Three-dimensional Culture and Clinical Drug Responses of a Highly Metastatic Human Ovarian Cancer HO-8910PM Cells in Nanofibrous Microenvironments of Three Hydrogel Biomaterials
Open accessAbstract
Abstract Background Ovarian cancer is a highly aggressive malignant disease in gynecologic cancer. It is an urgent task to develop three-dimensional (3D) cell models in vitro and dissect the cell progression-related drug resistance mechanisms in vivo. In the present study, RADA16-I peptide has the reticulated nanofiber scaffold networks in hydrogel, which is utilized to develop robust 3D cell culture of a high metastatic human ovarian cancer HO-8910PM cell line accompanied with the counterparts of Matrigel and collagen I. Results Consequently, HO-8910PM cells were successfully cultivated in three types of hydrogel biomaterials, such as RADA16-I hydrogel, Matrigel, and collagen I, according to 3D cell culture protocols. Designer RADA16-I peptide had well-defined nanofiber networks architecture in hydrogel, which provided nanofiber cell microenvironments analogous to Matrigel and collagen I. 3D-cultured HO-8910PM cells in RADA16-I hydrogel, Matrigel, and collagen I showed viable cell proliferation, proper cell growth, and diverse cell shapes in morphology at the desired time points. For a long 3D cell culture period, HO-8910PM cells showed distinct cell aggregate growth patterns in RADA16-I hydrogel, Matrigel, and collagen I, such as cell aggregates, cell colonies, cell clusters, cell strips, and multicellular tumor spheroids (MCTS). The cell distribution and alignment were described vigorously. Moreover, the molecular expression of integrin β1, E-cadherin and N-cadherin were quantitatively analyzed in 3D-cultured MCTS of HO-8910PM cells by immunohistochemistry and western blotting assays. The chemosensitivity assay for clinical drug responses in 3D context indicated that HO-8910PM cells in three types of hydrogels showed significantly higher chemoresistance to cisplatin and paclitaxel compared to 2D flat cell culture, including IC 50 values and inhibition rates. Conclusion Based on these results, RADA16-I hydrogel is a highly competent, high-profile, and proactive nanofiber scaffold to maintain viable cell proliferation and high cell vitality in 3D cell models, which may be particularly utilized to develop useful clinical drug screening platform in vitro.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A disadvantage of some peptide-based hydrogels is their low mechanical strength, where hydrogels with encapsulated cells are able to be disrupted easily by mechanical forces such as pipetting.
“A disadvantage of some peptide-based hydrogels is their low mechanical strength, where hydrogels with encapsulated cells are able to be disrupted easily by mechanical forces such as pipetting (Song et al., 2020).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Song et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer
Bowtell, D. D. L., Böhm, S., Ahmed, A. A., Aspuria, P.-J. P., Bast, R. C., Beral, V., Berek, J. S., Birrer, M. J., Blagden, S. P., Bookman, M. A., et al. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4019 · Cited by 1,365 · see citing works
Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Labernadie, A., Kato, T., Brugués, A., Serra‐Picamal, X., Derzsi, S., Arwert, E. N., Weston, A., González-Tarragó, V., Elósegui-Artola, A., Albertazzi, L., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3478 · Cited by 747 · see citing works
Dynamic reassembly of peptide RADA16 nanofiber scaffold
Yokoi, H., Kinoshita, T., & Zhang, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407843102 · Cited by 681 · see citing works
