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A step-by-step guide to peer review: a template for patients and novice reviewers

1 General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Charlotte Blease

2 Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

3 Harvard Medical School

While relatively novel, patient peer review has the potential to change the healthcare publishing paradigm. It can do this by helping researchers enlarge the pool of people who are welcome to read, understand and participate in healthcare research. Academic journals who are early adopters of patient peer review have already committed to placing a priority on using person-centred language in publicly available abstracts and focusing on translational and practical research.

A wide body of literature has shown that including people with lived experiences in a truly meaningful way can improve the quality and efficiency of health research. Traditionally considered only as ‘subjects’ of research, over the last 10–15 years, patients and care partners have increasingly been invited to contribute to the design and conduct of studies. Established institutions are increasingly recognising the distinctive expertise patients possess—many patients have acquired deep insights about their conditions, symptoms, medical treatments and quality of healthcare delivery. Among some funders, including the views of patients is now a requirement to ensure research proposals are meaningful to persons with the lived experience of illness. Further illustrating these developments, patients are now involved in reviewing and making recommendations as part of funding institutions, setting research agendas and priorities, being funded for and leading their own research and leading or coauthoring scholarly publications, and are now participating in the peer review process for academic journals. 1–5 Patients offer an outsider’s perspective within mainstream healthcare: they have fewer institutional, professional or social allegiances and conflicts of interest—factors recognised as compromising the quality of research. Patient involvement is essential to move away from rhetorical commitments to embrace a truly patient-centred healthcare ecosystem where everyone has a place at the table.

As people with lived health experiences climb a ladder of engagement in patient–researcher partnerships, they may be asked to act as peer reviewers of academic manuscripts. However, many of these individuals do not hold professional training in medicine, healthcare or science and have never encountered the peer review process. Little guidance exists for patients and care partners tasked with reviewing and providing input on manuscripts in search of publication.

In conversation, however, even experienced researchers confess that learning how to peer review is part of a hidden curriculum in academia—a skill outlined by no formal means but rather learnt by mimicry. 6 As such, as they learn the process, novices may pick up bad habits. In the case of peer review, learning is the result of reading large numbers of academic papers, occasional conversations with mentors or commonly “trial by fire” experienced via reviewer comments to their own submissions. Patient reviewers are rarely exposed to these experiences and can be at a loss for where to begin. As a result, some may forgo opportunities to provide valuable and highly insightful feedback on research publications. Although some journals are highly specific about how reviewers should structure their feedback, many publications—including top-tier medical journals—assume that all reviewers will know how to construct responses. Only a few forward-thinking journals actively seeking peer review from people with lived health experiences currently point to review tips designed for experienced professionals. 7

As people with lived health experiences are increasingly invited to participate in peer review, it is essential that they be supported in this process. The peer review template for patients and novice reviewers ( table 1 ) is a series of steps designed to create a workflow for the main components of peer review. A structured workflow can help a reviewer organise their thoughts and create space to engage in critical thinking. The template is a starting point for anyone new to peer review, and it should be modified, adapted and built on for individual preferences and unique journal requirements. Peer reviews are commonly submitted via website portals, which vary widely in design and functionality; as such, reviewers are encouraged to decide how to best use the template on a case-by-case basis. Journals may require reviewers to copy and paste responses from the template into a journal website or upload a clean copy of the template as an attachment. Note: If uploading the review as an attachment, remember to remove the template examples and writing prompts .

Peer review template for patients and other novice reviewers

It is important to point out that patient reviewers are not alone in facing challenges and a steep learning curve in performing peer review. Many health research agendas and, as a result, publications straddle disciplines, requiring peer reviewers with complementary expertise and training. Some experts may be highly equipped to critique particular aspects of research papers while unsuited to comment on other parts. Curiously, however, it is seldom a requirement that invited peer reviewers admit their own limitations to comment on different dimensions of papers. Relatedly, while we do not suggest that all patient peer reviewers will be equipped to critique every aspect of submitted manuscripts—though some may be fully competent to do so—we suggest that candour about limitations of expertise would also benefit the broader research community.

As novice reviewers gain experience, they may find themselves solicited for a growing number of reviews, much like their more experienced counterparts or mentors. 8 Serving as a patient or care partner reviewer can be a rewarding form of advocacy and will be crucial to harnessing the feedback and expertise of persons with lived health experiences. As we move into a future where online searches for information are a ubiquitous first step in searching for answers to health-related questions, patient and novice reviewers may become the much-needed link between academia and the lay public.

Acknowledgments

LS thanks the experienced and novice reviewers who encouraged her to publish this template.

Twitter: @TheLizArmy, @@crblease

Contributors: Both authors contributed substantially to the manuscript. LS conceived the idea and design and drafted the text. CB refined the idea and critically revised the text.

Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests: The authors have read and understood the BMJ policy on declaration of interests and declare the following interests: LS is a member of the BMJ Patient Advisory Panel, serves as a BMJ patient reviewer and is an ad hoc patient reviewer for the Patient-Centered Outcomes Research Institute; CB is a Keane OpenNotes scholar; both LS and CB work on OpenNotes, a philanthropically funded research initiative focused on improving transparency in healthcare.

Provenance and peer review: Commissioned; externally peer reviewed.

Ethics statements

Patient consent for publication.

Not required.

How to Write a Peer Review: 12 things you need to know

peer review research paper template

Joanna Wilkinson

Learning how to peer review is no small feat. You’re responsible for protecting the public from false findings and research flaws, while at the same time helping to uncover legitimate breakthroughs. You’re also asked to constructively critique the research of your peers, some of which has taken blood, sweat, tears and years to put together.

Despite this, peer review doesn’t need to be hard or nerve-wracking–or make you feel like you’re doomed to fail.

We’ve put together  12 tips to help with peer review , and you can learn the entire process with our free peer review training course, the  Web of Science Academy . This on-demand, practical course and comes with one-to-one support with your own mentor. You’ll have exclusive access to our peer review template, plenty of expert review examples to learn from, and by the end of it, you’ll not only be a certified reviewer, we’ll help put you in front of editors in your field.

