{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:47:59Z","timestamp":1774003679656,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005722","name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005722","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Photochem Photobiol Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor, characterized by infiltrative growth, resistance to chemotherapy and radiotherapy, and an immune-suppressive microenvironment. Interstitial Photodynamic Therapy (iPDT), which involves oral ALA administration and localized light activation, offers a promising approach by killing tumor cells, disrupting tumor vasculature, and stimulating the immune response. However, iPDT faces limitations due to the blood\u2013brain barrier (BBB), insufficient irradiation of satellite and margin tumors, hypoxia within the tumor microenvironment, and glioma cell repair mechanisms. These factors collectively contribute to the suboptimal efficacy of iPDT, emphasizing the need for combined therapeutic strategies to improve outcomes. Some in-vitro research on D, L-methadone, which enhances chemotherapy and ALA-PDT, has caught our interest, although it remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The levels of the \u03bc-opioid receptor (MOR) were measured in multiple GBM cell lines. Multiple GBM cell lines (A172, U251, GB14) were treated with 2.5\u00a0\u00b5g\/ml and 10\u00a0\u00b5g\/ml D, L-methadone in combination with sublethal-dose ALA-PDT to mimic the limitations of PDT. A MOR antagonist, naloxone (NAL), was used to inhibit the potential role of methadone. Cell viability, apoptosis, PpIX, and ROS were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The expression level of MOR in GBM cell lines was low. In the A172 cell line, 10\u00a0\u00b5g\/ml methadone enhanced sublethal-dose ALA-PDT-induced apoptosis; however, in the U251 and GB14 cell lines, neither 2.5\u00a0\u00b5g\/ml methadone nor 10\u00a0\u00b5g\/ml methadone could enhance ALA-PDT-induced apoptosis. The viability of the three cell lines was unaffected by methadone combined with ALA-PDT. No reversal effect of naloxone on methadone was observed. Data show that methadone did not significantly enhance PpIX accumulation or ROS generation when combined with ALA-PDT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A general sensitizing effect of methadone on ALA-PDT was not observed in this in vitro experiment involving multiple GBM cell lines. The sensitizing effect of methadone on ALA-PDT may depend on the specific cell line used. Therefore, the recommendation to use methadone as a sensitizer for ALA-PDT in the treatment of GBM should be made with caution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43630-026-00863-7","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:39:29Z","timestamp":1773225569000},"page":"529-538","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the impact of D, L-methadone on ALA-PDT in multiple glioblastoma cell lines"],"prefix":"10.1007","volume":"25","author":[{"given":"Linglin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Pohla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"R\u00fchm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert","family":"Stepp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Sroka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"issue":"9","key":"863_CR1","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1001\/jamaoncol.2018.1789","volume":"4","author":"QT Ostrom","year":"2018","unstructured":"Ostrom, Q. T., Cote, D. J., Ascha, M., Kruchko, C., & Barnholtz-Sloan, J. S. (2018). Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncology, 4(9), 1254\u20131262. https:\/\/doi.org\/10.1001\/jamaoncol.2018.1789","journal-title":"JAMA Oncology"},{"issue":"12 Suppl 2","key":"863_CR2","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noad149","volume":"25","author":"QT Ostrom","year":"2023","unstructured":"Ostrom, Q. T., Price, M., Neff, C., Cioffi, G., Waite, K. A., Kruchko, C., & Barnholtz-Sloan, J. S. (2023). CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020. Neuro-Oncology, 25(12 Suppl 2), iv1\u2013iv99. https:\/\/doi.org\/10.1093\/neuonc\/noad149","journal-title":"Neuro-Oncology"},{"issue":"7","key":"863_CR3","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1001\/jama.2023.0023","volume":"329","author":"LR Schaff","year":"2023","unstructured":"Schaff, L. R., & Mellinghoff, I. K. (2023). Glioblastoma and other primary brain malignancies in adults: A review. JAMA, 