Self-complementary oligopeptide matrices support mammalian cell attachment
Zhang, S., Holmes, T. C., DiPersio, C. M., Hynes, R. O., Su, X., & Rich, A. (1995) · Biomaterials · doi:10.1016/0142-9612(95)96874-y · Cited by 679 · see citing works
Gelain, F., Bottai, D., Vescovi, A., & Zhang, S. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000119 · Cited by 612 · see citing works
Antoine, E. E., Vlachos, P. P., & Rylander, M. N. (2014) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2014.0086 · Cited by 611 · see citing works
McCluggage, W. G. (2011) · Pathology · doi:10.1097/pat.0b013e328348a6e7 · Cited by 499 · see citing works
Matrigel: From discovery and ECM mimicry to assays and models for cancer research
Benton, G., Arnaoutova, I., George, J., Kleinman, H. K., & Koblinski, J. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.005 · Cited by 477 · see citing works
Designer self-assembling peptide nanofiber biological materials
Hauser, C. A. E., & Zhang, S. (2010) · Chemical Society Reviews · doi:10.1039/b921448h · Cited by 371 · see citing works
Integrins and cadherins join forces to form adhesive networks
Weber, G. F., Bjerke, M. A., & DeSimone, D. W. (2011) · Journal of Cell Science · doi:10.1242/jcs.064618 · Cited by 345 · see citing works
3D in vitro bioengineered tumors based on collagen I hydrogels
Szot, C. S., Buchanan, C. F., Freeman, J. W., & Rylander, M. N. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.07.001 · Cited by 304 · see citing works
Lee, J. M., Mhawech-Fauceglia, P. Y., Lee, N., Parsanian, L. C., Lin, Y. G., Gayther, S. A., & Lawrenson, K. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.41 · Cited by 302 · see citing works
Koutsopoulos, S., & Zhang, S. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2012.09.010 · Cited by 181 · see citing works
Three-Dimensional Primary Hepatocyte Culture in Synthetic Self-Assembling Peptide Hydrogel
Wang, S., Nagrath, D., Chen, P. C., Francois Berthiaume, B., & Yarmush, M. L. (2008) · Tissue Engineering Part A · doi:10.1089/tea.2007.0143 · Cited by 167 · see citing works
Peptide Hydrogels – Versatile Matrices for 3D Cell Culture in Cancer Medicine
Worthington, P., Pochan, D. J., & Langhans, S. A. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00092 · Cited by 166 · see citing works
Garreta, E., Genové, E., Borrós, S., & Semino, C. E. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.2215 · Cited by 158 · see citing works
Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers
Cormier, A. R., Pang, X., Zimmerman, M. I., Zhou, H., & Paravastu, A. K. (2013) · ACS Nano · doi:10.1021/nn401562f · Cited by 155 · see citing works
A versatile 3D tissue matrix scaffold system for tumor modeling and drug screening
Rijal, G., & Li, W. (2017) · Science Advances · doi:10.1126/sciadv.1700764 · Cited by 154 · see citing works
Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment
Herrmann, D., Conway, J. R. W., Vennin, C., Magenau, A., Hughes, W. E., Morton, J. P., & Timpson, P. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu108 · Cited by 141 · see citing works
Peptide Hydrogelation and Cell Encapsulation for 3D Culture of MCF-7 Breast Cancer Cells
Huang, H., Ding, Y., Sun, X. S., & Nguyen, T. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059482 · Cited by 138 · see citing works
Raghavan, S. A., Ward, M. R., Rowley, K. R., Wold, R. M., Takayama, S., Buckanovich, R. J., & Mehta, G. (2015) · Gynecologic Oncology · doi:10.1016/j.ygyno.2015.04.014 · Cited by 136 · see citing works
Peptidic Biomaterials: From Self-Assembling to Regenerative Medicine
Pugliese, R., & Gelain, F. (2017) · Trends in Biotechnology · doi:10.1016/j.tibtech.2016.09.004 · Cited by 133 · see citing works