The peer review process

Journal peer review is a critical tool for ensuring the quality and integrity of the research literature. It is the process by which researchers use their expert knowledge of a topic to assess an article for its accuracy and rigor, and to help make sure it builds on and adds to the current literature.

It’s actually a very structured process; it can be learned and improved the more you do it, and you’ll become faster and more confident as time goes on. Soon enough, you’ll even start benefiting from the process yourself.

Peer review not only helps to maintain the quality and integrity of literature in your field, it’s key to your own development as a researcher. It’s a great way to keep abreast of current research, impress editors at elite journals, and hone your critical analysis skills. It teaches you how to  review a manuscript ,  spot common flaws in research papers , and improve your own chances of being a  successful published author .

12-step guide to writing a peer review

To get the most out of the peer review process, you’ll want to keep some best practice tips and techniques in mind from the start. This will help you write a review around two to three pages (four maximum) in length.

We asked an expert panel of researchers what steps they take to ensure a thorough and robust review. We then compiled their advice into 12 easy steps with link to blog posts for further information:

1)   Make sure you have the right expertise.  Check out our post,  Are you the right reviewer?  for our checklist to assess whether you should take on a certain peer review request.

2)   Visit the journal web page to learn their reviewer-specific instructions.  Check the manuscript fits in the journal format and the references are standardised (if the editor has not already done so).

3)   Skim the paper very quickly to get a general sense of the article.  Underline key words and arguments, and summarise key points. This will help you quickly “tune in” to the paper during the next read.

4)   Sit in a quiet place and read the manuscript critically.  Make sure you have the tables, figures and references visible. Ask yourself key questions, including: Does it have a relevant title and valuable research question? Are key papers referenced? What’s the author’s motivation for the study and the idea behind it? Are the data and tools suitable and correct? What’s new about it? Why does that matter? Are there other considerations? Find out more in our  12-step guide to critically reviewing a manuscript .

5)   Take notes about the major, moderate and minor revisions that need to be made . You need to make sure you can put the paper down and come back to it with fresh eyes later on. Note-taking is essential for this.

6)   Are there any methodological concerns or common research errors?  Check out our guide for  common research flaws to watch out for .

7)   Create a list of things to check.  For example, does the referenced study actually show what is claimed in the paper?

8)   Assess language and grammar, and make sure it’s a right ‘fit’ for the journal.  Does the paper flow? Does it have connectivity? Does it have clarity? Are the words and structure concise and effective?

9)   Is it new research?  Check previous publications of the authors and of other authors in the field to be sure that the results were not published before.

10)   Summarise your notes for the editor.  This can include overview, contribution, strengths & weaknesses, and acceptability. You can also include the manuscript’s contribution/context for the authors (really just to clarify whether you view it similarly, or not), then prioritise and collate the major revisions and minor/specific revisions into feedback. Try to compile this in a logical way, grouping similar things under a common heading where possible, and numbering them for ease of reference.

11)   Give specific recommendations to the authors for changes.  What do you want them to work on? in the manuscript that the authors can do.

12)  Give your recommendation to the editor.

We hope these 12 steps help get you on your way for your first peer review, or improving the structure of your current reviews. And remember, if you’d like to master the skills involved in peer review and get access to our Peer Review Template, sign up for our  Web of Science Academy .

Our expert panel of reviewers include:  Ana Marie Florea  (Heinrich-Heine-Universität Düsseldorf),  James Cotter  (University of Otago), and  Robert Faff  (University of Queensland). These reviewers are all recipients of the Global Peer Review Awards powered by Publons. They also and boast hundreds of pre-publication peer reviews for more than 100 different journals and sit on numerous editorial boards.

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Page Content

Overview of the review report format, the first read-through, first read considerations, spotting potential major flaws, concluding the first reading, rejection after the first reading, before starting the second read-through, doing the second read-through, the second read-through: section by section guidance, how to structure your report, on presentation and style, criticisms & confidential comments to editors, the recommendation, when recommending rejection, additional resources, step by step guide to reviewing a manuscript.

When you receive an invitation to peer review, you should be sent a copy of the paper's abstract to help you decide whether you wish to do the review. Try to respond to invitations promptly - it will prevent delays. It is also important at this stage to declare any potential Conflict of Interest.

The structure of the review report varies between journals. Some follow an informal structure, while others have a more formal approach.

" Number your comments!!! " (Jonathon Halbesleben, former Editor of Journal of Occupational and Organizational Psychology)

Informal Structure

Many journals don't provide criteria for reviews beyond asking for your 'analysis of merits'. In this case, you may wish to familiarize yourself with examples of other reviews done for the journal, which the editor should be able to provide or, as you gain experience, rely on your own evolving style.

Formal Structure

Other journals require a more formal approach. Sometimes they will ask you to address specific questions in your review via a questionnaire. Or they might want you to rate the manuscript on various attributes using a scorecard. Often you can't see these until you log in to submit your review. So when you agree to the work, it's worth checking for any journal-specific guidelines and requirements. If there are formal guidelines, let them direct the structure of your review.

In Both Cases

Whether specifically required by the reporting format or not, you should expect to compile comments to authors and possibly confidential ones to editors only.

Reviewing with Empathy

Following the invitation to review, when you'll have received the article abstract, you should already understand the aims, key data and conclusions of the manuscript. If you don't, make a note now that you need to feedback on how to improve those sections.

The first read-through is a skim-read. It will help you form an initial impression of the paper and get a sense of whether your eventual recommendation will be to accept or reject the paper.

Keep a pen and paper handy when skim-reading.

Try to bear in mind the following questions - they'll help you form your overall impression:

  • What is the main question addressed by the research? Is it relevant and interesting?
  • How original is the topic? What does it add to the subject area compared with other published material?
  • Is the paper well written? Is the text clear and easy to read?
  • Are the conclusions consistent with the evidence and arguments presented? Do they address the main question posed?
  • If the author is disagreeing significantly with the current academic consensus, do they have a substantial case? If not, what would be required to make their case credible?
  • If the paper includes tables or figures, what do they add to the paper? Do they aid understanding or are they superfluous?

While you should read the whole paper, making the right choice of what to read first can save time by flagging major problems early on.

Editors say, " Specific recommendations for remedying flaws are VERY welcome ."

