Zaccagnini G, Greco S, Voellenkle C, Gaetano C, Martelli F (2022) miR-210 hypoxamiR in Angiogenesis and Diabetes. Antioxid Redox Signal 36(10):685\u2013706","journal-title":"Antioxid Redox Signal"},{"key":"6969_CR81","doi-asserted-by":"crossref","unstructured":"Alam J, Rahman SZ, Alam S, Hasan A, Haseen MA, Sarfraz M (2024) The Involvement of miR-221\/222 in Vascular Pathophysiology: Implications for Stenting. Cardiol Rev. 10.1097","DOI":"10.1097\/CRD.0000000000000811"},{"issue":"6","key":"6969_CR82","doi-asserted-by":"publisher","first-page":"4419","DOI":"10.3892\/ol.2016.5250","volume":"12","author":"L Zhou","year":"2016","unstructured":"Zhou L, Jiang F, Chen X, Liu Z, Ouyang Y, Zhao W et al (2016) Downregulation of miR-221\/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN. Oncol Lett 12(6):4419\u20134426","journal-title":"Oncol Lett"},{"issue":"1","key":"6969_CR83","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s13046-025-03391-x","volume":"44","author":"MT Martino","year":"2025","unstructured":"Martino MT, Di, Tagliaferri P, Tassone P (2025) MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications. J Exp Clin Cancer Res 44(1):126","journal-title":"J Exp Clin Cancer Res"},{"issue":"2","key":"6969_CR84","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/bph.17302","volume":"182","author":"Z Bereczki","year":"2025","unstructured":"Bereczki Z, Benczik B, Balogh OM, Marton S, Puhl E, P\u00e9terv\u00e1ri M et al (2025) Mitigating off-target effects of small RNAs: conventional approaches, network theory and artificial intelligence. Br J Pharmacol 182(2):340\u2013379","journal-title":"Br J Pharmacol"},{"issue":"14","key":"6969_CR85","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.7150\/ijms.102123","volume":"21","author":"H Qian","year":"2024","unstructured":"Qian H, Maghsoudloo M, Kaboli PJ, Babaeizad A, Cui Y, Fu J et al (2024) Decoding the promise and challenges of miRNA-based cancer therapies: An essential update on miR-21, miR-34, and miR-155. Int J Med Sci 21(14):2781","journal-title":"Int J Med Sci"},{"issue":"5","key":"6969_CR86","doi-asserted-by":"publisher","first-page":"e23528","DOI":"10.1096\/fj.202302028R","volume":"38","author":"YZ Akkaya-Ulum","year":"2024","unstructured":"Akkaya-Ulum YZ, Sen B, Akbaba TH, Balci\u2010Peynircioglu B (2024) InflammamiRs in focus: delivery strategies and therapeutic approaches. FASEB J 38(5):e23528","journal-title":"FASEB J"},{"issue":"1","key":"6969_CR87","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13024-021-00498-5","volume":"16","author":"T Wallach","year":"2021","unstructured":"Wallach T, Mossmann ZJ, Szczepek M, Wetzel M, Machado R, Raden M et al (2021) MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7\/8 ligands that contribute to neurodegeneration. Mol Neurodegener 16(1):80","journal-title":"Mol Neurodegener"},{"issue":"2","key":"6969_CR88","doi-asserted-by":"publisher","first-page":"634","DOI":"10.3390\/molecules28020634","volume":"28","author":"H Zheng","year":"2023","unstructured":"Zheng H, Wu P, Bonnet PA (2023) Recent advances on small-molecule antagonists targeting TLR7. Molecules 28(2):634","journal-title":"Molecules"},{"issue":"605","key":"6969_CR89","doi-asserted-by":"publisher","first-page":"eaaw1347","DOI":"10.1126\/scisignal.aaw1347","volume":"12","author":"M de Marcken","year":"2019","unstructured":"de Marcken M, Dhaliwal K, Danielsen AC, Gautron AS, Dominguez-Villar M (2019) TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection. Sci Signal 12(605):eaaw1347","journal-title":"Sci Signal"},{"key":"6969_CR90","doi-asserted-by":"publisher","first-page":"910654","DOI":"10.3389\/fcimb.2022.910654","volume":"12","author":"N Kano","year":"2022","unstructured":"Kano N, Ong GH, Ori D, Kawai T (2022) Pathophysiological role of