Rubiano, A. M., Delitto, D., Han, S., Gerber, M. H., Galitz, C., Trevino, J. G., Thomas, R. M., Hughes, S. J., & Simmons, C. S. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.11.037 · Cited by 132 · see citing works
Liu, J. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s24038 · Cited by 128 · see citing works
Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments
Antoine, E. E., Vlachos, P. P., & Rylander, M. N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0122500 · Cited by 125 · see citing works
N-cadherin-mediated cell–cell adhesion promotes cell migration in a three-dimensional matrix
Shih, W., & Yamada, S. (2012) · Journal of Cell Science · doi:10.1242/jcs.103861 · Cited by 123 · see citing works
Yang, Z., Xu, H., & Zhao, X. (2020) · Advanced Science · doi:10.1002/advs.201903718 · Cited by 120 · see citing works
Self-citationCigognini, D., Satta, A., Colleoni, B., Silva, D. A. S., Donegà, M., Antonini, S., & Gelain, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019782 · Cited by 116 · see citing works
Rosso, M., Majem, B., Devis, L., Lapyckyj, L., Besso, M. J., Llauradó, M., Abascal, M. F., Matos, M. L., Lanau, L., Castellví, J., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184439 · Cited by 102 · see citing works
Marchini, A., Raspa, A., Pugliese, R., El Malek, M. A., Pastori, V., Lecchi, M., Vescovi, A. L., & Gelain, F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818392116 · Cited by 99 · see citing works
Yang, Z., & Zhao, X. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s15279 · Cited by 96 · see citing works
Self-citationBiomimetic tumor microenvironments based on collagen matrices
Sapudom, J., & Pompe, W. (2018) · Biomaterials Science · doi:10.1039/c8bm00303c · Cited by 91 · see citing works
Hamada, K., Hirose, M., Yamashita, T., et al. (2007) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31439 · Cited by 88 · see citing works
Chen, W., Li, Q., Cao, J., Li, P., Li, J., Zhang, J., Luo, S., & Yu, H. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.10.024 · Cited by 84 · see citing works
Klymenko, Y., Kim, O., Loughran, E. A., Yang, J., Lombard, R., Alber, M., & Stack, M. S. (2017) · Oncogene · doi:10.1038/onc.2017.171 · Cited by 84 · see citing works
Microfluidics for studying metastatic patterns of lung cancer
Ruzycka-Ayoush, M., Cimpan, M. R., Ríos-Mondragón, I., & Grudziński, I. P. (2019) · Journal of Nanobiotechnology · doi:10.1186/s12951-019-0492-0 · Cited by 82 · see citing works
Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges
Montanez-Sauri, S. I., Beebe, D. J., & Sung, K. E. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1738-5 · Cited by 79 · see citing works
Self-Assembling Peptides as Extracellular Matrix Mimics to Influence Stem Cell's Fate
Hellmund, K. S., & Koksch, B. (2019) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00172 · Cited by 77 · see citing works
Dangi-Garimella, S. Y., Sahai, V., Ebine, K., Kumar, K., & Munshi, H. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064566 · Cited by 75 · see citing works
Tasdemir, N., Bossart, E. A., Li, Z., Zhu, L., Sikora, M. J., Levine, K. M., Jacobsen, B. M., Tseng, G. C., Davidson, N. E., & Oesterreich, S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1416 · Cited by 71 · see citing works
Edmondson, R., Adcock, A. F., & Yang, L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158116 · Cited by 69 · see citing works
Fontana, F., Raimondi, M., Marzagalli, M., et al. (2019) · Cells · doi:10.3390/cells8020143 · Cited by 62 · see citing works
Shen-hua, X., Lijuan, Q., Hanzhou, N., et al. (1999) · PubMed · Cited by 61 · see citing works
Mi, K., Wang, G., Liu, Z., Feng, Z., Huang, B. S., & Zhao, X. (2009) · Macromolecular Bioscience · doi:10.1002/mabi.200800262 · Cited by 60 · see citing works