Examples of possibly major flaws include:

  • Drawing a conclusion that is contradicted by the author's own statistical or qualitative evidence
  • The use of a discredited method
  • Ignoring a process that is known to have a strong influence on the area under study

If experimental design features prominently in the paper, first check that the methodology is sound - if not, this is likely to be a major flaw.

You might examine:

  • The sampling in analytical papers
  • The sufficient use of control experiments
  • The precision of process data
  • The regularity of sampling in time-dependent studies
  • The validity of questions, the use of a detailed methodology and the data analysis being done systematically (in qualitative research)
  • That qualitative research extends beyond the author's opinions, with sufficient descriptive elements and appropriate quotes from interviews or focus groups

Major Flaws in Information

If methodology is less of an issue, it's often a good idea to look at the data tables, figures or images first. Especially in science research, it's all about the information gathered. If there are critical flaws in this, it's very likely the manuscript will need to be rejected. Such issues include:

  • Insufficient data
  • Unclear data tables
  • Contradictory data that either are not self-consistent or disagree with the conclusions
  • Confirmatory data that adds little, if anything, to current understanding - unless strong arguments for such repetition are made

If you find a major problem, note your reasoning and clear supporting evidence (including citations).

After the initial read and using your notes, including those of any major flaws you found, draft the first two paragraphs of your review - the first summarizing the research question addressed and the second the contribution of the work. If the journal has a prescribed reporting format, this draft will still help you compose your thoughts.

The First Paragraph

This should state the main question addressed by the research and summarize the goals, approaches, and conclusions of the paper. It should:

  • Help the editor properly contextualize the research and add weight to your judgement
  • Show the author what key messages are conveyed to the reader, so they can be sure they are achieving what they set out to do
  • Focus on successful aspects of the paper so the author gets a sense of what they've done well

The Second Paragraph

This should provide a conceptual overview of the contribution of the research. So consider:

  • Is the paper's premise interesting and important?
  • Are the methods used appropriate?
  • Do the data support the conclusions?

After drafting these two paragraphs, you should be in a position to decide whether this manuscript is seriously flawed and should be rejected (see the next section). Or whether it is publishable in principle and merits a detailed, careful read through.

Even if you are coming to the opinion that an article has serious flaws, make sure you read the whole paper. This is very important because you may find some really positive aspects that can be communicated to the author. This could help them with future submissions.

A full read-through will also make sure that any initial concerns are indeed correct and fair. After all, you need the context of the whole paper before deciding to reject. If you still intend to recommend rejection, see the section "When recommending rejection."

Once the paper has passed your first read and you've decided the article is publishable in principle, one purpose of the second, detailed read-through is to help prepare the manuscript for publication. You may still decide to recommend rejection following a second reading.

" Offer clear suggestions for how the authors can address the concerns raised. In other words, if you're going to raise a problem, provide a solution ." (Jonathon Halbesleben, Editor of Journal of Occupational and Organizational Psychology)

Preparation

To save time and simplify the review:

  • Don't rely solely upon inserting comments on the manuscript document - make separate notes
  • Try to group similar concerns or praise together
  • If using a review program to note directly onto the manuscript, still try grouping the concerns and praise in separate notes - it helps later
  • Note line numbers of text upon which your notes are based - this helps you find items again and also aids those reading your review

Now that you have completed your preparations, you're ready to spend an hour or so reading carefully through the manuscript.

As you're reading through the manuscript for a second time, you'll need to keep in mind the argument's construction, the clarity of the language and content.

With regard to the argument’s construction, you should identify:

  • Any places where the meaning is unclear or ambiguous
  • Any factual errors
  • Any invalid arguments

You may also wish to consider:

  • Does the title properly reflect the subject of the paper?
  • Does the abstract provide an accessible summary of the paper?
  • Do the keywords accurately reflect the content?
  • Is the paper an appropriate length?
  • Are the key messages short, accurate and clear?

Not every submission is well written. Part of your role is to make sure that the text’s meaning is clear.

Editors say, " If a manuscript has many English language and editing issues, please do not try and fix it. If it is too bad, note that in your review and it should be up to the authors to have the manuscript edited ."

If the article is difficult to understand, you should have rejected it already. However, if the language is poor but you understand the core message, see if you can suggest improvements to fix the problem:

  • Are there certain aspects that could be communicated better, such as parts of the discussion?
  • Should the authors consider resubmitting to the same journal after language improvements?
  • Would you consider looking at the paper again once these issues are dealt with?

On Grammar and Punctuation

Your primary role is judging the research content. Don't spend time polishing grammar or spelling. Editors will make sure that the text is at a high standard before publication. However, if you spot grammatical errors that affect clarity of meaning, then it's important to highlight these. Expect to suggest such amendments - it's rare for a manuscript to pass review with no corrections.

A 2010 study of nursing journals found that 79% of recommendations by reviewers were influenced by grammar and writing style (Shattel, et al., 2010).

1. The Introduction

A well-written introduction:

  • Sets out the argument
  • Summarizes recent research related to the topic
  • Highlights gaps in current understanding or conflicts in current knowledge
  • Establishes the originality of the research aims by demonstrating the need for investigations in the topic area
  • Gives a clear idea of the target readership, why the research was carried out and the novelty and topicality of the manuscript

Originality and Topicality

Originality and topicality can only be established in the light of recent authoritative research. For example, it's impossible to argue that there is a conflict in current understanding by referencing articles that are 10 years old.

Authors may make the case that a topic hasn't been investigated in several years and that new research is required. This point is only valid if researchers can point to recent developments in data gathering techniques or to research in indirectly related fields that suggest the topic needs revisiting. Clearly, authors can only do this by referencing recent literature. Obviously, where older research is seminal or where aspects of the methodology rely upon it, then it is perfectly appropriate for authors to cite some older papers.

Editors say, "Is the report providing new information; is it novel or just confirmatory of well-known outcomes ?"

It's common for the introduction to end by stating the research aims. By this point you should already have a good impression of them - if the explicit aims come as a surprise, then the introduction needs improvement.

2. Materials and Methods

Academic research should be replicable, repeatable and robust - and follow best practice.

