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The Use of MPS in Three Rs and Regulatory Applications: Perspectives From Developers on Stakeholder Responsibilities. MPS在三个r中的使用和监管应用:来自开发商对利益相关者责任的观点。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1177/02611929241310566
Megan R LaFollette, Szczepan W Baran, J Lowry Curley, Anne M Dickinson, Trivia Frazier, Nina Hobi, Ming-I Huang, Victoria Hutter, Benoît G C Maisonneuve, Graham A Marsh, Rhamiya Mahendran, Iris Müller, Xiaohua Qian, Dharaminder Singh, William R Thelin, Jelena Vukasinovic, Pelin L Candarlioglu, Clive S Roper

Increasing the use of microphysiological systems (MPS) in Three Rs and regulatory applications is a nuanced but important goal, which would also help increase their scientific impact. There are three distinct and important stakeholder groups that each play a unique role in expediting the use of MPS for regulatory purpose - namely, commercial MPS developers, end-users and regulators. Additionally, non-profit organisations, such as the 3Rs Collaborative (3RsC), can help coordinate these efforts. This paper introduces the MPS Initiative, as organised by the 3RsC, and clarifies the potential for MPS to benefit all Three Rs. Key differences in the use of MPS-derived data for regulatory evidence of efficacy versus safety, and for various other contexts of use, are discussed. Finally, the results are presented from a survey of primarily commercial MPS developers, that collected their views on the realistic responsibilities of each stakeholder group. The results also highlight their key perspectives on the use of MPS, in the context of Three Rs and regulatory applications.

在3r和监管应用中增加微生理系统(MPS)的使用是一个微妙但重要的目标,这也将有助于提高它们的科学影响。有三个不同而重要的利益相关者群体,每个群体在加速MPS用于监管目的方面都发挥着独特的作用——即商业MPS开发商、最终用户和监管机构。此外,非营利组织,如3r协作组织(3RsC),可以帮助协调这些努力。本文介绍了由3RsC组织的MPS倡议,并阐明了MPS对所有三个Rs有利的潜力。讨论了将MPS衍生数据用于有效性与安全性的监管证据以及各种其他使用情况的关键差异。最后,结果来自于对主要商业MPS开发者的调查,收集了他们对每个利益相关者群体的现实责任的看法。研究结果还强调了他们在3r和监管应用的背景下对MPS使用的关键观点。
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引用次数: 0
Spotlight on Three Rs Progress. 聚焦“三个r”进展。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 DOI: 10.1177/02611929241308666
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引用次数: 0
Report of the First ONTOX Hackathon: Hack to Save Lives and Avoid Animal Suffering. The Use of Artificial Intelligence in Toxicology - A Potential Driver for Reducing/Replacing Laboratory Animals in the Future. 第一ONTOX黑客马拉松报告:黑客拯救生命,避免动物痛苦。人工智能在毒理学中的应用——未来减少/取代实验动物的潜在驱动力。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-12-18 DOI: 10.1177/02611929241305112
Michael G Diemar, Cyrille A M Krul, Marc Teunis, Francois Busquet, Helena Kandarova, Julia D Zajac, Mathieu Vinken, Erwin L Roggen

The first ONTOX Hackathon of the EU Horizon 2020-funded ONTOX project was held on 21-23 April 2024 in Utrecht, The Netherlands (https://ontox-project.eu/hackathon/). This participatory event aimed to collectively advance innovation for human safety through the use of Artificial Intelligence (AI), and hence significantly reduce reliance on animal-based testing. Expert scientists, industry leaders, young investigators, members of animal welfare organisations and academics alike, joined the hackathon. Eight teams were stimulated to find innovative solutions for challenging themes, that were selected based on previous discussions between stakeholders, namely: How to drive the use of AI in chemical risk assessment?; To predict or protect?; How can we secure human health and environmental protection at the same time?; and How can we facilitate the transition from animal tests to full implementation of human-relevant methods? The hackathon ended with a pitching contest, where the teams presented their solutions to a jury. The most promising solutions will be presented to regulatory authorities, industry, academia and non-governmental organisations at the next ONTOX Stakeholder Network meeting and taken up by the ONTOX project in order to tackle the above-mentioned challenges further. This report comprises two parts: The first part highlights some of the lessons learnt during the planning and execution of the hackathon; the second part presents the outcome of the ONTOX Hackathon, which resulted in several innovative and promising solutions based on New Approach Methodologies (NAMs), and outlines ONTOX's intended way forward.

