Animal Research: Reporting in vivo Experiments—The ARRIVE Guidelines:
05 Jan 2011-Journal of Cerebral Blood Flow and Metabolism (SAGE Publications)-Vol. 31, Iss: 4, pp 991-993
TL;DR: The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al.
Abstract: The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010).
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TL;DR: Most of the papers surveyed did not report using randomisation or blinding to reduce bias in animal selection and outcome assessment, consistent with reviews of many research areas, including clinical studies, published in recent years.
Abstract: animals used (i.e., species/strain, sex, and age/weight). Most of the papers surveyed did not report using randomisation (87%) or blinding (86%) to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods fully described them and presented the results with a measure of precision or variability [5]. These findings are a cause for concern and are consistent with reviews of many research areas, including clinical studies, published in recent years [2–22].
6,271 citations
Queen Mary University of London1, Durham University2, University of Bristol3, Charité4, National Institutes of Health5, Liverpool School of Tropical Medicine6, University of Southampton7, University of Tasmania8, AstraZeneca9, University of Edinburgh10, Cardiff University11, Medical Research Council12, University of Florida13, University of Sydney14, Janssen Pharmaceutica15, University of Bern16
TL;DR: The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) have been updated and information reorganised to facilitate their use in practice to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
Abstract: Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
1,796 citations
TL;DR: It is shown that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants, and that IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis.
Abstract: Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Additionally, IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and an impact of the intestinal flora and meningeal IL-17(+) γδ T cells on ischemic injury.
663 citations
Royal Society1, University College London2, University of Nottingham3, University of Naples Federico II4, Royal College of Surgeons in Ireland5, Swansea University6, University of California, San Diego7, Nanjing Medical University8, Rutgers University9, La Trobe University10, University of British Columbia11, University of Reading12, Universidade Federal de Minas Gerais13, Queen Mary University of London14
TL;DR: The BJP has been and remains an active advocate of the ARRIVE guidelines and the Editor in Chief of the BJP is a member of the new team that was assembled, which triggered a reappraisal of the guidelines led by the NC3Rs who, in 2018, established a new, international Working Group to review and update the ARrIVE guidelines.
Abstract: The BJP has been and remains an active advocate of the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010a) that were established by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in 2010. The ARRIVE guidelines need no introduction and we will not rehearse the arguments in depth here, other than to restate that the lack of key in vivo experimental details has been identified as a major contributing factor to the poor reproducibility of pre-clinical research. This fact was the primary driver for establishment by the NC3Rs of the first version of the ARRIVE guidelines. ARRIVE provided a 20-point checklist, specifying all of the experimental details (procedures and fixed factors) that should be included in manuscripts for proper reporting of animal research. The guidelines were rapidly endorsed internationally by funding bodies, universities, learned societies and, importantly, Life Science journals. Currently there are 1,046 journals endorsing ARRIVE including BJP, which was one of the original six influential journals that published the guidelines in full in 2010 (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010b). However, ARRIVE has not had the effect that was originally hoped for, despite this widespread support and endorsement. In 2016 and in 2018 assessments of adherence of articles published in endorsing journals identified a lack of engagement. As an example, one systematic review of reports of studies investigating acute lung injury revealed that, of the items expected for ARRIVE compliance, only 45% of those advised for inclusion in the Methods, and only 29% of those for inclusion in the Results section, were present (Avey et al., 2016). Moreover, formal endorsement of the ARRIVE guidelines by journals did not necessarily improve compliance (Leung, Rousseau-Blass, Beauchamp, & Pang, 2018). Such disappointing reports of outcome triggered a reappraisal of the guidelines led by the NC3Rs who, in 2018, established a new, international Working Group to review and update the ARRIVE guidelines to generate ARRIVE 2.0 (Percie du Sert et al., 2018). As with the team of experts brought together to establish the first iteration of ARRIVE, the Editor in Chief of the BJP is a member of the new team that was assembled. As such, the BJP has been well-placed to influence the content, testing and final publication of both iterations of the guidelines. In 2015, the BJP published an editorial reporting findings from a survey of compliance with ARRIVE in articles published in 2014 in two issues of the journal (McGrath & Lilley, 2015). The results were not as had been hoped for, as was also evident from assessments elsewhere, and revealed scope for improving compliance in respect of both the design of the (animal) experiments and the description of experimental procedures. To help remedy this problem, a checklist was developed that provided an aide memoire of the details of the animals and research procedures that should be reported in manuscripts submitted to the journal. A further editorial focussed on experimental design and data analysis (Curtis et al., 2018) for all types of experimental data published in the journal, including those emanating from experiments with animals, was also published. A key issue with many of the studies reported in BJP prior to this related to inadequate experimental design and inappropriate statistical analysis. At the same time, the Instructions to Authors were revised, to include the new rubric, and the editorial scrutiny of these aspects of the peer review process was tightened up. As a further prompt, in 2016, authors were required to make a Declaration as part of the submission process, to confirm that their manuscript was ARRIVE compliant. In addition to these measures, two new ‘specialist’ editors were appointed: a Design & Analysis Advisor and a Consulting Editor in ARRIVE Guidelines and Animal Welfare. The brief of the latter was to monitor ARRIVE compliance in BJP publications and to assist Senior Editors with their appraisal of manuscripts. All these changes still remain in place with the addition of a Consulting Editor in Statistical Analysis to ensure that the research reports match BJP criteria and so qualify for publication.
