{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:47:11Z","timestamp":1793490431065,"version":"4.5.0"},"reference-count":21,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Intramural Research Program of the National Center for Advancing Translational Sciences"},{"name":"The National Institute of Environmental Health Sciences\/Division of Translational Toxicology Program to the NCATS, National Institutes of Health","award":["IAA #NTR 12003"],"award-info":[{"award-number":["IAA #NTR 12003"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Botanical supplements are consumed to improve health despite the mystery of their mechanisms. One possible effect is hormesis, defined as a beneficial and stimulatory health effect at a low dose and detrimental effect at a high dose, or vice versa. Hormesis is usually discovered by manually examining the shape of dose-response curves, which is not scalable to the large number of chemical-assay combinations found in high-throughput screening (HTS) results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We proposed a semi-automatic statistical testing procedure to quickly evaluate large-scale dose-response data, accompanied by an R package\n                      <jats:italic toggle=\"yes\">shorm<\/jats:italic>\n                      for easy implementation. The nonparametric shape tests are more flexible with few assumptions. We also developed a new visualization method to represent the test conclusions and uncertainties simultaneously. This representation highlights both significant and ambiguous findings for efficient examination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We applied this method to a data set of 4860 chemical-assay pairs and identified 561 (12%) dose-response curves showing statistically significant hormesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our discovery of hormetic curves is in line with estimates of hormetic behaviors in dose-response repositories like Tox21. Our proposed method has been effective in screening for hormesis from large-scale dose-response data, and the visualization method effectively facilitates the interpretation of test results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15593258261486644","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:22:00Z","timestamp":1788913320000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Shape-Restricted Detection of Natural Product Hormesis: A Re-Analysis of Complex Botanical Mixtures"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0866-1634","authenticated-orcid":false,"given":"Ying","family":"Jin","sequence":"first","affiliation":[{"name":"National Institute for Environmental Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Rider","sequence":"additional","affiliation":[{"name":"National Institutes of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Huang","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Scencies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghang","family":"Xia","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Scencies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Langevin","sequence":"additional","affiliation":[{"name":"University of Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Institute for Environmental Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4387-0271","authenticated-orcid":false,"given":"Daniel","family":"Zilber","sequence":"additional","affiliation":[{"name":"National Institute for Environmental Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-008-8037-y"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21050559"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.14573\/altex.1803011"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/aivt.2018.0020"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-017-0013-z"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105526"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1905136"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.15698\/mic2014.05.145"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2018.12.020"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-112122-104310"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3180.1989.tb00845.x"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1897\/05-014R.1"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13571-020-00246-7"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177012761"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1214\/08-AOAS167"},{"issue":"2","key":"e_1_3_5_17_2","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"Holm S","year":"1979","unstructured":"Holm S. 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