欧盟地平线2020资助的ONTOX项目的第一届ONTOX黑客马拉松于2024年4月21日至23日在荷兰乌得勒支举行(https://ontox-project.eu/hackathon/)。这一参与性活动旨在通过使用人工智能(AI)共同推进人类安全创新,从而显著减少对动物试验的依赖。专家科学家、行业领袖、年轻的调查人员、动物福利组织成员和学者都参加了黑客马拉松。八个团队受到激励,为具有挑战性的主题找到创新的解决方案,这些解决方案是根据利益相关者之前的讨论选出的,即:如何推动人工智能在化学品风险评估中的应用?预测或保护?我们怎样才能同时保证人类健康和环境保护?以及我们如何促进从动物试验到全面实施与人体相关的方法的过渡?黑客马拉松以一场投球比赛结束,参赛团队向评审团展示了他们的解决方案。最有希望的解决方案将在下一次ONTOX利益相关者网络会议上提交给监管机构、行业、学术界和非政府组织,并由ONTOX项目采纳,以进一步应对上述挑战。本报告由两部分组成:第一部分重点介绍在策划和执行黑客马拉松过程中汲取的一些经验教训;第二部分介绍了ONTOX黑客马拉松的成果,该成果产生了基于新方法方法(NAMs)的几种创新和有前途的解决方案,并概述了ONTOX的预期前进方向。
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引用次数: 0
The Use of an In Chemico Digestibility Assay to Reduce the In Vivo Fish Bioaccumulation Testing of Nanomaterials. 利用化学消化率试验减少纳米材料在体内的鱼类生物积累试验。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-12-11 DOI: 10.1177/02611929241304972
Craig McHardy, Nathaniel J Clark, Robert Clough, Richard D Handy

Currently for engineered nanomaterials (ENMs), there are no alternatives to bioaccumulation testing in fish as prescribed by OECD TG 305. New approaches are being sought, in order to reduce the numbers of animals used and address the ethical concerns associated with the use of vertebrates in such testing. This study aimed to demonstrate the value of an alternative method - the in chemico digestibility assay - as a tool to assess the bioaccumulation potential of ENMs. Titanium dioxide ENMs, or their equivalent bulk form, were incorporated onto a commercial fish diet and the fish digestion process was simulated in vitro at pH 2 (simulated stomach phase) and pH 7.8 (simulated intestinal phase). Only the 1000 mg/kg dry weight feed treatment showed measurable Ti release in the stomach phase, with the results being similar for the TiO2 ENM and the bulk form. More Ti from TiO2 was released from the feed during the intestinal phase of digestion compared to the stomach phase, but there were no statistically significant differences between either the ENM or bulk form. There was higher incidental Ti release from untreated control feed in the intestinal phase compared to the stomach phase. On a percentage basis, the stomach generally showed a statistically significant digestibility of around 3% of the total Ti in the feed, compared to around 7% in the intestine. The in chemico digestibility assay shows potential for use in the determination of the bioaccessible fraction of ENMs, and could be a useful screening tool to identify ENMs of concern for bioaccumulation.

