Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota
Open accessAbstract
Parathyroid hormone (PTH) is a critical regulator of skeletal development that promotes both bone formation and bone resorption. Using microbiota depletion by wide-spectrum antibiotics and germ-free (GF) female mice, we showed that the microbiota was required for PTH to stimulate bone formation and increase bone mass. Microbiota depletion lowered butyrate levels, a metabolite responsible for gut-bone communication, while reestablishment of physiologic levels of butyrate restored PTH-induced anabolism. The permissive activity of butyrate was mediated by GPR43 signaling in dendritic cells and by GPR43-independent signaling in T cells. Butyrate was required for PTH to increase the number of bone marrow (BM) regulatory T cells (Tregs). Tregs stimulated production of the osteogenic Wnt ligand Wnt10b by BM CD8+ T cells, which activated Wnt-dependent bone formation. Together, these data highlight the role that butyrate produced by gut luminal microbiota plays in triggering regulatory pathways, which are critical for the anabolic action of PTH in bone.
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?
The bone-forming effect of intermittent PTH signaling closely depends on short-chain fatty acids-specifically butyrate.
“Finally, it is understood that the bone-forming effect of intermittent PTH signaling closely depends on SCFAs—specifically, butyrate, a product of the GM.”
From Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics (2023) · cites this paper as [33]
The Discussion reports that gut-microbiota-derived butyrate was required for intermittent PTH to induce bone anabolism in young female mice. The citing sentence states the dependence without that population limit; the paper says whether the mechanism is sex dependent remains unknown. (LLM, conf=0.80)
Experimental — accuracy not yet measuredDifferentiated Treg cells stimulate the Wnt pathway, which is pivotal for bone formation and osteoblast differentiation.
“Differentiated Treg cells then stimulate the Wnt pathway, which is pivotal for bone formation and osteoblast differentiation, as discussed above [15,33].”
From Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics (2023) · cites this paper as [33]
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
Dendritic cells and the control of immunity
Banchereau, J., & Steinman, R. M. (1998) · Nature · doi:10.1038/32588 · Cited by 14,244 · see citing works
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838 · see citing works
Guidelines for assessment of bone microstructure in rodents using micro–computed tomography
Bouxsein, M., Boyd, S. K., Christiansen, B., Guldberg, R. E., Jepsen, K. J., & Müller, R. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.141 · Cited by 4,461 · see citing works
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241 · see citing works
Dempster, D. W., Compston, J. E., Drezner, M. K., Glorieux, F. H., Kanis, J. A., Malluche, H., Meunier, P. J., Ott, S. M., Recker, R. R., & Parfitt, A. M. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1805 · Cited by 2,543 · see citing works
Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.007 · Cited by 2,368 · see citing works
Mechanisms of Foxp3+ T Regulatory Cell-Mediated Suppression
Shevach, E. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.010 · Cited by 1,754 · see citing works
Setoguchi, R., Hori, S., Takahashi, T., & Sakaguchi, S. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041982 · Cited by 1,234 · see citing works
The gut microbiota regulates bone mass in mice
Sjögren, K., Engdahl, C., Henning, P., Lerner, U. H., Tremaroli, V., Lagerquist, M. K., Bäckhed, F., & Ohlsson, C. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1588 · Cited by 822 · see citing works
Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss
Lucas, S., Omata, Y., Hofmann, J., Böttcher, M., Iljazovic, A., Sarter, K., Albrecht, O., Schulz, O., Krishnacoumar, B., Krönke, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02490-4 · Cited by 815 · see citing works
Gut microbiota induce IGF-1 and promote bone formation and growth
Yan, J., Herzog, J. W., Tsang, K., Brennan, C. A., Bower, M. A., Garrett, W. S., Sartor, B. R., Aliprantis, A. O., & Charles, J. F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607235113 · Cited by 750 · see citing works
Molecular and cellular mechanisms of the anabolic effect of intermittent PTH
Jilka, R. L. (2007) · Bone · doi:10.1016/j.bone.2007.03.017 · Cited by 722 · see citing works
Bellido, T., Ali, A., Gubrij, I. B., Plotkin, L. I., Fu, Q., O’Brien, C. A., Manolagas, S. C., & Jilka, R. L. (2005) · Endocrinology · doi:10.1210/en.2005-0239 · Cited by 640 · see citing works
SOST is a target gene for PTH in bone
Keller, H., & Kneissel, M. (2005) · Bone · doi:10.1016/j.bone.2005.03.018 · Cited by 618 · see citing works
Tyagi, A. M., Yu, M., Darby, T. M., Vaccaro, C., Li, J., Owens, J. A., Hsu, E., Adams, J., Weitzmann, M. N., Jones, R. M., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.10.013 · Cited by 575 · see citing works
Self-citationIn vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche
Fujisaki, J., Wu, J. W., Carlson, A. L., Silberstein, L., Putheti, P., Larocca, R. A., Gao, W., Saito, T. I., Celso, C. L., Tsuyuzaki, H., et al. (2011) · Nature · doi:10.1038/nature10160 · Cited by 570 · see citing works
Development and maintenance of intestinal regulatory T cells
Tanoue, T., Atarashi, K., & Honda, K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.36 · Cited by 553 · see citing works
Nilsson, N. E., Kotarsky, K., Owman, C., & Olde, B. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00488-1 · Cited by 540 · see citing works
The gut-bone axis: How bacterial metabolites bridge the distance
Zaiss, M. M., Jones, R. M., Schett, G., & Pacifici, R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128521 · Cited by 403 · see citing works
Self-citationTreg cells suppress osteoclast formation: a new link between the immune system and bone.