329(7), 574\u2013587. https:\/\/doi.org\/10.1001\/jama.2023.0023","journal-title":"JAMA"},{"issue":"6","key":"863_CR4","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1097\/wco.0000000000001320","volume":"37","author":"CM Fukushima","year":"2024","unstructured":"Fukushima, C. M., & de Groot, J. (2024). Updates for newly diagnosed and recurrent glioblastoma: A review of recent clinical trials. Current Opinion in Neurology, 37(6), 666\u2013671. https:\/\/doi.org\/10.1097\/wco.0000000000001320","journal-title":"Current Opinion in Neurology"},{"key":"863_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105780","volume":"171","author":"W Wu","year":"2021","unstructured":"Wu, W., Klockow, J. L., Zhang, M., Lafortune, F., Chang, E., Jin, L., Wu, Y., & Daldrup-Link, H. E. (2021). Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacological Research, 171, Article 105780. https:\/\/doi.org\/10.1016\/j.phrs.2021.105780","journal-title":"Pharmacological Research"},{"key":"863_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13111536","author":"RS Angom","year":"2023","unstructured":"Angom, R. S., Nakka, N. M. R., & Bhattacharya, S. (2023). Advances in glioblastoma therapy: An update on current approaches. Brain Sciences. https:\/\/doi.org\/10.3390\/brainsci13111536","journal-title":"Brain Sciences"},{"issue":"5","key":"863_CR7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/lsm.22933","volume":"50","author":"H Stepp","year":"2018","unstructured":"Stepp, H., & Stummer, W. (2018). 5-ALA in the management of malignant glioma. Lasers in Surgery and Medicine, 50(5), 399\u2013419. https:\/\/doi.org\/10.1002\/lsm.22933","journal-title":"Lasers in Surgery and Medicine"},{"issue":"4","key":"863_CR8","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1080\/1061186x.2024.2431676","volume":"33","author":"S Sharma","year":"2025","unstructured":"Sharma, S., Gone, G. B., Roychowdhury, P., Kim, H. S., Chung, S. J., Kuppusamy, G., & De, A. (2025). Photodynamic and sonodynamic therapy synergy: Mechanistic insights and cellular responses against glioblastoma multiforme. Journal of Drug Targeting, 33(4), 458\u2013472. https:\/\/doi.org\/10.1080\/1061186x.2024.2431676","journal-title":"Journal of Drug Targeting"},{"issue":"3","key":"863_CR9","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s11060-019-03103-4","volume":"141","author":"K Mahmoudi","year":"2019","unstructured":"Mahmoudi, K., Garvey, K. L., Bouras, A., Cramer, G., Stepp, H., Jesu Raj, J. G., Bozec, D., Busch, T. M., & Hadjipanayis, C. G. (2019). 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. Journal of Neuro-Oncology, 141(3), 595\u2013607. https:\/\/doi.org\/10.1007\/s11060-019-03103-4","journal-title":"Journal of Neuro-Oncology"},{"key":"863_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2021.102492","volume":"36","author":"HA Leroy","year":"2021","unstructured":"Leroy, H. A., Gu\u00e9rin, L., Lecomte, F., Baert, G., Vignion, A. S., Mordon, S., & Reyns, N. (2021). Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review. Photodiagnosis and Photodynamic Therapy, 36, Article 102492. https:\/\/doi.org\/10.1016\/j.pdpdt.2021.102492","journal-title":"Photodiagnosis and Photodynamic Therapy"},{"issue":"1","key":"863_CR11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s11060-023-04284-9","volume":"162","author":"S Quach","year":"2023","unstructured":"Quach, S., Schwartz, C., Aumiller, M., Foglar, M., Schmutzer, M., Katzendobler, S., El Fahim, M., Forbrig, R., Bochmann, K., Egensperger, R., Sroka, R., Stepp, H., R\u00fchm, A., & Thon, N. (2023). Interstitial photodynamic therapy for newly diagnosed glioblastoma. Journal of Neuro-Oncology, 162(1), 217\u2013223. https:\/\/doi.org\/10.1007\/s11060-023-04284-9","journal-title":"Journal of Neuro-Oncology"},{"key":"863_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15092603","author":"M Foglar","year":"2023","unstructured":"Foglar, M., Aumiller, M., Bochmann, K., Buchner, A., El Fahim, M., Quach, S., Sroka, R., Stepp, H., Thon, N., Forbrig, R., & R\u00fchm, A. (2023). Interstitial photodynamic therapy of glioblastomas: A long-term follow-up analysis of survival and volumetric MRI data. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers15092603","journal-title":"Cancers (Basel)"},{"key":"863_CR13","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-020-03618-1","author":"CW Teng","year":"2020","unstructured":"Teng, C. W., Amirshaghaghi, A., Cho, S. S., Cai, S. S., De Ravin, E., Singh, Y., Miller, J., Sheikh, S., Delikatny, E., Cheng, Z., Busch, T. M., Dorsey, J. F., Singhal, S., Tsourkas, A., & Lee, J. Y. K. (2020). Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster. Journal of Neuro-Oncology. https:\/\/doi.org\/10.1007\/s11060-020-03618-1","journal-title":"Journal of Neuro-Oncology"},{"key":"863_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081767","author":"S Lietke","year":"2021","unstructured":"Lietke, S., Schmutzer, M., Schwartz, C., Weller, J., Siller, S., Aumiller, M., Heckl, C., Forbrig, R., Niyazi, M., Egensperger, R., Stepp, H., Sroka, R., Tonn, J. C., R\u00fchm, A., & Thon, N. (2021). Interstitial photodynamic therapy using 5-ALA for malignant glioma recurrences. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers13081767","journal-title":"Cancers (Basel)"},{"issue":"5","key":"863_CR15","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/lsm.22620","volume":"49","author":"HA Leroy","year":"2017","unstructured":"Leroy, H. A., Vermandel, M., Vignion-Dewalle, A. S., Leroux, B., Maurage, C. A., Duhamel, A., Mordon, S., & Reyns, N. (2017). Interstitial photodynamic therapy and glioblastoma: Light fractionation in a preclinical model. Lasers in Surgery and Medicine, 49(5), 506\u2013515. https:\/\/doi.org\/10.1002\/lsm.22620","journal-title":"Lasers in Surgery and Medicine"},{"issue":"5","key":"863_CR16","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1007\/s10103-017-2225-7","volume":"32","author":"MD Stringasci","year":"2017","unstructured":"Stringasci, M. D., Fortunato, T. C., Moriyama, L. T., Filho, J. D. V., Bagnato, V. S., & Kurachi, C. (2017). Interstitial PDT using diffuser fiber-investigation in phantom and in vivo models. Lasers in Medical Science, 32(5), 1009\u20131016. https:\/\/doi.org\/10.1007\/s10103-017-2225-7","journal-title":"Lasers in Medical Science"},{"key":"863_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13030580","author":"JI Traylor","year":"2021","unstructured":"Traylor, J. I., Pernik, M. N., Sternisha, A. C., McBrayer, S. K., & Abdullah, K. G. (2021). Molecular and metabolic mechanisms underlying selective 5-aminolevulinic acid-induced fluorescence in gliomas. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers13030580","journal-title":"Cancers (Basel)"},{"issue":"10","key":"863_CR18","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.4161\/cc.28493","volume":"13","author":"C Friesen","year":"2014","unstructured":"Friesen, C., Hormann, I., Roscher, M., Fichtner, I., Alt, A., Hilger, R., Debatin, K. M., & Miltner, E. (2014). Opioid receptor activation, triggering downregulation of cAMP, improves the effectiveness of anti-cancer drugs in the treatment of glioblastoma. Cell Cycle, 13(10), 1560\u20131570. https:\/\/doi.org\/10.4161\/cc.28493","journal-title":"Cell Cycle"},{"issue":"3","key":"863_CR19","doi-asserted-by":"publisher","DOI":"10.2217\/cns-2018-0006","volume":"7","author":"K Brawanski","year":"2018","unstructured":"Brawanski, K., Brockhoff, G., Hau, P., Vollmann-Zwerenz, A., Freyschlag, C., Lohmeier, A., Riemenschneider, M. J., Thome, C., Brawanski, A., & Proescholdt, M. A. (2018). Efficacy of D, L-methadone in the treatment of glioblastoma in vitro. CNS Oncology, 7(3), Article CNS18. https:\/\/doi.org\/10.2217\/cns-2018-0006","journal-title":"CNS Oncology"},{"key":"863_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/biom10060917","author":"T Vatter","year":"2020","unstructured":"Vatter, T., Klumpp, L., Ganser, K., Stransky, N., Zips, D., Eckert, F., & Huber, S. M. (2020). Against repurposing methadone for glioblastoma therapy. Biomolecules. https:\/\/doi.org\/10.3390\/biom10060917","journal-title":"Biomolecules"},{"issue":"6","key":"863_CR21","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1007\/s00280-019-03816-3","volume":"83","author":"H Oppermann","year":"2019","unstructured":"Oppermann, H., Matusova, M., Glasow, A., Dietterle, J., Baran-Schmidt, R., Neumann, K., Meixensberger, J., & Gaunitz, F. (2019). D, L-methadone does not improve the efficacy of radio- and chemotherapy in vitro for glioblastoma. Cancer Chemotherapy and Pharmacology, 83(6), 1017\u20131024. https:\/\/doi.org\/10.1007\/s00280-019-03816-3","journal-title":"Cancer Chemotherapy and Pharmacology"},{"issue":"10","key":"863_CR22","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201800468","volume":"12","author":"L Shi","year":"2019","unstructured":"Shi, L., Buchner, A., Pohla, H., Pongratz, T., R\u00fchm, A., Zimmermann, W., Gederaas, O. A., Zhang, L., Wang, X., Stepp, H., & Sroka, R. (2019). Methadone enhances the