{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:00:16Z","timestamp":1788210016969,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eye"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1038\/s41433-019-0340-3","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T09:06:11Z","timestamp":1549962371000},"page":"679-682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves\u2019 orbitopathy"],"prefix":"10.1038","volume":"33","author":[{"given":"Jonathan C. P.","family":"Roos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachna","family":"Murthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"340_CR1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1210\/jc.2011-1299","volume":"97","author":"L Zhang","year":"2012","unstructured":"Zhang L, Grennan-Jones F, Lane C, Rees DA, Dayan CM, Ludgate M. Adipose tissue depot-specific differences in the regulation of hyaluronan production of relevance to Graves\u2019 orbitopathy. J Clin Endocrinol Metab. 2012;97:653\u201362.","journal-title":"J Clin Endocrinol Metab"},{"key":"340_CR2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12890-018-0626-4","volume":"18","author":"M Molina-Molina","year":"2018","unstructured":"Molina-Molina M, Machahua-Huamani C, Vicens-Zygmunt V, Llatj\u00f3s R, Escobar I, Sala-Llinas E, et al. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells. BMC Pulm Med. 2018;18:63.","journal-title":"BMC Pulm Med"},{"key":"340_CR3","doi-asserted-by":"publisher","first-page":"942","DOI":"10.4049\/jimmunol.168.2.942","volume":"168","author":"J Pritchard","year":"2002","unstructured":"Pritchard J, Horst N, Cruikshank W, Smith TJ. Igs from patients with Graves\u2019 disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol. 2002;168:942\u201350.","journal-title":"J Immunol"},{"key":"340_CR4","doi-asserted-by":"publisher","first-page":"15722","DOI":"10.18632\/oncotarget.4652","volume":"6","author":"AT Hillel","year":"2015","unstructured":"Hillel AT, Gelbard A. Unleashing rapamycin in fibrosis. Oncotarget. 2015;6:15722\u20133.","journal-title":"Oncotarget"},{"key":"340_CR5","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1177\/0194599810397750","volume":"144","author":"A Ghosh","year":"2011","unstructured":"Ghosh A, Malaisrie N, Leahy KP, Singhal S, Einhorn E, Howlett P, et al. Cellular adaptive inflammation mediates airway granulation in a murine model of subglottic stenosis. Otolaryngol Head Neck Surg. 2011;144:927\u201333.","journal-title":"Otolaryngol Head Neck Surg"},{"key":"340_CR6","doi-asserted-by":"publisher","first-page":"e33626","DOI":"10.1371\/journal.pone.0033626","volume":"7","author":"G Chen","year":"2012","unstructured":"Chen G, Chen H, Wang C, Peng Y, Sun L, Liu H, et al. Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts. PLoS ONE. 2012;7:e33626.","journal-title":"PLoS ONE"},{"key":"340_CR7","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11748-012-0131-2","volume":"61","author":"SY Yu","year":"2013","unstructured":"Yu SY, Liu L, Li P, Li J. Rapamycin inhibits the mTOR\/p70S6K pathway and attenuates cardiac fibrosis in adriamycin-induced dilated cardiomyopathy. Thorac Cardiovasc Surg. 2013;61:223\u20138.","journal-title":"Thorac Cardiovasc Surg"},{"key":"340_CR8","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1515\/JPEM.2006.19.10.1193","volume":"19","author":"GE Krassas","year":"2006","unstructured":"Krassas GE, Gogakos A. Thyroid-associated ophthalmopathy in juvenile Graves\u2019 disease\u2014clinical, endocrine and therapeutic aspects. J Pediatr Endocrinol Metab. 2006;19:1193\u2013206.","journal-title":"J Pediatr Endocrinol Metab"},{"key":"340_CR9","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","volume":"376","author":"TJ Smith","year":"2017","unstructured":"Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748\u201361.","journal-title":"N Engl J Med"},{"key":"340_CR10","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1097\/IOP.0b013e3180500d57","volume":"23","author":"S Chang","year":"2007","unstructured":"Chang S, Perry JD, Kosmorsky GS, Braun WE. Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy. Ophthalmic Plast Reconstr Surg. 2007;23:225\u20136.","journal-title":"Ophthalmic Plast Reconstr Surg"},{"issue":"2","key":"340_CR11","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41433-018-0303-0","volume":"33","author":"Jonathan C. P. Roos","year":"2018","unstructured":"Roos JCP, Murthy R. Comment on: A British Ophthalmic Surveillance Unit (BOSU) study into dysthyroid optic neuropathy in the United Kingdom. Eye (Lond). 2018; \n                    https:\/\/doi.org\/10.1038\/s41433-018-0303-0\n                    \n                  .","journal-title":"Eye"},{"key":"340_CR12","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1097\/TP.0b013e3182551021","volume":"94","author":"B Nashan","year":"2012","unstructured":"Nashan B, Citterio F. Wound healing complications and the use of mammalian target of rapamycin inhibitors in kidney transplantation: a critical review of the literature. Transplantation. 2012;94:547\u201361.","journal-title":"Transplantation"},{"key":"340_CR13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0161-6420(90)32631-3","volume":"97","author":"R Fitzsimons","year":"1990","unstructured":"Fitzsimons R, White J. Functional scoring of the field of binocular single vision. Ophthalmology. 1990;97:33\u20135.","journal-title":"Ophthalmology"},{"key":"340_CR14","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1210\/jc.2015-2932","volume":"101","author":"L Zhang","year":"2016","unstructured":"Zhang L, Ji QH, Ruge F, Lane C, Morris D, Tee AR, et al. Reversal of pathological features of graves\u2019 orbitopathy by activation of forkhead transcription factors, FOXOs. J Clin Endocrinol Metab. 2016;101:114\u201322.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"340_CR15","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41433-018-0304-z","volume":"33","author":"Tilak Das","year":"2018","unstructured":"Das T, Roos JCP, Patterson AJ, Graves MJ, Murthy R. T2-relaxation mapping and fat fraction assessment to objectively quantify clinical activity in thyroid eye disease: an initial feasibility study. Eye (Lond). 2018; \n                    https:\/\/doi.org\/10.1038\/s41433-018-0304-z\n                    \n                  .","journal-title":"Eye"},{"issue":"2","key":"340_CR16","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41433-018-0242-9","volume":"33","author":"Jonathan C. P. Roos","year":"2018","unstructured":"Roos JCP, Paulpandian V, Murthy R. Serial TSH-receptor antibody levels to guide the management of thyroid eye disease: the impact of smoking, immunosuppression, radio-iodine, and thyroidectomy. Eye (Lond). 2018; \n                    https:\/\/doi.org\/10.1038\/s41433-018-0242-9\n                    \n                  .","journal-title":"Eye"},{"key":"340_CR17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1136\/bjo.73.8.639","volume":"73","author":"MP Mourits","year":"1989","unstructured":"Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves\u2019 ophthalmopathy: a novel approach. Br J Ophthalmol. 1989;73:639\u201344.","journal-title":"Br J Ophthalmol"}],"container-title":["Eye"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0340-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0340-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0340-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:06:23Z","timestamp":1684616783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41433-019-0340-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["340"],"URL":"https:\/\/doi.org\/10.1038\/s41433-019-0340-3","relation":{},"ISSN":["0950-222X","1476-5454"],"issn-type":[{"value":"0950-222X","type":"print"},{"value":"1476-5454","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]},"assertion":[{"value":"7 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors are doctors who manage patients with thyroid eye disease. The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"As an anonymised retrospective report no institutional review board authorisation was necessary.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Ethics statement"}},{"value":"Dr. Murthy serves as guarantor of this work. It is an honest, accurate and transparent account of the study being reported; no important aspects of the study have been omitted.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Guarantor"}}]}}