Replicable Research

This makes sufficient use of:

  • Control experiments
  • Repeated analyses
  • Repeated experiments

These are used to make sure observed trends are not due to chance and that the same experiment could be repeated by other researchers - and result in the same outcome. Statistical analyses will not be sound if methods are not replicable. Where research is not replicable, the paper should be recommended for rejection.

Repeatable Methods

These give enough detail so that other researchers are able to carry out the same research. For example, equipment used or sampling methods should all be described in detail so that others could follow the same steps. Where methods are not detailed enough, it's usual to ask for the methods section to be revised.

Robust Research

This has enough data points to make sure the data are reliable. If there are insufficient data, it might be appropriate to recommend revision. You should also consider whether there is any in-built bias not nullified by the control experiments.

Best Practice

During these checks you should keep in mind best practice:

  • Standard guidelines were followed (e.g. the CONSORT Statement for reporting randomized trials)
  • The health and safety of all participants in the study was not compromised
  • Ethical standards were maintained

If the research fails to reach relevant best practice standards, it's usual to recommend rejection. What's more, you don't then need to read any further.

3. Results and Discussion

This section should tell a coherent story - What happened? What was discovered or confirmed?

Certain patterns of good reporting need to be followed by the author:

  • They should start by describing in simple terms what the data show
  • They should make reference to statistical analyses, such as significance or goodness of fit
  • Once described, they should evaluate the trends observed and explain the significance of the results to wider understanding. This can only be done by referencing published research
  • The outcome should be a critical analysis of the data collected

Discussion should always, at some point, gather all the information together into a single whole. Authors should describe and discuss the overall story formed. If there are gaps or inconsistencies in the story, they should address these and suggest ways future research might confirm the findings or take the research forward.

4. Conclusions

This section is usually no more than a few paragraphs and may be presented as part of the results and discussion, or in a separate section. The conclusions should reflect upon the aims - whether they were achieved or not - and, just like the aims, should not be surprising. If the conclusions are not evidence-based, it's appropriate to ask for them to be re-written.

5. Information Gathered: Images, Graphs and Data Tables

If you find yourself looking at a piece of information from which you cannot discern a story, then you should ask for improvements in presentation. This could be an issue with titles, labels, statistical notation or image quality.

Where information is clear, you should check that:

  • The results seem plausible, in case there is an error in data gathering
  • The trends you can see support the paper's discussion and conclusions
  • There are sufficient data. For example, in studies carried out over time are there sufficient data points to support the trends described by the author?

You should also check whether images have been edited or manipulated to emphasize the story they tell. This may be appropriate but only if authors report on how the image has been edited (e.g. by highlighting certain parts of an image). Where you feel that an image has been edited or manipulated without explanation, you should highlight this in a confidential comment to the editor in your report.

6. List of References

You will need to check referencing for accuracy, adequacy and balance.

Where a cited article is central to the author's argument, you should check the accuracy and format of the reference - and bear in mind different subject areas may use citations differently. Otherwise, it's the editor’s role to exhaustively check the reference section for accuracy and format.

You should consider if the referencing is adequate:

  • Are important parts of the argument poorly supported?
  • Are there published studies that show similar or dissimilar trends that should be discussed?
  • If a manuscript only uses half the citations typical in its field, this may be an indicator that referencing should be improved - but don't be guided solely by quantity
  • References should be relevant, recent and readily retrievable

Check for a well-balanced list of references that is:

  • Helpful to the reader
  • Fair to competing authors
  • Not over-reliant on self-citation
  • Gives due recognition to the initial discoveries and related work that led to the work under assessment

You should be able to evaluate whether the article meets the criteria for balanced referencing without looking up every reference.

7. Plagiarism

By now you will have a deep understanding of the paper's content - and you may have some concerns about plagiarism.

Identified Concern

If you find - or already knew of - a very similar paper, this may be because the author overlooked it in their own literature search. Or it may be because it is very recent or published in a journal slightly outside their usual field.

You may feel you can advise the author how to emphasize the novel aspects of their own study, so as to better differentiate it from similar research. If so, you may ask the author to discuss their aims and results, or modify their conclusions, in light of the similar article. Of course, the research similarities may be so great that they render the work unoriginal and you have no choice but to recommend rejection.

"It's very helpful when a reviewer can point out recent similar publications on the same topic by other groups, or that the authors have already published some data elsewhere ." (Editor feedback)

Suspected Concern

If you suspect plagiarism, including self-plagiarism, but cannot recall or locate exactly what is being plagiarized, notify the editor of your suspicion and ask for guidance.

Most editors have access to software that can check for plagiarism.

Editors are not out to police every paper, but when plagiarism is discovered during peer review it can be properly addressed ahead of publication. If plagiarism is discovered only after publication, the consequences are worse for both authors and readers, because a retraction may be necessary.

For detailed guidelines see COPE's Ethical guidelines for reviewers and Wiley's Best Practice Guidelines on Publishing Ethics .

8. Search Engine Optimization (SEO)

After the detailed read-through, you will be in a position to advise whether the title, abstract and key words are optimized for search purposes. In order to be effective, good SEO terms will reflect the aims of the research.

A clear title and abstract will improve the paper's search engine rankings and will influence whether the user finds and then decides to navigate to the main article. The title should contain the relevant SEO terms early on. This has a major effect on the impact of a paper, since it helps it appear in search results. A poor abstract can then lose the reader's interest and undo the benefit of an effective title - whilst the paper's abstract may appear in search results, the potential reader may go no further.

So ask yourself, while the abstract may have seemed adequate during earlier checks, does it:

  • Do justice to the manuscript in this context?
  • Highlight important findings sufficiently?
  • Present the most interesting data?

Editors say, " Does the Abstract highlight the important findings of the study ?"

If there is a formal report format, remember to follow it. This will often comprise a range of questions followed by comment sections. Try to answer all the questions. They are there because the editor felt that they are important. If you're following an informal report format you could structure your report in three sections: summary, major issues, minor issues.