481 citations
TL;DR: MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size, which indicates that MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
Abstract: Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).
MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
380 citations
References
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TL;DR: The Consort 2010 Statement as discussed by the authors has been used worldwide to improve the reporting of randomised controlled trials and has been updated by Schulz et al. in 2010, based on new methodological evidence and accumulating experience.
Abstract: The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials.
11,165 citations
TL;DR: Most of the papers surveyed did not report using randomisation or blinding to reduce bias in animal selection and outcome assessment, consistent with reviews of many research areas, including clinical studies, published in recent years.
Abstract: animals used (i.e., species/strain, sex, and age/weight). Most of the papers surveyed did not report using randomisation (87%) or blinding (86%) to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods fully described them and presented the results with a measure of precision or variability [5]. These findings are a cause for concern and are consistent with reviews of many research areas, including clinical studies, published in recent years [2–22].
6,271 citations
TL;DR: The 2010 version of the CONSORT Statement is described, which updates the previous reporting guideline based on new methodological evidence and accumulated experience.
Abstract: Kenneth Schulz and colleagues describe the 2010 version of the CONSORT Statement, which updates the previous reporting guideline based on new methodological evidence and accumulated experience.
5,090 citations
"Animal Research: Reporting in vivo ..." refers background in this paper
...…analysed 15 (a) Report the number of animals in each group included in each analysis; report absolute numbers (e.g., 10/20, not 50% (Schulz et al, 2010)); (b) if any animals or data were not included in the analysis, explain why Outcomes and estimation 16 Report the results for…...
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...…study limitations, including any potential sources of bias, any limitations of the animal model, and the imprecision associated with the results (Schulz et al, 2010); (c) describe any implications of your experimental methods or findings for the replacement, refinement, or reduction (the 3Rs)…...
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TL;DR: 1.2 Provide an accurate summary of the background, res principal findings, and conclusions of the study.
1,487 citations
"Animal Research: Reporting in vivo ..." refers background or methods in this paper
...Item Recommendation (Kilkenny et al, 2010) Title 1 Provide as accurate and concise a description of the content of the article as possible Abstract 2 Provide an accurate summary of the background, research objectives (including details of the species or strain of animal used), key methods,…...
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...To view Continued Item Recommendation (Kilkenny et al, 2010) Sample size 10 (a) Specify the total number of animals used in each experiment and the number of animals in each experimental group; (b) explain how the number of animals was decided; provide details of any sample size calculation used;…...
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...To view Continued Item Recommendation (Kilkenny et al, 2010) Sample size 10 (a) Specify the total number of animals used in each experiment and the number of animals in each experimental group; (b) explain how the number of animals was decided; provide details of any sample size calculation used; (c) indicate the number of independent replications of each experiment, if relevant Allocating animals to experimental groups 11 (a) Give full details of how animals were allocated to experimental groups, including randomization or matching if done; (b) describe the order in which the animals in the different experimental groups were treated and assessed Experimental outcomes 12 Clearly define the primary and secondary experimental outcomes assessed (e.g., cell death, molecular markers, behavioral changes) Statistical methods 13 (a) Provide details of the statistical methods used for each analysis; (b) specify the unit of analysis for each dataset (e.g., single animal, group of animals, single neuron); (c) describe any methods used to assess whether the data met the assumptions of the statistical approach...
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...…Flow & Metabolism (2011) 31, 991–993; doi:10.1038/jcbfm.2010.220; published online 5 January 2011 The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010)....
[...]
...Item Recommendation (Kilkenny et al, 2010) Title 1 Provide as accurate and concise a description of the content of the article as possible Abstract 2 Provide an accurate summary of the background, research objectives (including details of the species or strain of animal used), key methods, principal findings, and conclusions of the study...
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Journal Article•
1,345 citations
"Animal Research: Reporting in vivo ..." refers background in this paper
...…analysed 15 (a) Report the number of animals in each group included in each analysis; report absolute numbers (e.g., 10/20, not 50% (Schulz et al, 2010)); (b) if any animals or data were not included in the analysis, explain why Outcomes and estimation 16 Report the results for…...
[...]
...…study limitations, including any potential sources of bias, any limitations of the animal model, and the imprecision associated with the results (Schulz et al, 2010); (c) describe any implications of your experimental methods or findings for the replacement, refinement, or reduction (the 3Rs)…...
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