{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:25:29Z","timestamp":1792898729808,"version":"4.5.0"},"reference-count":27,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017035","name":"Fondation ISREC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016895","name":"Biltema Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","redjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Radiation Oncology*Biology*Physics"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ijrobp.2025.04.021","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:09:03Z","timestamp":1746184143000},"page":"593-601","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines With Pulsed Electron FLASH Radiation Therapy"],"prefix":"10.1016","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-8063","authenticated-orcid":false,"given":"Veljko","family":"Grilj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anet Valdes","family":"Zayas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Sesink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preethi","family":"Devanand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rep\u00e1raz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Paisley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Sprengers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiuska","family":"Passelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pernot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till Tobais","family":"B\u00f6hlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner Walter","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Moeckli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Bailat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Germond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Dagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Bochud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Bourhis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda G.","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ijrobp.2025.04.021_bib0001","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.radonc.2019.04.008","article-title":"Clinical translation of FLASH radiotherapy: Why and how?","volume":"139","author":"Bourhis","year":"2019","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0002","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41571-022-00697-z","article-title":"Towards clinical translation of FLASH radiotherapy","volume":"19","author":"Vozenin","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0003","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1002\/mp.15659","article-title":"Ultra-high dose rate radiation production and delivery systems intended for FLASH","volume":"49","author":"Farr","year":"2022","journal-title":"Med Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-cancerbio-061421-022217","article-title":"Reinventing radiobiology in the light of FLASH radiotherapy","volume":"7","author":"Limoli","year":"2023","journal-title":"Annu Rev Cancer Biol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0005","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1080\/09553002.2021.2004328","article-title":"Understanding the FLASH effect to unravel the potential of ultra-high dose rate irradiation","volume":"98","author":"Kacem","year":"2022","journal-title":"Int J Radiat Biol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0006","doi-asserted-by":"crossref","first-page":"245ra93","DOI":"10.1126\/scitranslmed.3008973","article-title":"Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice","volume":"6","author":"Favaudon","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0007","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.radonc.2017.05.003","article-title":"Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy\/s","volume":"124","author":"Montay-Gruel","year":"2017","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0008","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.radonc.2018.08.016","article-title":"X-rays can trigger the FLASH effect: Ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice","volume":"129","author":"Montay-Gruel","year":"2018","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0009","doi-asserted-by":"crossref","first-page":"10943","DOI":"10.1073\/pnas.1901777116","article-title":"Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species","volume":"116","author":"Montay-Gruel","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0010","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1158\/1078-0432.CCR-20-0894","article-title":"Hypofractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice","volume":"27","author":"Montay-Gruel","year":"2021","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0011","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1667\/RADE-20-00067.1","article-title":"Ultra-high-dose-rate FLASH irradiation limits reactive gliosis in the brain","volume":"194","author":"Montay-Gruel","year":"2020","journal-title":"Radiat Res"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0012","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1667\/RADE-20-00090","article-title":"FLASH irradiation results in reduced severe skin toxicity compared to conventional-dose-rate irradiation","volume":"194","author":"Soto","year":"2020","journal-title":"Radiat Res"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0013","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.radonc.2021.12.022","article-title":"In vivo validation and tissue sparing factor for acute damage of pencil beam scanning proton FLASH","volume":"167","author":"Singers S\u00f8rensen","year":"2022","journal-title":"Radiother Oncol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0014","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.3390\/cancers13051012","article-title":"FLASH proton pencil beam scanning irradiation minimizes radiation-induced leg contracture and skin toxicity in mice","volume":"13","author":"Cunningham","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0015","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-78017-7","article-title":"Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice","volume":"10","author":"Levy","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0016","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.3390\/cancers15072121","article-title":"Independent reproduction of the FLASH effect on the gastrointestinal tract: A multi-institutional comparative study","volume":"15","author":"Vald\u00e9s Zayas","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0017","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.ijrobp.2019.10.049","article-title":"Design, implementation, and in vivo validation of a novel proton FLASH radiation therapy system","volume":"106","author":"Diffenderfer","year":"2020","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0018","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.ijrobp.2024.01.224","article-title":"FLASH proton radiation therapy mitigates inflammatory and fibrotic pathways and preserves cardiac function in a preclinical mouse model of radiation-induced heart disease","volume":"119","author":"Kim","year":"2024","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0019","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ijrobp.2024.04.071","article-title":"Proton FLASH: Impact of dose rate and split dose on acute skin toxicity in a murine model","volume":"120","author":"S\u00f8rensen","year":"2024","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0020","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.ijrobp.2021.08.004","article-title":"Irradiation at ultra-high (FLASH) dose rates reduces acute normal tissue toxicity in the mouse gastrointestinal system","volume":"111","author":"Ruan","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0021","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/mp.12111","article-title":"High dose-per-pulse electron beam dosimetry \u2014 A model to correct for the ion recombination in the advanced Markus ionization chamber","volume":"44","author":"Petersson","year":"2017","journal-title":"Med Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0022","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/acm2.13433","article-title":"Implementation and validation of a beam-current transformer on a medical pulsed electron beam LINAC for FLASH-RT beam monitoring","volume":"22","author":"Oesterle","year":"2021","journal-title":"J Appl Clin Med Phys."},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0023","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1002\/mp.15474","article-title":"Technical note: Validation of an ultrahigh dose rate pulsed electron beam monitoring system using a current transformer for FLASH preclinical studies","volume":"49","author":"Gon\u00e7alves Jorge","year":"2022","journal-title":"Med Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0024","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/mp.12066","article-title":"High dose-per-pulse electron beam dosimetry: Usability and dose-rate independence of EBT3 Gafchromic films","volume":"44","author":"Jaccard","year":"2017","journal-title":"Med Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0025","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.ijrobp.2024.10.009","article-title":"Redefining FLASH radiation therapy: The impact of mean dose rate and dose per pulse in the gastrointestinal tract","volume":"121","author":"Liu","year":"2025","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0026","doi-asserted-by":"crossref","DOI":"10.1088\/1361-6560\/ace877","article-title":"Mean dose rate in ultra-high dose rate electron irradiation is a significant predictor for O2 consumption and H2 O2 yield","volume":"68","author":"Sunnerberg","year":"2023","journal-title":"Phys Med Biol"},{"key":"10.1016\/j.ijrobp.2025.04.021_bib0027","doi-asserted-by":"crossref","DOI":"10.1016\/j.radphyschem.2024.111887","article-title":"Average dose rate is the primary determinant of lipid peroxidation in liposome membranes exposed to pulsed electron FLASH beam","volume":"222","author":"Grilj","year":"2024","journal-title":"Radiat Phys Chem"}],"container-title":["International Journal of Radiation Oncology*Biology*Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S036030162500389X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S036030162500389X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T22:50:46Z","timestamp":1762296646000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S036030162500389X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S036030162500389X"],"URL":"https:\/\/doi.org\/10.1016\/j.ijrobp.2025.04.021","relation":{},"ISSN":["0360-3016"],"issn-type":[{"value":"0360-3016","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines With Pulsed Electron FLASH Radiation Therapy","name":"articletitle","label":"Article Title"},{"value":"International Journal of Radiation Oncology*Biology*Physics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijrobp.2025.04.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}