Zaiss, M., Axmann, R., Zwerina, J., Polzer, K., Gückel, E., Skapenko, A., Schulze-Koops, H., Horwood, N., Cope, A., & Schett, G. (2007) · Arthritis & Rheumatism · doi:10.1002/art.23138 · Cited by 397 · see citing works
BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2
Cario, E. (2005) · Gut · doi:10.1136/gut.2004.062794 · Cited by 350 · see citing works
McCarthy, T. L., & CANALIS, E. M. (1989) · Endocrinology · doi:10.1210/endo-124-3-1247 · Cited by 336 · see citing works
Bilezikian, J. P. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01225 · Cited by 326 · see citing works
Metabolic control of regulatory T cell development and function
Zeng, H., & Chi, H. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.08.003 · Cited by 275 · see citing works
Liu, Y., Yang, R., Liu, X., Zhou, Y., Qu, C., Kikuiri, T., Wang, S., Zandi, E., Du, J., Ambudkar, I. S., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.03.005 · Cited by 271 · see citing works
Interferon-λ orchestrates innate and adaptive mucosal immune responses
Ye, L., Schnepf, D., & Staeheli, P. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0182-z · Cited by 268 · see citing works
Parathyroid hormone: a double-edged sword for bone metabolism
Qin, L., Raggatt, L. J., & Partridge, N. C. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.01.006 · Cited by 264 · see citing works
Oursler, M. J., CORTESE, C., Keeting, P. E., Anderson, M. A., Bonde, S. K., Riggs, B. L., & Spelsberg, T. C. (1991) · Endocrinology · doi:10.1210/endo-129-6-3313 · Cited by 263 · see citing works
Bikle, D. D., Sakata, T., Leary, C., Elalieh, H. Z., Ginzinger, D. G., Rosen, C. J., Beamer, W. G., Majumdar, S., & Halloran, B. P. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.9.1570 · Cited by 259 · see citing works
Regulation of Bone Remodeling by Parathyroid HormonePreprint
Wein, M. N., & Kronenberg, H. M. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031237 · Cited by 243 · see citing works
Parathyroid hormone is essential for normal fetal bone formation
Miao, D., He, B., Karaplis, A. C., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14817 · Cited by 230 · see citing works
Guo, J., Liu, M., Yang, D., Bouxsein, M., Saito, H., Galvin, R. J. S., Kuhstoss, S. A., Thomas, C. C., Schipani, E., Baron, R., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.12.007 · Cited by 222 · see citing works
Hydrogen Sulfide Signaling in the Gastrointestinal Tract
Linden, D. R. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5312 · Cited by 222 · see citing works
Lefrançois, L., & Lycke, N. Y. (1996) · Current Protocols in Immunology · doi:10.1002/0471142735.im0319s17 · Cited by 207 · see citing works
Cutting Edge: TLR2 Directly Triggers Th1 Effector Functions
Imanishi, T., Hara, H., Suzuki, S., Suzuki, N., Akira, S., & Saito, T. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6715 · Cited by 200 · see citing works
T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling
Terauchi, M., Li, J., Bedi, B., Baek, K., Tawfeek, H. A. W., Galley, S. A., Gilbert, L. C., Nanes, M. S., Zayzafoon, M., Guldberg, R. E., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.07.010 · Cited by 194 · see citing works
Self-citationMicrobial regulation of host hydrogen sulfide bioavailability and metabolism
Shen, X., Carlström, M., Borniquel, S., Jädert, C., Kevil, C. G., & Lundberg, J. O. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.02.024 · Cited by 194 · see citing works
Lei, H., Schmidt‐Bleek, K., Dienelt, A., Reinke, P., & Volk, H. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00184 · Cited by 188 · see citing works
Knudsen, K. E. B. (2015) · Advances in Nutrition · doi:10.3945/an.114.007450 · Cited by 185 · see citing works
