{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:14:09Z","timestamp":1764688449822},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2005,3,21]],"date-time":"2005-03-21T00:00:00Z","timestamp":1111363200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,3,21]],"date-time":"2005-03-21T00:00:00Z","timestamp":1111363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p><jats:italic>N<\/jats:italic>-acetyltransferase 2 is a polymorphic enzyme in humans. Women who possess homozygous polymorphic alleles have a slower rate of metabolic activation of aryl aromatic amines, one of the constituents of tobacco smoke that has been identified as carcinogenic. We hypothesized that women with breast cancer who were slow acetylators would be at increased risk of breast cancer associated with active and passive exposure to tobacco smoke.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We used a case-only study design to evaluate departure from multiplicativity between acetylation status and smoking status. We extracted DNA from buccal cell samples collected from 502 women with incident primary breast cancer and assigned acetylation status by genotyping ten single-nucleotide polymorphisms. Information on tobacco use and breast cancer risk factors was obtained by structured interviews.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We observed no substantial departure from multiplicativity between acetylation status and history of ever having been an active smoking (adjusted odds ratio estimate of departure from multiplicativity = 0.9, 95% confidence interval 0.5 to 1.7) or ever having had passive residential exposure to tobacco smoke (adjusted odds ratio = 0.7, 95% confidence interval 0.4 to 1.5). The estimates for departure from multiplicativity between acetylation status and various measures of intensity, duration, and timing of active and passive tobacco exposure lacked consistency and were generally not supportive of the idea of a gene\u2013environment interaction.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>In this, the largest case-only study to evaluate the interaction between acetylation status and active or passive exposure to tobacco smoke, we found little evidence to support the idea of a departure from multiplicativity.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr1013","type":"journal-article","created":{"date-parts":[[2005,3,22]],"date-time":"2005-03-22T07:16:03Z","timestamp":1111475763000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A case-only analysis of the interaction between N-acetyltransferase 2 haplotypes and tobacco smoke in breast cancer etiology"],"prefix":"10.1186","volume":"7","author":[{"given":"Timothy L","family":"Lash","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian D","family":"Bradbury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jemma B","family":"Wilk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Aschengrau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,3,21]]},"reference":[{"key":"1011_CR1","first-page":"453","volume-title":"Environ Health Perspect","author":"DH Phillips","year":"1996","unstructured":"Phillips DH: DNA adducts in human tissues: biomarkers of exposure to carcinogens in tobacco smoke. Environ Health Perspect. 1996, 453-458."},{"key":"1011_CR2","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1289\/ehp.95103156","volume":"103","author":"P Vineis","year":"1995","unstructured":"Vineis P, Caporaso N: Tobacco and cancer: epidemiology and the laboratory. Environ Health Perspect. 1995, 103: 154-156.","journal-title":"Environ Health Perspect"},{"key":"1011_CR3","first-page":"37","volume":"948","author":"DW Hein","year":"1988","unstructured":"Hein DW: Acetylator genotype and arylamine-induced carcinogenesis. Biochim Biophys Acta. 1988, 948: 37-66.","journal-title":"Biochim Biophys Acta"},{"key":"1011_CR4","first-page":"29","volume":"9","author":"DW Hein","year":"2000","unstructured":"Hein DW, Doll MA, Fretland AJ, Leff MA, Webb SJ, Xiao GH, Devanaboyina US, Nangju NA, Feng Y: Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev. 2000, 9: 29-42.