目前,对于工程纳米材料(enm),除了经合组织TG 305规定的在鱼类中进行生物积累试验之外,没有其他选择。人们正在寻求新的方法,以减少使用动物的数量,并解决与在此类试验中使用脊椎动物有关的伦理问题。本研究旨在证明一种替代方法的价值-化学消化率测定-作为评估enm生物积累潜力的工具。将二氧化钛enm或其等效散装形式加入到商品鱼饲料中,并在pH为2(模拟胃期)和pH为7.8(模拟肠期)的条件下模拟鱼的体外消化过程。只有1000 mg/kg干重饲料处理在胃相中显示出可测量的Ti释放,TiO2 ENM和散装形式的结果相似。与胃相相比,肠道消化阶段从饲料中释放出更多的TiO2,但ENM和散装形态之间均无统计学差异。未处理对照饲料在肠期的偶发Ti释放量高于胃期。从百分比来看,胃的消化率总体上具有统计学意义,约为饲料中总钛的3%,而肠道的消化率约为7%。化学消化率测定显示出用于测定enm的生物可及性部分的潜力,并可能是一种有用的筛选工具,以确定关注的生物积累的enm。
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引用次数: 0
Resources Round-up. 资源聚集。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-23 DOI: 10.1177/02611929241308667
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引用次数: 0
Conference Diary. 会议的日记。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-23 DOI: 10.1177/02611929241308629
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引用次数: 0
Editorial. 社论。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-13 DOI: 10.1177/02611929241308669
Judith C Madden
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引用次数: 0
A Comparison of European Union and Turkish Reports on the Statistics of Experimental Animal Use in Toxicity Testing. 欧盟和土耳其关于毒性测试中实验动物使用统计报告的比较。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-01 Epub Date: 2024-10-04 DOI: 10.1177/02611929241286885
Cagri Caglar Sinmez, Aşkın Yaşar, Rene van den Hoven

The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK data after Brexit for 2020 were included too). The total number of listed vertebrates used for regulatory toxicity testing in the full 6-year reporting period in Turkey was 3.6% of that reported for the EU+. However, these numbers showed an increasing trend over the reporting period in Turkey, while the trend decreased in the EU+. In the top three most-used species for regulatory toxicology purposes in Turkey, 41% were fish (68,758 animals), followed by rats (29%; 49,975 animals), and then mice (20%; 33,292 animals). Turkey used low numbers of cats and dogs, while the corresponding number for the EU+ was more than 70-fold higher. Non-human primates were not used at all in Turkey, whereas about 34,000 were used in EU+ laboratories. The majority of toxicity tests (57%) performed in Turkey were categorised as 'Other' toxicity tests, and 27% were acute and sub-acute toxicity tests. Successful replacement alternatives (e.g. in vitro and in silico approaches) are already used in a wide range of research areas. However, although this new research and testing paradigm is underpinned by scientific evidence, the legislation and pace of acceptance of these new techniques in Turkey is considerably lagging behind other countries.

对土耳其和欧盟成员国加挪威(EU+)在2015年至2020年期间用于实验目的的动物数量进行了比较(英国脱欧后2020年的数据也包括在内),尤其侧重于监管毒性研究。在整个6年报告期内,土耳其用于监管毒性测试的列名脊椎动物总数是欧盟+报告总数的3.6%。不过,在报告期内,土耳其的这些数量呈上升趋势,而欧盟+则呈下降趋势。在土耳其毒理学监管中使用最多的前三个物种中,41%是鱼(68,758只),其次是大鼠(29%;49,975只),然后是小鼠(20%;33,292只)。土耳其使用的猫和狗数量较少,而欧盟+的相应数量则高出 70 多倍。土耳其完全不使用非人灵长类动物,而欧盟+实验室则使用了约 34,000 只。土耳其进行的大多数毒性试验(57%)被归类为 "其他 "毒性试验,27%为急性和亚急性毒性试验。成功的替代方法(如体外和硅学方法)已被广泛应用于多个研究领域。然而,尽管这种新的研究和测试模式有科学依据,但土耳其在立法和接受这些新技术方面的步伐却大大落后于其他国家。
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引用次数: 0
Assessment of a Low-cost Canine Uterine Simulator as a Tool for Teaching the Ovariohysterectomy Technique to Veterinary Students. 评估将低成本犬子宫模拟器作为向兽医专业学生传授卵巢切除术技术的工具。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-01 DOI: 10.1177/02611929241285392
Melissa García González, Juan José Pérez Rivero Cruz Y Celis, Ivonne Michelle Heuze de Icaza, Ángel Raymundo Lozada Gallegos

