{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:14:23Z","timestamp":1785406463823,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InTechThrace","award":["MIS Code 5047285"],"award-info":[{"award-number":["MIS Code 5047285"]}]},{"DOI":"10.13039\/100015230","name":"Fondation Cancer luxembourg","doi-asserted-by":"publisher","award":["FC\/2017\/05\/2MAP"],"award-info":[{"award-number":["FC\/2017\/05\/2MAP"]}],"id":[{"id":"10.13039\/100015230","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FC\/2017\/05\/2MAP"],"award-info":[{"award-number":["FC\/2017\/05\/2MAP"]}],"id":[{"id":"https:\/\/ror.org\/009yhf078","id-type":"ROR","asserted-by":"publisher"}]},{"name":"BIOMAGING-GR-DUTH","award":["MIS5002755"],"award-info":[{"award-number":["MIS5002755"]}]},{"name":"DEMOCRITUS UNIVERSITY OF THRACE"},{"id":[{"id":"https:\/\/ror.org\/03bfqnx40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chromosomal instability (CIN) arising from mitotic errors is a hallmark of cancer progression, yet how specific spindle assembly factors are co-opted to support aggressive tumor phenotypes remains incompletely understood. Hepatoma Upregulated Protein (HURP\/DLGAP5), a Ran-regulated microtubule-associated protein essential for kinetochore fiber stabilization and chromosome congression, is frequently overexpressed in aggressive cancers. Here, we investigated HURP\u2019s role across a breast cancer metastatic gradient\u2014immortalized MCF10A, the low-metastatic luminal T47D, and the highly metastatic triple-negative MDA-MB-231 cell lines\u2014integrating quantitative spindle analysis, kinetochore tension measurements, spindle checkpoint profiling, migration dynamics, and three-dimensional spheroid modeling. We show that total HURP protein levels increase with metastatic potential, yet spindle-bound HURP is paradoxically reduced in MDA-MB-231 cells, indicating cytoplasmic mislocalization despite increased total protein levels. HURP silencing induced cell-line-specific defects: moderate disorganization and misorientation in MCF10A and T47D cells, but catastrophic spindle collapse, apoptosis, and G2\/M arrest in MDA-MB-231 cells. Mechanistically, HURP depletion disrupted the spindle-associated levels and distributions of TPX2, Aurora-A, and NuMA in a subtype-dependent manner, implicating HURP as a context-dependent stabilizer of this mitotic regulatory axis. HURP loss reduced interkinetochore tension in all cell lines, but only MCF10A and T47D cells mounted a proportional BubR1-dependent checkpoint response; MDA-MB-231 cells showed reduced checkpoint signaling, consistent with constitutive spindle assembly checkpoint (SAC) attenuation in triple-negative breast cancer. Beyond mitosis, HURP depletion impaired collective migration and converted MDA-MB-231 cells from super-diffusive, amoeboid-like motility to sub-diffusive behavior, while minimally affecting the less aggressive cell lines. HURP-depleted MDA-MB-231 spheroids were significantly larger, less compact, and less spherical than controls, linking spindle regulation to tissue-level architectural coherence. These findings establish HURP as a multifunctional regulator coordinating mitotic fidelity, migration plasticity, and tumor architecture in breast cancer, with a selective dependency in highly metastatic cells, positioning it as a promising therapeutic target for aggressive breast cancers.<\/jats:p>","DOI":"10.3390\/ijms27135897","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"5897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HURP Silencing Differentially Impacts Spindle Architecture and Metastatic Behavior in Breast Cancer Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-0423","authenticated-orcid":false,"given":"Christos","family":"Efstathiou","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5932-9626","authenticated-orcid":false,"given":"Stylianos","family":"Didaskalou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lito","family":"Karkaletsou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2988-4823","authenticated-orcid":false,"given":"Stella","family":"Malichetoudi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenios","family":"Eftalitsidis","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Girod","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2255-3426","authenticated-orcid":false,"given":"Maria","family":"Koffa","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"524","article-title":"Breast Cancer Statistics, 2022","volume":"72","author":"Giaquinto","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1091\/mbc.6.12.1619","article-title":"Force generation by microtubule assembly\/disassembly in mitosis and related movements","volume":"6","author":"Inoue","year":"1995","journal-title":"Mol. Biol. Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41580-023-00584-0","article-title":"Mechanisms underlying spindle assembly and robustness","volume":"24","author":"Valdez","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/nature01599","article-title":"Cell division","volume":"422","author":"Scholey","year":"2003","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cub.2006.03.056","article-title":"HURP is part of a Ran-dependent complex involved in spindle formation","volume":"16","author":"Koffa","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/j.jmb.2006.10.064","article-title":"HURP wraps microtubule ends with an additional tubulin sheet that has a novel conformation of tubulin","volume":"365","author":"Santarella","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1083\/jcb.200511132","article-title":"HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture","volume":"173","author":"Wong","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/sj.onc.1206129","article-title":"Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma","volume":"22","author":"Tsou","year":"2003","journal-title":"Oncogene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.3892\/ol.2014.2614","article-title":"Hepatoma upregulated protein expression is involved in the pathogenesis of human breast carcinogenesis","volume":"8","author":"Chen","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_12","first-page":"4053","article-title":"Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer","volume":"19","author":"Xu","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Espinoza, I., Sakiyama, M.J., Ma, T., Fair, L., Zhou, X., Hassan, M., Zabaleta, J., and Gomez, C.R. (2016). Hypoxia on the Expression of Hepatoma Upregulated Protein in Prostate Cancer Cells. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00144"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3892\/ol.2022.13381","article-title":"MicroRNA-409-5p inhibits cell proliferation, and induces G(2)\/M phase arrest and apoptosis by targeting DLGAP5 in ovarian cancer cells","volume":"24","author":"Li","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s00384-019-03339-6","article-title":"Prognostic value of DLGAP5 in colorectal cancer","volume":"34","author":"Branchi","year":"2019","journal-title":"Int. J. Color. Dis."},{"key":"ref_16","first-page":"1682","article-title":"Prognostic and predictive value of HURP in non--small cell lung cancer","volume":"39","author":"Wang","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1007\/s12032-013-0804-4","article-title":"Evaluation of urinary HURP mRNA as a marker for detection of bladder cancer: Relation to bilharziasis","volume":"31","author":"Eissa","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Didaskalou, S., Efstathiou, C., Galtsidis, S., Kesisova, I., Halavatyi, A., Elmali, T., Tsolou, A., Girod, A., and Koffa, M. (2023). HURP localization in metaphase is the result of a multi-step process requiring its phosphorylation at Ser627 residue. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.981425"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garrido, G., and Vernos, I. (2016). Non-centrosomal TPX2-Dependent Regulation of the Aurora A Kinase: Functional Implications for Healthy and Pathological Cell Division. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00088"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S1097-2765(03)00392-7","article-title":"Structural basis of Aurora-A activation by TPX2 at the mitotic spindle","volume":"12","author":"Bayliss","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/ncb870","article-title":"Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells","volume":"4","author":"Gruss","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1083\/jcb.200204155","article-title":"Human TPX2 is required for targeting Aurora-A kinase to the spindle","volume":"158","author":"Kufer","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9689","DOI":"10.1038\/s41467-024-53630-6","article-title":"HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2","volume":"15","author":"Valdez","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1128\/MCB.01062-08","article-title":"Aurora-A kinase is essential for bipolar spindle formation and early development","volume":"29","author":"Cowley","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cub.2015.12.051","article-title":"NuMA Phosphorylation by Aurora-A Orchestrates Spindle Orientation","volume":"26","author":"Gallini","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/ncb1201-1069","article-title":"A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization","volume":"3","author":"Du","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1083\/jcb.201203166","article-title":"Cortical dynein is critical for proper spindle positioning in human cells","volume":"199","author":"Kotak","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1242\/jcs.115.9.1815","article-title":"Direct binding of NuMA to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules","volume":"115","author":"Haren","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/ncb2440","article-title":"Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation","volume":"14","author":"Kiyomitsu","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.cub.2020.10.096","article-title":"The Aurora-A\/TPX2 Axis Directs Spindle Orientation in Adherent Human Cells by Regulating NuMA and Microtubule Stability","volume":"31","author":"Polverino","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1242\/jcs.081406","article-title":"Mitotic spindle misorientation in cancer--out of alignment and into the fire","volume":"124","author":"Pease","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"317","DOI":"10.15252\/embr.201541143","article-title":"Chromosome misalignments induce spindle-positioning