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR5","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1089\/dna.1990.9.193","volume":"9","author":"M Blum","year":"1990","unstructured":"Blum M, Grant DM, McBride W, Heim M, Meyer UA: Human arylamine N-acetyltransferase genes: isolation, chromosomal localization and functional expression. DNA Cell Biol. 1990, 9: 193-203.","journal-title":"DNA Cell Biol"},{"key":"1011_CR6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0027-5107(02)00153-7","volume":"30","author":"DW Hein","year":"2002","unstructured":"Hein DW: Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutat Res. 2002, 30: 65-77.","journal-title":"Mutat Res"},{"key":"1011_CR7","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.1093\/nar\/17.10.3978","volume":"17","author":"DM Grant","year":"1989","unstructured":"Grant DM, Blum M, Demierre A, Meyer UA: Nucleotide sequence of an intronless gene for a human arylamine N-acetyltransferase related to polymorphic drug acetylation. Nucleic Acids Res. 1989, 17: 3978-","journal-title":"Nucleic Acids Res"},{"key":"1011_CR8","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0163-7258(89)90036-3","volume":"42","author":"DA Evans","year":"1989","unstructured":"Evans DA: N-acetyltransferase. Pharmacol Ther. 1989, 42: 157-234. 10.1016\/0163-7258(89)90036-3.","journal-title":"Pharmacol Ther"},{"key":"1011_CR9","doi-asserted-by":"publisher","first-page":"5237","DOI":"10.1073\/pnas.88.12.5237","volume":"88","author":"M Blum","year":"1991","unstructured":"Blum M, Demierre A, Grant DM, Heim M, Meyer UA: Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc Natl Acad Sci. 1991, 88: 5237-5241.","journal-title":"Proc Natl Acad Sci"},{"key":"1011_CR10","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1093\/carcin\/14.8.1633","volume":"14","author":"DW Hein","year":"1993","unstructured":"Hein DW, Doll MA, Rustan TD, Gray K, Feng Y, Ferguson RJ, Grant DM: Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis. 1993, 14: 1633-1638.","journal-title":"Carcinogenesis"},{"key":"1011_CR11","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/ajmg.1320570413","volume":"57","author":"I Cascorbi","year":"1995","unstructured":"Cascorbi I, Drakoulis N, Brockmoller J, Maurer A, Sperling K, Roots I: Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet. 1995, 57: 581-592.","journal-title":"Am J Hum Genet"},{"key":"1011_CR12","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1001\/jama.1996.03540180050032","volume":"276","author":"CB Ambrosone","year":"1996","unstructured":"Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Michalek AM, Laughlin R, Nemoto T, Gillenwater KA, Shields PG: Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA. 1996, 276: 1494-1501. 10.1001\/jama.276.18.1494.","journal-title":"JAMA"},{"key":"1011_CR13","first-page":"83","volume":"396","author":"CB Ambrosone","year":"1997","unstructured":"Ambrosone CB, Shields PG: Molecular epidemiology of breast cancer. Prog Clin Biol Res. 1997, 396: 83-99.","journal-title":"Prog Clin Biol Res"},{"key":"1011_CR14","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1097\/00008571-200307000-00005","volume":"13","author":"OL van der Hel","year":"2003","unstructured":"van der Hel OL, Peeters PH, Hein DW, Doll MA, Grobbee DE, Kromhout D, Bueno de Mesquita HB: NAT2 slow acetylation and GSTM1 null genotypes may increase postmenopausal breast cancer risk in long-term smoking women. Pharmacogenetics. 2003, 13: 399-407. 10.1097\/00008571-200307000-00005.","journal-title":"Pharmacogenetics"},{"key":"1011_CR15","first-page":"371","volume":"7","author":"RC Millikan","year":"1998","unstructured":"Millikan RC, Pittman GS, Newman B, Tse CK, Selmin O, Rockhill B, Savitz D, Moorman PG, Bell DA: Cigarette smoking, N-Acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998, 7: 371-378.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR16","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1093\/carcin\/18.11.2127","volume":"18","author":"DJ Hunter","year":"1997","unstructured":"Hunter DJ, Hankinson SE, Hough H, Gertig DM, Garcia-Closas M, Spiegelman D, Manson JE, Colditz GA, Willett WC, Speizer FE, et al: A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis. 1997, 18: 2127-2132. 10.1093\/carcin\/18.11.2127.","journal-title":"Carcinogenesis"},{"key":"1011_CR17","first-page":"953","volume":"11","author":"PD Terry","year":"2002","unstructured":"Terry PD, Rohan TE: Cigarette smoking and the risk of breast cancer in women: A review of the literature. Cancer Epidemiol Biomarkers Prev. 2002, 11: 953-71.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/oxfordjournals.epirev.a036098","volume":"15","author":"J Palmer","year":"1993","unstructured":"Palmer J, Rosenberg L: Cigarette smoking and the risk of breast cancer. Epidemiol Rev. 1993, 15: 145-156.","journal-title":"Epidemiol Rev"},{"key":"1011_CR19","first-page":"1","volume":"2","author":"A Morabia","year":"2000","unstructured":"Morabia A, Bernstein M: A review of the relation of smoking (active and passive) and breast cancer. J Women's Cancer. 