Kim, Y., Lee, C., Nah, S.-S., Mun, S. H., Yoo, B., & Moon, H. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.042 · Cited by 180 · see citing works
Annison, G., Illman, R. J., & Topping, D. L. (2003) · Journal of Nutrition · doi:10.1093/jn/133.11.3523 · Cited by 171 · see citing works
Saini, V., Marengi, D. A., Barry, K. J., Fulzele, K. S., Heiden, E., Liu, X., Dedic, C., Maeda, A., Lotinun, S., Baron, R., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.441360 · Cited by 167 · see citing works
Gene array analysis of Wnt-regulated genes in C3H10T1/2 cells
Jackson, A. M., Vayssière, B., Garcia, T., Newell, W., Baron, R., Roman‐Roman, S., & Rawadi, G. (2005) · Bone · doi:10.1016/j.bone.2005.01.007 · Cited by 166 · see citing works
Uzawa, T. (1995) · EMC - Cardiologie-Angéiologie · doi:10.1016/8756-3282(95)90194-9 · Cited by 163 · see citing works
Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis
Kelchtermans, H., Geboes, L., Mitera, T., Huskens, D., Leclercq, G., & Matthys, P. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.086066 · Cited by 160 · see citing works
Zaiss, M. M., Sarter, K., Hess, A., Engelke, K., Böhm, C., Nimmerjahn, F., Voll, R., Schett, G., & David, J. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27535 · Cited by 122 · see citing works
Novince, C. M., Whittow, C. R., Aartun, J. D., Hathaway, J. D., Poulides, N., Chavez, M. B., Steinkamp, H. M., Kirkwood, K. A., Huang, E., Westwater, C., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-06126-x · Cited by 121 · see citing works
Silvestrini, G., Ballanti, P., Leopizzi, M., Sebastiani, M., Berni, S., Vito, M. D., & BONUCCI, E. (2007) · Journal of Molecular Histology · doi:10.1007/s10735-007-9096-3 · Cited by 118 · see citing works
Delgado-Calle, J., Tu, X., Pacheco-Costa, R., McAndrews, K., Edwards, R., Pellegrini, G. G., Kuhlenschmidt, K., Olivos, N., Robling, A., Peacock, M., et al. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3011 · Cited by 114 · see citing works
Li, J., D’Amelio, P., Robinson, J. W., Walker, L. D., Vaccaro, C., Luo, T., Tyagi, A. M., Yu, M., Reott, M. A., Sassi, F., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.012 · Cited by 105 · see citing works
Self-citationBedi, B., Li, J., Tawfeek, H. A. W., Baek, K., Adams, J., Vangara, S. S., Chang, M.-K., Kneissel, M., Weitzmann, M. N., & Pacifici, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120735109 · Cited by 100 · see citing works
Self-citationLi, J., Walker, L. D., Tyagi, A. M., Adams, J., Weitzmann, M. N., & Pacifici, R. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2044 · Cited by 72 · see citing works
Self-citationYu, M., D’Amelio, P., Tyagi, A. M., Vaccaro, C., Li, J., Hsu, E., Buondonno, I., Sassi, F., Adams, J., Weitzmann, M. N., et al. (2017) · EMBO Reports · doi:10.15252/embr.201744421 · Cited by 69 · see citing works
Self-citationIida‐Klein, A., Lu, S. S., Kapadia, R. D., Burkhart, M., Moreno, A., Dempster, D. W., & Lindsay, R. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06270 · Cited by 61 · see citing works
Regulatory T cells as a potent target for controlling bone loss
Yuan, F., Li, X., Lü, W., Xu, R., Zhao, Y., Li, C.-W., Li, J., & Chen, F. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.09.120 · Cited by 58 · see citing works
Self-citationWu, Y., & Kumar, R. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.879 · Cited by 54 · see citing works
Jóhannesson, B., Sattler, S., Semenova, E., et al. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.015362 · Cited by 47 · see citing works
PTH expands short-term murine hemopoietic stem cells through T cells
Li, J., Adams, J., Calvi, L. M., et al. (2012) · Blood · doi:10.1182/blood-2012-06-438531 · Cited by 44 · see citing works