  • Give positive feedback first. Authors are more likely to read your review if you do so. But don't overdo it if you will be recommending rejection
  • Briefly summarize what the paper is about and what the findings are
  • Try to put the findings of the paper into the context of the existing literature and current knowledge
  • Indicate the significance of the work and if it is novel or mainly confirmatory
  • Indicate the work's strengths, its quality and completeness
  • State any major flaws or weaknesses and note any special considerations. For example, if previously held theories are being overlooked

Major Issues

  • Are there any major flaws? State what they are and what the severity of their impact is on the paper
  • Has similar work already been published without the authors acknowledging this?
  • Are the authors presenting findings that challenge current thinking? Is the evidence they present strong enough to prove their case? Have they cited all the relevant work that would contradict their thinking and addressed it appropriately?
  • If major revisions are required, try to indicate clearly what they are
  • Are there any major presentational problems? Are figures & tables, language and manuscript structure all clear enough for you to accurately assess the work?
  • Are there any ethical issues? If you are unsure it may be better to disclose these in the confidential comments section

Minor Issues

  • Are there places where meaning is ambiguous? How can this be corrected?
  • Are the correct references cited? If not, which should be cited instead/also? Are citations excessive, limited, or biased?
  • Are there any factual, numerical or unit errors? If so, what are they?
  • Are all tables and figures appropriate, sufficient, and correctly labelled? If not, say which are not

Your review should ultimately help the author improve their article. So be polite, honest and clear. You should also try to be objective and constructive, not subjective and destructive.

You should also:

  • Write clearly and so you can be understood by people whose first language is not English
  • Avoid complex or unusual words, especially ones that would even confuse native speakers
  • Number your points and refer to page and line numbers in the manuscript when making specific comments
  • If you have been asked to only comment on specific parts or aspects of the manuscript, you should indicate clearly which these are
  • Treat the author's work the way you would like your own to be treated

Most journals give reviewers the option to provide some confidential comments to editors. Often this is where editors will want reviewers to state their recommendation - see the next section - but otherwise this area is best reserved for communicating malpractice such as suspected plagiarism, fraud, unattributed work, unethical procedures, duplicate publication, bias or other conflicts of interest.

However, this doesn't give reviewers permission to 'backstab' the author. Authors can't see this feedback and are unable to give their side of the story unless the editor asks them to. So in the spirit of fairness, write comments to editors as though authors might read them too.

Reviewers should check the preferences of individual journals as to where they want review decisions to be stated. In particular, bear in mind that some journals will not want the recommendation included in any comments to authors, as this can cause editors difficulty later - see Section 11 for more advice about working with editors.

You will normally be asked to indicate your recommendation (e.g. accept, reject, revise and resubmit, etc.) from a fixed-choice list and then to enter your comments into a separate text box.

Recommending Acceptance

If you're recommending acceptance, give details outlining why, and if there are any areas that could be improved. Don't just give a short, cursory remark such as 'great, accept'. See Improving the Manuscript

Recommending Revision

Where improvements are needed, a recommendation for major or minor revision is typical. You may also choose to state whether you opt in or out of the post-revision review too. If recommending revision, state specific changes you feel need to be made. The author can then reply to each point in turn.

Some journals offer the option to recommend rejection with the possibility of resubmission – this is most relevant where substantial, major revision is necessary.

What can reviewers do to help? " Be clear in their comments to the author (or editor) which points are absolutely critical if the paper is given an opportunity for revisio n." (Jonathon Halbesleben, Editor of Journal of Occupational and Organizational Psychology)

Recommending Rejection

If recommending rejection or major revision, state this clearly in your review (and see the next section, 'When recommending rejection').

Where manuscripts have serious flaws you should not spend any time polishing the review you've drafted or give detailed advice on presentation.

Editors say, " If a reviewer suggests a rejection, but her/his comments are not detailed or helpful, it does not help the editor in making a decision ."

In your recommendations for the author, you should:

  • Give constructive feedback describing ways that they could improve the research
  • Keep the focus on the research and not the author. This is an extremely important part of your job as a reviewer
  • Avoid making critical confidential comments to the editor while being polite and encouraging to the author - the latter may not understand why their manuscript has been rejected. Also, they won't get feedback on how to improve their research and it could trigger an appeal

Remember to give constructive criticism even if recommending rejection. This helps developing researchers improve their work and explains to the editor why you felt the manuscript should not be published.

" When the comments seem really positive, but the recommendation is rejection…it puts the editor in a tough position of having to reject a paper when the comments make it sound like a great paper ." (Jonathon Halbesleben, Editor of Journal of Occupational and Organizational Psychology)

Visit our Wiley Author Learning and Training Channel for expert advice on peer review.

Watch the video, Ethical considerations of Peer Review

The Savvy Scientist

The Savvy Scientist

Experiences of a London PhD student and beyond

My Complete Guide to Academic Peer Review: Example Comments & How to Make Paper Revisions

peer review research paper template

Once you’ve submitted your paper to an academic journal you’re in the nerve-racking position of waiting to hear back about the fate of your work. In this post we’ll cover everything from potential responses you could receive from the editor and example peer review comments through to how to submit revisions.

My first first-author paper was reviewed by five (yes 5!) reviewers and since then I’ve published several others papers, so now I want to share the insights I’ve gained which will hopefully help you out!

This post is part of my series to help with writing and publishing your first academic journal paper. You can find the whole series here: Writing an academic journal paper .

The Peer Review Process

An overview of the academic journal peer review process.

When you submit a paper to a journal, the first thing that will happen is one of the editorial team will do an initial assessment of whether or not the article is of interest. They may decide for a number of reasons that the article isn’t suitable for the journal and may reject the submission before even sending it out to reviewers.

If this happens hopefully they’ll have let you know quickly so that you can move on and make a start targeting a different journal instead.

Handy way to check the status – Sign in to the journal’s submission website and have a look at the status of your journal article online. If you can see that the article is under review then you’ve passed that first hurdle!

When your paper is under peer review, the journal will have set out a framework to help the reviewers assess your work. Generally they’ll be deciding whether the work is to a high enough standard.

Interested in reading about what reviewers are looking for? Check out my post on being a reviewer for the first time. Peer-Reviewing Journal Articles: Should You Do It? Sharing What I Learned From My First Experiences .

Once the reviewers have made their assessments, they’ll return their comments and suggestions to the editor who will then decide how the article should proceed.

How Many People Review Each Paper?