The acquisition of skills to perform an ovariohysterectomy (OVH) is crucial for veterinary medicine students. It has been demonstrated that the most effective way to develop these skills is through repetitive training on simulators. Unfortunately, commercial simulators are expensive, limiting their use and highlighting the need for the development of more cost-effective alternatives. This study aimed to assess the effectiveness of a low-cost, easily constructed textile-based simulator for the canine ovaries and uterus in training veterinary students on the OVH technique. The impact of tutor guidance on student learning was also assessed. Participants were divided into two groups: simulator and tutor guidance (SG) and simulator only (SO). Each student performed 20 repetitions of the three-clamp OVH technique, and the number of errors and execution time were quantified. The SG group reached the learning curve plateau in terms of minimum errors on the 7th repetition and attained the fastest time on the 6th repetition. The SO group reached the learning curve plateau in terms of minimum errors and attained the fastest time both on the 15th repetition. From individuals in the SG group, there were no requests for tutor guidance from the 11th attempt. This low-cost simulator is ideal for training veterinary students in the early stages of surgical learning, as it effectively facilitates learning the OVH procedure without the use of live animals.

掌握卵巢切除术(OVH)的技能对兽医专业的学生来说至关重要。事实证明,培养这些技能的最有效方法是在模拟器上进行重复训练。遗憾的是,商业模拟器价格昂贵,限制了其使用,因此需要开发更具成本效益的替代品。本研究旨在评估一种成本低廉、构造简单的犬卵巢和子宫纺织品模拟器在培训兽医专业学生掌握 OVH 技术方面的效果。研究还评估了导师指导对学生学习的影响。参与者分为两组:模拟器和导师指导组(SG)和仅模拟器组(SO)。每名学生重复 20 次三钳夹 OVH 技术,并对错误次数和执行时间进行量化。SG 组在第 7 次重复时达到学习曲线高点,错误次数最少,在第 6 次重复时用时最快。SO 组在第 15 次重复时达到学习曲线高点,错误次数最少,执行时间最快。在 SG 组中,从第 11 次开始就没有人要求辅导员指导。这种模拟器成本低廉,无需使用活体动物,可有效促进 OVH 程序的学习,是兽医专业学生外科学习早期培训的理想选择。
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引用次数: 0
Journeying Through Journals: The Publishing Process and How to Maximise Research Impact. 期刊之旅:出版过程以及如何最大限度地扩大研究影响。
IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-01 Epub Date: 2024-09-26 DOI: 10.1177/02611929241286624
Judith C Madden, Helena Kandarova, Winfried Neuhaus, Nikki Osborne, Alicia Paini, Rita Seabra, Susan Trigwell

Publication is essential to share new ideas, knowledge, or recent findings with those who have an interest in a particular area. Selecting the most appropriate format and timing for dissemination is critical to ensuring the long-term impact of research. However, many researchers, particularly those in the early stages of their career, are unaware of how the publication process works and the different options available for promoting research to maximum effect. Understanding how to maximise impact is particularly important for research using animal models or alternative methods, to make the best use of any animal data generated and reduce animal testing in future. Herein, different publishing models are explained, including anonymised peer review, open review and data sharing initiatives. An overview is given of key resources available to assist authors, reviewers and editors in the process of writing, presenting, reviewing and publishing research. New challenges and opportunities in publishing are discussed, including the potential influence of Artificial Intelligence. A list of 'ten top tips' in publishing for early career researchers is presented, providing advice and recommendations for ensuring a successful and impactful publication record.

要与对某一领域感兴趣的人分享新观点、新知识或最新研究成果,发表论文是必不可少的。选择最合适的传播形式和时机对于确保研究的长期影响至关重要。然而,很多研究人员,尤其是处于职业生涯早期阶段的研究人员,并不知道出版流程是如何运作的,也不知道有哪些不同的选择可以最大限度地推广研究成果。了解如何最大限度地扩大影响对于使用动物模型或替代方法的研究尤为重要,这样才能充分利用所产生的动物数据,并在未来减少动物试验。这里将解释不同的出版模式,包括匿名同行评审、公开评审和数据共享计划。概述了在撰写、介绍、评审和出版研究成果的过程中,可为作者、审稿人和编辑提供帮助的主要资源。讨论了出版方面的新挑战和新机遇,包括人工智能的潜在影响。介绍了职业生涯初期研究人员发表论文的 "十大秘诀",为确保成功发表有影响力的论文提供了意见和建议。
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引用次数: 0
期刊
Atla-Alternatives To Laboratory Animals
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