Klymenko, Y., Johnson, J. K., Bos, B., Lombard, R., Campbell, L., Loughran, E. A., & Stack, M. S. (2017) · Neoplasia · doi:10.1016/j.neo.2017.04.002 · Cited by 59 · see citing works
Brasch, J., Katsamba, P. S., Harrison, O. J., Ahlsén, G., Troyanovsky, R. B., Indra, I., Kaczynska, A., Kaeser, B., Troyanovsky, S. M., Honig, B. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.012 · Cited by 59 · see citing works
Negah, S. S., Oliazadeh, P., Jahan‐Abad, A. J., Eshaghabadi, A., Samini, F., Ghasemi, S., Asghari, A., & Gorji, A. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.05.010 · Cited by 57 · see citing works
Ashworth, J., Thompson, J. L., James, J. R., Slater, C. E., Pijuan‐Galito, S., Lis-Slimak, K., Holley, R. J., Meade, K. A., Thompson, A., Arkill, K. P., et al. (2019) · Matrix Biology · doi:10.1016/j.matbio.2019.06.009 · Cited by 56 · see citing works
Self‐Assembling Peptide Gels for 3D Prostate Cancer Spheroid Culture
Hainline, K. M., Gu, F., Handley, J., Tian, Y. F., Wu, Y., de Wet, L., Griend, D. J. V., & Collier, J. H. (2018) · Macromolecular Bioscience · doi:10.1002/mabi.201800249 · Cited by 55 · see citing works
Molecular Mechanisms of RADA16-1 Peptide on Fast Stop Bleeding in Rat Models
Wang, T., Zhong, X., Wang, S., Lv, F., & Zhao, X. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131115279 · Cited by 54 · see citing works
Weiswald, L., Richon, S., Massonnet, G., Jm, G., Vacher, S., Laurendeau, I., Cottu, P. H., Marangoni, E., Némati, F., Validire, P., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.132 · Cited by 54 · see citing works
Design of novel 2D and 3D biointerfaces using self-organization to control cell behavior
Tanaka, M. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2010.10.002 · Cited by 52 · see citing works
Systematic Studies of a Self-Assembling Peptide Nanofiber Scaffold with Other Scaffolds
Gelain, F., Lomander, A., Vescovi, A. L., et al. (2006) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2007.154 · Cited by 50 · see citing works
Xu, S., Yang, Y., Dong, L., Qiu, W., Yang, L., Wang, X., & Liu, L. (2014) · Scientific Reports · doi:10.1038/srep05646 · Cited by 50 · see citing works
A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns
Loessner, D., Rockstroh, A., Shokoohmand, A., Holzapfel, B. M., Wagner, F., Baldwin, J., Boxberg, M., Schmalfeldt, B., Lengyel, E. R., Clements, J. A., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.10.014 · Cited by 50 · see citing works
Nii, T., Makino, K., & Tabata, Y. (2019) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2019.0189 · Cited by 47 · see citing works
Matte, I., Legault, C. M., Garde‐Granger, P., Laplante, C., Bessette, P., Rancourt, C., & Piché, A. (2016) · Clinical & Experimental Metastasis · doi:10.1007/s10585-016-9821-y · Cited by 44 · see citing works
Three-dimensional modeling of ovarian cancer
White, E. A., Kenny, H. A., & Lengyel, E. R. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.07.003 · Cited by 42 · see citing works
Jung, P.-S., Kim, D., Kim, M.-B., et al. (2013) · PubMed · Cited by 41 · see citing works
Nakahara, H., Misawa, H., Yoshida, A., et al. (2010) · Cell Transplantation · doi:10.3727/096368910x508906 · Cited by 38 · see citing works
Sun, Y., Zhang, Y., Tian, L., et al. (2016) · Biomedical Materials · doi:10.1088/1748-605x/12/1/015007 · Cited by 34 · see citing works
Design Parameters of Tissue‐Engineering Scaffolds at the Atomic Scale
Jekhmane, S., Prachař, M., Pugliese, R., Fontana, F., Medeiros‐Silva, J., Gelain, F., & Weingarth, M. H. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201907880 · Cited by 34 · see citing works