The editor ideally wants a clear decision from the reviewers as to whether the paper should be accepted or rejected. If there is no consensus among the reviewers then the editor may send your paper out to more reviewers to better judge whether or not to accept the paper.

If you’ve got a lot of reviewers on your paper it isn’t necessarily that the reviewers disagreed about accepting your paper.

You can also end up with lots of reviewers in the following circumstance:

  • The editor asks a certain academic to review the paper but doesn’t get a response from them
  • The editor asks another academic to step in
  • The initial reviewer then responds

Next thing you know your work is being scrutinised by extra pairs of eyes!

As mentioned in the intro, my first paper ended up with five reviewers!

Potential Journal Responses

Assuming that the paper passes the editor’s initial evaluation and is sent out for peer-review, here are the potential decisions you may receive:

  • Reject the paper. Sadly the editor and reviewers decided against publishing your work. Hopefully they’ll have included feedback which you can incorporate into your submission to another journal. I’ve had some rejections and the reviewer comments were genuinely useful.
  • Accept the paper with major revisions . Good news: with some more work your paper could get published. If you make all the changes that the reviewers suggest, and they’re happy with your responses, then it should get accepted. Some people see major revisions as a disappointment but it doesn’t have to be.
  • Accept the paper with minor revisions. This is like getting a major revisions response but better! Generally minor revisions can be addressed quickly and often come down to clarifying things for the reviewers: rewording, addressing minor concerns etc and don’t require any more experiments or analysis. You stand a really good chance of getting the paper published if you’ve been given a minor revisions result.
  • Accept the paper with no revisions . I’m not sure that this ever really happens, but it is potentially possible if the reviewers are already completely happy with your paper!

Keen to know more about academic publishing? My series on publishing is now available as a free eBook. It includes my experiences being a peer reviewer. Click the image below for access.

peer review research paper template

Example Peer Review Comments & Addressing Reviewer Feedback

If your paper has been accepted but requires revisions, the editor will forward to you the comments and concerns that the reviewers raised. You’ll have to address these points so that the reviewers are satisfied your work is of a publishable standard.

It is extremely important to take this stage seriously. If you don’t do a thorough job then the reviewers won’t recommend that your paper is accepted for publication!

You’ll have to put together a resubmission with your co-authors and there are two crucial things you must do:

  • Make revisions to your manuscript based off reviewer comments
  • Reply to the reviewers, telling them the changes you’ve made and potentially changes you’ve not made in instances where you disagree with them. Read on to see some example peer review comments and how I replied!

Before making any changes to your actual paper, I suggest having a thorough read through the reviewer comments.

Once you’ve read through the comments you might be keen to dive straight in and make the changes in your paper. Instead, I actually suggest firstly drafting your reply to the reviewers.

Why start with the reply to reviewers? Well in a way it is actually potentially more important than the changes you’re making in the manuscript.

Imagine when a reviewer receives your response to their comments: you want them to be able to read your reply document and be satisfied that their queries have largely been addressed without even having to open the updated draft of your manuscript. If you do a good job with the replies, the reviewers will be better placed to recommend the paper be accepted!

By starting with your reply to the reviewers you’ll also clarify for yourself what changes actually have to be made to the paper.

So let’s now cover how to reply to the reviewers.

1. Replying to Journal Reviewers

It is so important to make sure you do a solid job addressing your reviewers’ feedback in your reply document. If you leave anything unanswered you’re asking for trouble, which in this case means either a rejection or another round of revisions: though some journals only give you one shot! Therefore make sure you’re thorough, not just with making the changes but demonstrating the changes in your replies.

It’s no good putting in the work to revise your paper but not evidence it in your reply to the reviewers!

There may be points that reviewers raise which don’t appear to necessitate making changes to your manuscript, but this is rarely the case. Even for comments or concerns they raise which are already addressed in the paper, clearly those areas could be clarified or highlighted to ensure that future readers don’t get confused.

How to Reply to Journal Reviewers

Some journals will request a certain format for how you should structure a reply to the reviewers. If so this should be included in the email you receive from the journal’s editor. If there are no certain requirements here is what I do:

  • Copy and paste all replies into a document.
  • Separate out each point they raise onto a separate line. Often they’ll already be nicely numbered but sometimes they actually still raise separate issues in one block of text. I suggest separating it all out so that each query is addressed separately.
  • Form your reply for each point that they raise. I start by just jotting down notes for roughly how I’ll respond. Once I’m happy with the key message I’ll write it up into a scripted reply.
  • Finally, go through and format it nicely and include line number references for the changes you’ve made in the manuscript.

By the end you’ll have a document that looks something like:

Reviewer 1 Point 1: [Quote the reviewer’s comment] Response 1: [Address point 1 and say what revisions you’ve made to the paper] Point 2: [Quote the reviewer’s comment] Response 2: [Address point 2 and say what revisions you’ve made to the paper] Then repeat this for all comments by all reviewers!

What To Actually Include In Your Reply To Reviewers

For every single point raised by the reviewers, you should do the following:

  • Address their concern: Do you agree or disagree with the reviewer’s comment? Either way, make your position clear and justify any differences of opinion. If the reviewer wants more clarity on an issue, provide it. It is really important that you actually address their concerns in your reply. Don’t just say “Thanks, we’ve changed the text”. Actually include everything they want to know in your reply. Yes this means you’ll be repeating things between your reply and the revisions to the paper but that’s fine.
  • Reference changes to your manuscript in your reply. Once you’ve answered the reviewer’s question, you must show that you’re actually using this feedback to revise the manuscript. The best way to do this is to refer to where the changes have been made throughout the text. I personally do this by include line references. Make sure you save this right until the end once you’ve finished making changes!

Example Peer Review Comments & Author Replies

In order to understand how this works in practice I’d suggest reading through a few real-life example peer review comments and replies.

The good news is that published papers often now include peer-review records, including the reviewer comments and authors’ replies. So here are two feedback examples from my own papers:

Example Peer Review: Paper 1

Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine, J. Clark et al. 2020 – Available here

This paper was reviewed by two academics and was given major revisions. The journal gave us only 10 days to get them done, which was a bit stressful!