2000, 2: 1-9.","journal-title":"J Women's Cancer"},{"key":"1011_CR20","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1093\/oxfordjournals.aje.a008835","volume":"143","author":"A Morabia","year":"1996","unstructured":"Morabia A, Bernstein M, Heritier S, Khatchatrian N: Relation of breast cancer with passive and active exposure to tobacco smoke. Am J Epidemiol. 1996, 143: 918-928.","journal-title":"Am J Epidemiol"},{"key":"1011_CR21","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/bjc.1994.258","volume":"70","author":"SJ Smith","year":"1994","unstructured":"Smith SJ, Deacon JM, Chilvers CED: Alcohol, smoking, passive smoking and caffeine in relation to breast cancer risk in young women. Br J Cancer. 1994, 70: 112-119.","journal-title":"Br J Cancer"},{"key":"1011_CR22","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/oxfordjournals.aje.a009727","volume":"149","author":"TL Lash","year":"1999","unstructured":"Lash TL, Aschengrau A: Active and passive cigarette smoking and the occurrence of breast cancer. Am J Epidemiol. 1999, 149: 5-12.","journal-title":"Am J Epidemiol"},{"key":"1011_CR23","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1023\/A:1008906105790","volume":"11","author":"KC Johnson","year":"2000","unstructured":"Johnson KC, Hu J, Mao Y: Passive and active smoking and breast cancer risk in Canada, 1994\u201397. The Canadian Cancer Registries Epidemiology Research Group. Cancer Causes Control. 2000, 11: 211-221. 10.1023\/A:1008906105790.","journal-title":"Cancer Causes Control"},{"key":"1011_CR24","first-page":"698","volume":"11","author":"J Chang-Claude","year":"2002","unstructured":"Chang-Claude J, Kropp S, Jager B, Bartsch H, Risch A: Differential effect of NAT2 on the association between active and passive smoke exposure and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2002, 11: 698-704.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR25","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1093\/aje\/152.3.226","volume":"152","author":"A Morabia","year":"2000","unstructured":"Morabia A, Bernstein MS, Bouchardy I, Kurtz J, Morris MA: Breast cancer and active and passive smoking: The role of the N-acetyltransferase 2 genotype. Am J Epidemiol. 2000, 152: 226-232. 10.1093\/aje\/152.3.226.","journal-title":"Am J Epidemiol"},{"key":"1011_CR26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1289\/ehp.4980","volume":"111","author":"A Aschengrau","year":"2003","unstructured":"Aschengrau A, Roger S, Ozonoff D: Perchloroethylene-contaminated drinking water and the risk of breast cancer: additional results from Cape Cod, Massachusetts, USA. Environ Health Perspect. 2003, 111: 167-173.","journal-title":"Environ Health Perspect"},{"key":"1011_CR27","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1200\/JCO.2002.08.137","volume":"20","author":"RA Silliman","year":"2002","unstructured":"Silliman RA, Guadagnoli E, Rakowski W, Landrum MB, Lash TL, Wolf R, Fink A, Ganz PA, Gurwitz J, Borbas C, et al: Adjuvant tamoxifen prescription in women 65 years and older with early stage breast cancer. J Clin Oncol. 2002, 20: 2680-1688. 10.1200\/JCO.2002.08.137.","journal-title":"J Clin Oncol"},{"key":"1011_CR28","doi-asserted-by":"crossref","first-page":"18140","DOI":"10.1016\/S0021-9258(19)37164-9","volume":"267","author":"T Deguchi","year":"1992","unstructured":"Deguchi T: Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver. J Biol Chem. 1992, 267: 18140-18147.","journal-title":"J Biol Chem"},{"key":"1011_CR29","doi-asserted-by":"publisher","first-page":"5237","DOI":"10.1073\/pnas.88.12.5237","volume":"88","author":"M Blum","year":"1991","unstructured":"Blum M, Demierre A, Grant DM, Heim M, Meyers UA: Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc Natl Acad Sci USA. 1991, 88: 5237-5241.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1011_CR30","doi-asserted-by":"publisher","first-page":"6333","DOI":"10.1073\/pnas.88.14.6333","volume":"88","author":"KP Vatsis","year":"1991","unstructured":"Vatsis KP, Martell KJ, Weber WW: Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc Natl Acad Sci USA. 1991, 88: 6333-6337.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1011_CR31","doi-asserted-by":"crossref","first-page":"4630","DOI":"10.1016\/S0021-9258(19)39609-7","volume":"265","author":"S Ohsako","year":"1990","unstructured":"Ohsako S, Deguchi T: Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferase from human liver. J Biol Chem. 1990, 265: 4630-4634.","journal-title":"J Biol Chem"},{"key":"1011_CR32","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1097\/00008571-199606000-00009","volume":"6","author":"I Cascorbi","year":"1996","unstructured":"Cascorbi I, Brockmoller J, Bauer S, Reum T, Roots I: NAT2*12A (803\u2192G) codes for rapid arylamine N-acetylation in humans. Pharmacogenetics. 