Choi, P., Yang, J., Ng, S., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6588 · Cited by 33 · see citing works
Tang, C., Shao, X., Sun, B., et al. (2009) · International Journal of Molecular Sciences · doi:10.3390/ijms10052136 · Cited by 32 · see citing works
Çimenci, Ç. E., Kurtulus, G. U., Çalışkan, Ö. Ş., Guler, M. O., & Tekinay, A. B. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00514 · Cited by 32 · see citing works
Mi, K., & Xing, Z. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s66723 · Cited by 30 · see citing works
Lin, C., & Korc, M. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.008 · Cited by 28 · see citing works
Techniques for assessing 3-D cell–matrix mechanical interactions in vitro and in vivo
Miron-Mendoza, M., Koppaka, V., Zhou, C., & Petroll, W. M. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.06.018 · Cited by 25 · see citing works
Hydrophobic Patterning‐Based 3D Microfluidic Cell Culture Assay
Han, S., Kim, J.-H., Li, R., Ma, A. L., Kwan, V. W.-S., Luong, K., & Sohn, L. L. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201800122 · Cited by 24 · see citing works
Gambara, G., Gaebler, M., Keilholz, U., Regenbrecht, C. R. A., & Silvestri, A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00077 · Cited by 22 · see citing works
Lee, S., Kim, Y., Kim, M.-B., et al. (2012) · PubMed · doi:10.18926/amo/48567 · Cited by 17 · see citing works
Hypoxia promotes HO-8910PM ovarian cancer cell invasion via Snail-mediated MT1-MMP upregulation
Sun, L., Lin, P., Qin, Z., Liu, Y., Deng, L., & Lu, C. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215570205 · Cited by 16 · see citing works
Song, H., Han, Y.-Z., Cai, G.-H., Tang, F., Yang, Z., Ao, D.-S., & Zhou, A. (2015) · PubMed · Cited by 12 · see citing works
Self-citation3D Cell Culture in a Self-Assembled Nanofiber Environment
Chai, Y. W., Lee, E. H., Gubbe, J. D., & Brekke, J. H. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162853 · Cited by 11 · see citing works
Yang, Z., Zhuang, H., Song, H., et al. (2017) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2018.14384 · Cited by 8 · see citing works
Self-citationWeber, R. J., & McCullagh, M. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c00048 · Cited by 4 · see citing works
Nanometric self-assembling peptide layers maintain adult hepatocyte phenotype in sandwich cultures
Wu, J., Marí‐Buyé, N., Fernández-Muiños, T., Borrós, S., Favia, P., & Semino, C. E. (2010) · Journal of Nanobiotechnology · doi:10.1186/1477-3155-8-29 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Yee, C., Dickson, K.-A., Muntasir, M. N., Ma, Y., & Marsh, D. J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.836984 · Cited by 66 · see citing works
- Authors
- Song, H., Cai, G.-H., Liang, J., Ao, D.-S., Wang, H., & Yang, Z.-H.
- Affiliations
- Zunyi Medical University (CN)
- Venue
- Journal of Nanobiotechnology
- Published
- 2020-06-11
- Volume
- 18
- Issue
- 1
- Pages
- 90-90
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC7291456
- OpenAlex
- W3034753503
- Cited by
- 52
- References
- 78
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 5 · 2022: 14 · 2021: 12 · 2020: 2
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81160290, 81660340)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- ovarian cancer, HO-8910PM cells, nanofibrous hydrogels, 3D cell culture, tumor spheroids, chemoresistance, cisplatin, paclitaxel, Matrigel, type I collagen, beta1 integrin, E-cadherin, N-cadherin, cell alignment, drug screening
- MeSH terms
- Antineoplastic Agents, Biocompatible Materials, Female, Humans, Ovarian Neoplasms, Cell Culture Techniques, Hydrogels, Cell Line, Tumor, Cell Proliferation, Nanofibers, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review