  • Reviewer Comments
  • My reply to Reviewer 1
  • My reply to Reviewer 2

One round of reviews wasn’t enough for Reviewer 2…

  • My reply to Reviewer 2 – ROUND 2

Thankfully it was accepted after the second round of review, and actually ended up being selected for this accolade, whatever most notable means?!

Nice to see our recent paper highlighted as one of the most notable articles, great start to the week! Thanks @Materials_mdpi 😀 #openaccess & available here: https://t.co/AKWLcyUtpC @ICBiomechanics @julianrjones @saman_tavana pic.twitter.com/ciOX2vftVL — Jeff Clark (@savvy_scientist) December 7, 2020

Example Peer Review: Paper 2

Exploratory Full-Field Mechanical Analysis across the Osteochondral Tissue—Biomaterial Interface in an Ovine Model, J. Clark et al. 2020 – Available here

This paper was reviewed by three academics and was given minor revisions.

  • My reply to Reviewer 3

I’m pleased to say it was accepted after the first round of revisions 🙂

Things To Be Aware Of When Replying To Peer Review Comments

  • Generally, try to make a revision to your paper for every comment. No matter what the reviewer’s comment is, you can probably make a change to the paper which will improve your manuscript. For example, if the reviewer seems confused about something, improve the clarity in your paper. If you disagree with the reviewer, include better justification for your choices in the paper. It is far more favourable to take on board the reviewer’s feedback and act on it with actual changes to your draft.
  • Organise your responses. Sometimes journals will request the reply to each reviewer is sent in a separate document. Unless they ask for it this way I stick them all together in one document with subheadings eg “Reviewer 1” etc.
  • Make sure you address each and every question. If you dodge anything then the reviewer will have a valid reason to reject your resubmission. You don’t need to agree with them on every point but you do need to justify your position.
  • Be courteous. No need to go overboard with compliments but stay polite as reviewers are providing constructive feedback. I like to add in “We thank the reviewer for their suggestion” every so often where it genuinely warrants it. Remember that written language doesn’t always carry tone very well, so rather than risk coming off as abrasive if I don’t agree with the reviewer’s suggestion I’d rather be generous with friendliness throughout the reply.

2. How to Make Revisions To Your Paper

Once you’ve drafted your replies to the reviewers, you’ve actually done a lot of the ground work for making changes to the paper. Remember, you are making changes to the paper based off the reviewer comments so you should regularly be referring back to the comments to ensure you’re not getting sidetracked.

Reviewers could request modifications to any part of your paper. You may need to collect more data, do more analysis, reformat some figures, add in more references or discussion or any number of other revisions! So I can’t really help with everything, even so here is some general advice:

  • Use tracked-changes. This is so important. The editor and reviewers need to be able to see every single change you’ve made compared to your first submission. Sometimes the journal will want a clean copy too but always start with tracked-changes enabled then just save a clean copy afterwards.
  • Be thorough . Try to not leave any opportunity for the reviewers to not recommend your paper to be published. Any chance you have to satisfy their concerns, take it. For example if the reviewers are concerned about sample size and you have the means to include other experiments, consider doing so. If they want to see more justification or references, be thorough. To be clear again, this doesn’t necessarily mean making changes you don’t believe in. If you don’t want to make a change, you can justify your position to the reviewers. Either way, be thorough.
  • Use your reply to the reviewers as a guide. In your draft reply to the reviewers you should have already included a lot of details which can be incorporated into the text. If they raised a concern, you should be able to go and find references which address the concern. This reference should appear both in your reply and in the manuscript. As mentioned above I always suggest starting with the reply, then simply adding these details to your manuscript once you know what needs doing.

Putting Together Your Paper Revision Submission

  • Once you’ve drafted your reply to the reviewers and revised manuscript, make sure to give sufficient time for your co-authors to give feedback. Also give yourself time afterwards to make changes based off of their feedback. I ideally give a week for the feedback and another few days to make the changes.
  • When you’re satisfied that you’ve addressed the reviewer comments, you can think about submitting it. The journal may ask for another letter to the editor, if not I simply add to the top of the reply to reviewers something like:
“Dear [Editor], We are grateful to the reviewer for their positive and constructive comments that have led to an improved manuscript.  Here, we address their concerns/suggestions and have tracked changes throughout the revised manuscript.”

Once you’re ready to submit:

  • Double check that you’ve done everything that the editor requested in their email
  • Double check that the file names and formats are as required
  • Triple check you’ve addressed the reviewer comments adequately
  • Click submit and bask in relief!

You won’t always get the paper accepted, but if you’re thorough and present your revisions clearly then you’ll put yourself in a really good position. Remember to try as hard as possible to satisfy the reviewers’ concerns to minimise any opportunity for them to not accept your revisions!

Best of luck!

I really hope that this post has been useful to you and that the example peer review section has given you some ideas for how to respond. I know how daunting it can be to reply to reviewers, and it is really important to try to do a good job and give yourself the best chances of success. If you’d like to read other posts in my academic publishing series you can find them here:

Blog post series: Writing an academic journal paper

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2 Comments on “My Complete Guide to Academic Peer Review: Example Comments & How to Make Paper Revisions”

Excellent article! Thank you for the inspiration!

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  • Volume 28, Issue 1
  • A step-by-step guide to peer review: a template for patients and novice reviewers
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  • http://orcid.org/0000-0003-3798-7438 Liz Salmi 1 and
  • http://orcid.org/0000-0002-0205-1165 Charlotte Blease 2 , 3
  • 1 General Medicine and Primary Care , Beth Israel Deaconess Medical Center , Boston , Massachusetts , USA
  • 2 Beth Israel Deaconess Medical Center , Boston , Massachusetts , USA
  • 3 Harvard Medical School
  • Correspondence to Ms Liz Salmi; lsalmi{at}bidmc.harvard.edu

https://doi.org/10.1136/bmjhci-2021-100392

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  • patient-centred care
  • BMJ health informatics
  • consumer health informatics
  • health communication
  • health literacy

While relatively novel, patient peer review has the potential to change the healthcare publishing paradigm. It can do this by helping researchers enlarge the pool of people who are welcome to read, understand and participate in healthcare research. Academic journals who are early adopters of patient peer review have already committed to placing a priority on using person-centred language in publicly available abstracts and focusing on translational and practical research.