1996, 6: 257-259.","journal-title":"Pharmacogenetics"},{"key":"1011_CR33","first-page":"827","volume":"52","author":"HJ Lin","year":"1993","unstructured":"Lin HJ, Han CY, Lin BK, Hardy S: Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics and whites: application to metabolic epidemiology. Am J Hum Genet. 1993, 52: 827-834.","journal-title":"Am J Hum Genet"},{"key":"1011_CR34","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1097\/00008571-199210000-00004","volume":"2","author":"D Hickman","year":"1992","unstructured":"Hickman D, Risch A, Camilleri JP, Sim E: Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants. Pharmacogenetics. 1992, 2: 217-226.","journal-title":"Pharmacogenetics"},{"key":"1011_CR35","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1093\/carcin\/14.8.1689","volume":"14","author":"DA Bell","year":"1993","unstructured":"Bell DA, Taylor JA, Butler MA, Stephens EA, Wiest J, Brubaker LH, Kadlubar FF, Lucier GW: Genotype\/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis. 1993, 14: 1689-1692.","journal-title":"Carcinogenesis"},{"key":"1011_CR36","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/369154a0","volume":"369","author":"P Vineis","year":"1994","unstructured":"Vineis P, Bartsch H, Caporaso N, Harrington AM, Kadlubar FF, Landi MT, Malaveille C, Shields PG, Skipper P, Talaska G, et al: Genetically based N-acetyltransferase metabolic polymorphisms and low-level environmental exposure to carcinogens. Nature. 1994, 369: 154-156. 10.1038\/369154a0.","journal-title":"Nature"},{"key":"1011_CR37","volume-title":"SAS. Version 8","author":"SAS Institute Inc","year":"1999","unstructured":"SAS Institute Inc: SAS. Version 8. 1999, Cary, NC: SAS Institute"},{"key":"1011_CR38","first-page":"567","volume":"4","author":"GA Colditz","year":"1995","unstructured":"Colditz GA, Frazier AL: Models of breast cancer show that risk is set by events of early life: prevention efforts must shift focus. Cancer Epidemiol Biomarkers Prev. 1995, 4: 567-571.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR39","first-page":"353","volume":"3","author":"J Russo","year":"1994","unstructured":"Russo J, Russo IH: Toward a physiological approach to breast cancer prevention. Cancer Epidemiol Biomarkers Prev. 1994, 3: 353-364.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1011_CR40","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1093\/oxfordjournals.aje.a113025","volume":"112","author":"S Greenland","year":"1980","unstructured":"Greenland S: The effect of misclassification in the presence of covariates. Am J Epidemiol. 1980, 112: 564-569.","journal-title":"Am J Epidemiol"},{"key":"1011_CR41","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/S0140-6736(01)06418-2","volume":"358","author":"D Clayton","year":"2001","unstructured":"Clayton D, McKeigue PM: Epidemiologic methods for studying genes and environmental factors in complex diseases. Lancet. 2001, 358: 1356-1360. 10.1016\/S0140-6736(01)06418-2.","journal-title":"Lancet"},{"key":"1011_CR42","first-page":"332","volume-title":"Modern Epidemiology","author":"S Greenland","year":"1998","unstructured":"Greenland S, Rothman KJ: Concepts of interaction. Modern Epidemiology. Edited by: Rothman K, Greenland S. 1998, Philadelphia, PA: Lippincott-Raven, 332-336. 2","edition":"2"},{"key":"1011_CR43","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1093\/aje\/154.8.687","volume":"154","author":"PS Albert","year":"2001","unstructured":"Albert PS, Ratnasignghe D, Tangrea J, Wacholder S: Limitations of the case-only design for identifying gene-environment interactions. Am J Epidemiol. 2001, 154: 687-693. 10.1093\/aje\/154.8.687.","journal-title":"Am J Epidemiol"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr1013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/bcr1013\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/bcr1013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T11:00:12Z","timestamp":1728385212000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/bcr1013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,21]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2005,6]]}},"alternative-id":["1011"],"URL":"https:\/\/doi.org\/10.1186\/bcr1013","relation":{},"ISSN":["1465-542X"],"issn-type":[{"type":"electronic","value":"1465-542X"}],"subject":[],"published":{"date-parts":[[2005,3,21]]},"assertion":[{"value":"10 August 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2005","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2005","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2005","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R385"}}