defects","volume":"17","author":"Tame","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qu, Y., Han, B., Yu, Y., Yao, W., Bose, S., Karlan, B.Y., Giuliano, A.E., and Cui, X. (2015). Evaluation of MCF10A as a Reliable Model for Normal Human Mammary Epithelial Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131285"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ijc.11172","article-title":"Breast cell invasive potential relates to the myoepithelial phenotype","volume":"106","author":"Gordon","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.bbrc.2017.03.114","article-title":"The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer","volume":"486","author":"Yu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.7150\/jca.18457","article-title":"Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping","volume":"8","author":"Dai","year":"2017","journal-title":"J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e202106170","DOI":"10.1083\/jcb.202106170","article-title":"Volumetric morphometry reveals spindle width as the best predictor of mammalian spindle scaling","volume":"221","author":"Kletter","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R1002","DOI":"10.1016\/j.cub.2015.08.051","article-title":"The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics","volume":"25","author":"Musacchio","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19108","DOI":"10.1073\/pnas.0904343106","article-title":"Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells","volume":"106","author":"Janssen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ccr.2008.07.002","article-title":"Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs","volume":"14","author":"Gascoigne","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cub.2006.04.043","article-title":"Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint","volume":"16","author":"Brito","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrm2720","article-title":"Collective cell migration in morphogenesis, regeneration and cancer","volume":"10","author":"Friedl","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ncb2548","article-title":"Classifying collective cancer cell invasion","volume":"14","author":"Friedl","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9237","DOI":"10.1038\/s41598-017-09300-3","article-title":"Amoeboid-mesenchymal migration plasticity promotes invasion only in complex heterogeneous microenvironments","volume":"7","author":"Talkenberger","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13008-015-0009-7","article-title":"Aneuploidy and chromosomal instability in cancer: A jackpot to chaos","volume":"10","author":"Giam","year":"2015","journal-title":"Cell Div."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.cell.2018.08.027","article-title":"The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment","volume":"174","author":"Bakhoum","year":"2018","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"R148","DOI":"10.1016\/j.cub.2014.01.019","article-title":"The mitotic origin of chromosomal instability","volume":"24","author":"Bakhoum","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_48","first-page":"230","article-title":"The Aurora-A\/TPX2 complex: A novel oncogenic holoenzyme?","volume":"1806","author":"Asteriti","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/sj.emboj.7601599","article-title":"Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner","volume":"26","author":"Toyoshima","year":"2007","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nmeth.1237","article-title":"Robust single-particle tracking in live-cell time-lapse sequences","volume":"5","author":"Jaqaman","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1093\/bioinformatics\/btx180","article-title":"Trainable Weka Segmentation: A machine learning tool for microscopy pixel classification","volume":"33","author":"Kaynig","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/s41592-022-01507-1","article-title":"TrackMate 7: Integrating state-of-the-art segmentation algorithms into tracking pipelines","volume":"19","author":"Ershov","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","article-title":"TrackMate: An open and extensible platform for single-particle tracking","volume":"115","author":"Tinevez","year":"2017","journal-title":"Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1038\/s41467-018-06563-w","article-title":"Levy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo","volume":"9","author":"Huda","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Takagi, H., Sato, M.J., Yanagida, T., and Ueda, M. (2008). Functional analysis of spontaneous cell movement under different physiological conditions. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002648"},{"key":"ref_56","unstructured":"Christian Tischer, R.P. (2026, June 07). CATS: Fiji Plugin for Context Aware Trainable Segmentation for Big Image Data, 2019. Available online: https:\/\/zenodo.org\/records\/2600293."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5897\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:51:41Z","timestamp":1782867101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":56,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135897"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135897","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}