effectiveness of 5-aminolevulinic acid-based photodynamic therapy for squamous cell carcinoma and glioblastoma in vitro. Journal of Biophotonics, 12(10), Article e201800468. https:\/\/doi.org\/10.1002\/jbio.201800468","journal-title":"Journal of Biophotonics"},{"issue":"10","key":"863_CR23","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1515\/bmte.1995.40.10.272","volume":"40","author":"A Knappe","year":"1995","unstructured":"Knappe, A., Beyer, W., Riesenberg, R., Schneede, P., Sroka, R., Uns\u00f6ld, E., & Valet, G. (1995). [Computer-controlled laser irradiation unit for studies of light-induced processes in cell cultures]. Biomedical Engineering = Biomedizinische Technik, 40(10), 272\u2013275. https:\/\/doi.org\/10.1515\/bmte.1995.40.10.272. (Computergesteuerte Laserbestrahlungseinheit f\u00fcr Untersuchungen lichtinduzierter Prozesse an Zellkulturen.).","journal-title":"Biomedical Engineering = Biomedizinische Technik"},{"issue":"6","key":"863_CR24","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1111\/j.1751-1097.2010.00799.x","volume":"86","author":"A Johansson","year":"2010","unstructured":"Johansson, A., Palte, G., Schnell, O., Tonn, J. C., Herms, J., & Stepp, H. (2010). 5-Aminolevulinic acid-induced protoporphyrin IX levels in the tissue of human malignant brain tumors. Photochemistry and Photobiology, 86(6), 1373\u20131378. https:\/\/doi.org\/10.1111\/j.1751-1097.2010.00799.x","journal-title":"Photochemistry and Photobiology"},{"issue":"3","key":"863_CR25","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1021\/nn3058642","volume":"7","author":"CS Jin","year":"2013","unstructured":"Jin, C. S., Lovell, J. F., Chen, J., & Zheng, G. (2013). Ablation of hypoxic tumors with dose-equivalent photothermal, but not photodynamic, therapy using a nanostructured porphyrin assembly. ACS Nano, 7(3), 2541\u20132550. https:\/\/doi.org\/10.1021\/nn3058642","journal-title":"ACS Nano"},{"issue":"7","key":"863_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1117\/1.Jbo.23.7.075006","volume":"23","author":"N Honda","year":"2018","unstructured":"Honda, N., Ishii, K., Kajimoto, Y., Kuroiwa, T., & Awazu, K. (2018). Determination of optical properties of human brain tumor tissues from 350 to 1000 nm to investigate the cause of false negatives in fluorescence-guided resection with 5-aminolevulinic acid. Journal of Biomedical Optics, 23(7), 1\u201310. https:\/\/doi.org\/10.1117\/1.Jbo.23.7.075006","journal-title":"Journal of Biomedical Optics"},{"key":"863_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/ph14020138","author":"B Myrzakhmetov","year":"2021","unstructured":"Myrzakhmetov, B., Arnoux, P., Mordon, S., Acherar, S., Tsoy, I., & Frochot, C. (2021). Photophysical properties of protoporphyrin IX, pyropheophorbide-a, and Photofrin(\u00ae) in different conditions. Pharmaceuticals (Basel). https:\/\/doi.org\/10.3390\/ph14020138","journal-title":"Pharmaceuticals (Basel)"},{"issue":"10","key":"863_CR28","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1039\/c5pp00132c","volume":"14","author":"JM D\u0105browski","year":"2015","unstructured":"D\u0105browski, J. M., & Arnaut, L. G. (2015). Photodynamic therapy (PDT) of cancer: From local to systemic treatment. Photochemical & Photobiological Sciences, 14(10), 1765\u20131780. https:\/\/doi.org\/10.1039\/c5pp00132c","journal-title":"Photochemical & Photobiological Sciences"},{"key":"863_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/diseases6040085","author":"JL Gordon","year":"2018","unstructured":"Gordon, J. L., Brown, M. A., & Reynolds, M. M. (2018). Cell-based methods for determination of efficacy for candidate therapeutics in the clinical management of cancer. Diseases. https:\/\/doi.org\/10.3390\/diseases6040085","journal-title":"Diseases"}],"container-title":["Photochemical &amp; Photobiological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43630-026-00863-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43630-026-00863-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43630-026-00863-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:30:25Z","timestamp":1773995425000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43630-026-00863-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["863"],"URL":"https:\/\/doi.org\/10.1007\/s43630-026-00863-7","relation":{},"ISSN":["1474-905X","1474-9092"],"issn-type":[{"value":"1474-905X","type":"print"},{"value":"1474-9092","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"5 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}