Self-citationT Cell–Expressed CD40L Potentiates the Bone Anabolic Activity of Intermittent PTH Treatment
Robinson, J. W., Li, J., Walker, L. D., Tyagi, A. M., Reott, M. A., Yu, M., Adams, J., Weitzmann, M. N., & Pacifici, R. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2394 · Cited by 35 · see citing works
Self-citationPark, H., Baek, K., Baek, J., & Kim, H. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24790 · Cited by 33 · see citing works
Anguela, X. M., Tafuro, S., Roca, C., Callejas, D., Agudo, J., Obach, M., Ribera, A., Ruzo, A., Mann, C. J., Casellas, A., et al. (2012) · Diabetes · doi:10.2337/db11-1776 · Cited by 31 · see citing works
Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients
D’Amelio, P., Sassi, F., Buondonno, I., Fornelli, G., Spertino, E., D’Amico, L., Marchetti, M., Lucchiari, M., Roato, I., & Isaia, G. (2015) · Osteoporosis International · doi:10.1007/s00198-015-3189-8 · Cited by 24 · see citing works
Huang, H., Chikazu, D., Voznesensky, O. S., et al. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091019 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Potts J. Chapter 13. In: Avioli LV, Krane S, eds. Metabolic Bone Diseases. San Diego, CA: Academ- ic Press; 1998:411-442.
- Qin L, Raggatt LJ, Partridge NC. Parathyroid hor- mone: a double-edged sword for bone metabo- lism. Trends Endocrinol Metab. 2004;15(2):60-65.
- Smith PM, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-573.
Cited by
Sorted by citations
Advances in pathogenesis and therapeutic strategies for osteoporosis
Song, S., Guo, Y., Yang, Y., & Fu, D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108168 · Cited by 476 · see citing works
Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis
Lyu, Z., Hu, Y., Guo, Y., & Liu, D. (2023) · Bone Research · doi:10.1038/s41413-023-00264-x · Cited by 207 · see citing works
Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics
Adejuyigbe, B., Kallini, J., Chiou, D., & Kallini, J. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914583 · Cited by 148 · see citing works
Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice
Dar, H. Y., Perrien, D. S., Pal, S., Stoica, A., Uppuganti, S., Nyman, J. S., Jones, R. M., Weitzmann, M. N., & Pacifici, R. (2023) · Journal of Clinical Investigation · doi:10.1172/jci166577 · Cited by 48 · see citing works
Self-citationT cells heal bone fractures with help from the gut microbiome
Aurora, R., & Silva, M. J. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167311 · Cited by 21 · see citing works
- Authors
- Li, J.-Y., Yu, M., Pal, S., Tyagi, A. M., Dar, H., Adams, J., Weitzmann, M. N., Jones, R. M., & Pacifici, R.
- Affiliations
- Emory University (US)
- Corresponding author
- Pacifici, Roberto
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2020-03-03
- Volume
- 130
- Issue
- 4
- Pages
- 1767-1781
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7108906
- OpenAlex
- W2999491357
- Cited by
- 198
- References
- 65
- Citations by year
- 2026: 45 · 2025: 24 · 2024: 31 · 2023: 28 · 2022: 28 · 2021: 29 · 2020: 13
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (DK112946, DK108842)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- parathyroid hormone, bone formation, butyrate, gut microbiota, gut-bone axis, GPR43, dendritic cells, regulatory T cells, Wnt10b, Wnt signaling, bone marrow, bone mass, germ-free mice, antibiotic depletion
- MeSH terms
- Gastrointestinal Microbiome, Animals, Butyrates, Osteogenesis, Parathyroid Hormone, Mice, Knockout, CD8-Positive T-Lymphocytes, Receptors, G-Protein-Coupled, T-Lymphocytes, Regulatory, Wnt Proteins, Mice
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