nucleic acid-sensing pattern recognition receptors in inflammatory diseases. Front Cell Infect Microbiol 12:910654","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"6969_CR91","doi-asserted-by":"publisher","first-page":"15864","DOI":"10.1038\/s41598-025-00152-w","volume":"15","author":"M Sahun","year":"2025","unstructured":"Sahun M, Bernit E, Atwell S, Hornung A, Charrier AM, Agouti I et al (2025) A novel red blood cell deformability biomarker is associated with hemolysis and vaso-occlusive crises in sickle cell disease. Sci Rep 15(1):15864","journal-title":"Sci Rep"},{"key":"6969_CR92","doi-asserted-by":"publisher","first-page":"454","DOI":"10.3389\/fimmu.2020.00454","volume":"11","author":"E Nader","year":"2020","unstructured":"Nader E, Romana M, Connes P (2020) The red blood cell\u2014inflammation vicious circle in sickle cell disease. Front Immunol 11:454","journal-title":"Front Immunol"},{"issue":"6Supplement","key":"6969_CR93","doi-asserted-by":"publisher","first-page":"3853","DOI":"10.1158\/1538-7445.AM2024-3853","volume":"84","author":"Z Zhao","year":"2024","unstructured":"Zhao Z, Hu B, Deng Y, Soeung M, Genovese G, Li W et al (2024) T cell ferroptosis attenuates antitumor immune responses in sickle cell disease. Cancer Res 84(6Supplement):3853","journal-title":"Cancer Res"},{"key":"6969_CR94","doi-asserted-by":"crossref","unstructured":"Lee JM, Zeng J, Liu P, Nguyen MA, Loustaunau DS, Bauer DE et al (2024) Direct delivery of stabilized Cas-embedded base editors achieves efficient and accurate editing of clinically relevant targets. bioRxiv. ;2024.02. 08.579528.","DOI":"10.1101\/2024.02.08.579528"},{"issue":"5","key":"6969_CR95","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/phar.2792","volume":"43","author":"D Dexter","year":"2023","unstructured":"Dexter D, McGann PT (2023) Hydroxyurea for children with sickle cell disease in sub-Saharan Africa: A summary of the evidence, opportunities, and challenges. Pharmacother J Hum Pharmacol Drug Ther 43(5):430\u2013441","journal-title":"Pharmacother J Hum Pharmacol Drug Ther"},{"issue":"1","key":"6969_CR96","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1186\/s12913-024-11125-6","volume":"24","author":"P Namaganda","year":"2024","unstructured":"Namaganda P, Nantume P, Mubiru KR, Twimukye A, Wiltshire CS (2024) Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study. BMC Health Serv Res 24(1):666","journal-title":"BMC Health Serv Res"},{"key":"6969_CR97","doi-asserted-by":"publisher","unstructured":"van Hooff LC, Merz EM, Kidane Gebremeskel AS, de Jong JA, Burchell GL, Lunshof JE (2025) Balancing benefits and burdens: a systematic review on ethical and social dimensions of gene and cell therapies for hereditary blood diseases. BMC Med Ethics [Internet]. 26(1). Available from: https:\/\/doi.org\/10.1186\/s12910-025-01188-3","DOI":"10.1186\/s12910-025-01188-3"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06969-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-06969-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06969-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:31:19Z","timestamp":1781649079000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-06969-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":97,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["6969"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-06969-3","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"assertion":[{"value":"18 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"During the preparation of this work, the author(s) used ChatGPT to enhance the clarity and grammar of the writing. After using this tool\/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the publication\u2019s content.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"261"}}