A wide body of literature has shown that including people with lived experiences in a truly meaningful way can improve the quality and efficiency of health research. Traditionally considered only as ‘subjects’ of research, over the last 10–15 years, patients and care partners have increasingly been invited to contribute to the design and conduct of studies. Established institutions are increasingly recognising the distinctive expertise patients possess—many patients have acquired deep insights about their conditions, symptoms, medical treatments and quality of healthcare delivery. Among some funders, including the views of patients is now a requirement to ensure research proposals are meaningful to persons with the lived experience of illness. Further illustrating these developments, patients are now involved in reviewing and making recommendations as part of funding institutions, setting research agendas and priorities, being funded for and leading their own research and leading or coauthoring scholarly publications, and are now participating in the peer review process for academic journals. 1–5 Patients offer an outsider’s perspective within mainstream healthcare: they have fewer institutional, professional or social allegiances and conflicts of interest—factors recognised as compromising the quality of research. Patient involvement is essential to move away from rhetorical commitments to embrace a truly patient-centred healthcare ecosystem where everyone has a place at the table.

As people with lived health experiences climb a ladder of engagement in patient–researcher partnerships, they may be asked to act as peer reviewers of academic manuscripts. However, many of these individuals do not hold professional training in medicine, healthcare or science and have never encountered the peer review process. Little guidance exists for patients and care partners tasked with reviewing and providing input on manuscripts in search of publication.

In conversation, however, even experienced researchers confess that learning how to peer review is part of a hidden curriculum in academia—a skill outlined by no formal means but rather learnt by mimicry. 6 As such, as they learn the process, novices may pick up bad habits. In the case of peer review, learning is the result of reading large numbers of academic papers, occasional conversations with mentors or commonly “trial by fire” experienced via reviewer comments to their own submissions. Patient reviewers are rarely exposed to these experiences and can be at a loss for where to begin. As a result, some may forgo opportunities to provide valuable and highly insightful feedback on research publications. Although some journals are highly specific about how reviewers should structure their feedback, many publications—including top-tier medical journals—assume that all reviewers will know how to construct responses. Only a few forward-thinking journals actively seeking peer review from people with lived health experiences currently point to review tips designed for experienced professionals. 7

As people with lived health experiences are increasingly invited to participate in peer review, it is essential that they be supported in this process. The peer review template for patients and novice reviewers ( table 1 ) is a series of steps designed to create a workflow for the main components of peer review. A structured workflow can help a reviewer organise their thoughts and create space to engage in critical thinking. The template is a starting point for anyone new to peer review, and it should be modified, adapted and built on for individual preferences and unique journal requirements. Peer reviews are commonly submitted via website portals, which vary widely in design and functionality; as such, reviewers are encouraged to decide how to best use the template on a case-by-case basis. Journals may require reviewers to copy and paste responses from the template into a journal website or upload a clean copy of the template as an attachment. Note: If uploading the review as an attachment, remember to remove the template examples and writing prompts .

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Peer review template for patients and other novice reviewers

It is important to point out that patient reviewers are not alone in facing challenges and a steep learning curve in performing peer review. Many health research agendas and, as a result, publications straddle disciplines, requiring peer reviewers with complementary expertise and training. Some experts may be highly equipped to critique particular aspects of research papers while unsuited to comment on other parts. Curiously, however, it is seldom a requirement that invited peer reviewers admit their own limitations to comment on different dimensions of papers. Relatedly, while we do not suggest that all patient peer reviewers will be equipped to critique every aspect of submitted manuscripts—though some may be fully competent to do so—we suggest that candour about limitations of expertise would also benefit the broader research community.

As novice reviewers gain experience, they may find themselves solicited for a growing number of reviews, much like their more experienced counterparts or mentors. 8 Serving as a patient or care partner reviewer can be a rewarding form of advocacy and will be crucial to harnessing the feedback and expertise of persons with lived health experiences. As we move into a future where online searches for information are a ubiquitous first step in searching for answers to health-related questions, patient and novice reviewers may become the much-needed link between academia and the lay public.

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Acknowledgments

  • Engage with Us
  • ↵ Coordinating Center for Clinical Trials - Patient Advocate Steering Committee [Internet]. National Cancer Institute. U.S. Department of Health and Human Services. National Institute of Health . Available: https://www.cancer.gov/about-nci/organization/ccct/steering-committees/patient-advocate [Accessed 16 Apr 2021 ].
  • ↵ Transforming Healthcare through Innovative and Impactful Research [Internet]. Peer Reviewed Cancer Research Program, Congressionally Directed Medical Research Programs. U.S. Department of Defense , 2021 . Available: https://cdmrp.army.mil/prcrp/default [Accessed 16 Apr 2021 ].
  • Richards T ,
  • ↵ Guidance for BMJ Patient and Public Reviewers [Internet]. The BMJ . Available: https://www.bmj.com/about-bmj/resources-reviewers/guidance-patient-reviewers [Accessed 16 Apr 2021 ].
  • Rubenstein J ,

Twitter @TheLizArmy, @@crblease

Contributors Both authors contributed substantially to the manuscript. LS conceived the idea and design and drafted the text. CB refined the idea and critically revised the text.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests The authors have read and understood the BMJ policy on declaration of interests and declare the following interests: LS is a member of the BMJ Patient Advisory Panel, serves as a BMJ patient reviewer and is an ad hoc patient reviewer for the Patient-Centered Outcomes Research Institute; CB is a Keane OpenNotes scholar; both LS and CB work on OpenNotes, a philanthropically funded research initiative focused on improving transparency in healthcare.

Provenance and peer review Commissioned; externally peer reviewed.

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Peer Review Checklist

peer review research paper template

Working on a peer review? Keep this checklist handy as you go through each step.

Want a printable version of this checklist? Download the PDF

When you’re invited to review a manuscript

Confirm the manuscript is in your area of expertise

Make sure you have enough time

Check for competing interests

Related guide You’ve been invited to review. Now what?

When you’re reading the manuscript

Identify the research question and key claims

Think about context and related literature

Look at the figures and tables. Are they clear? Do they represent what the study is about?

Examine the results. Are they supported by the data?

Read the conclusions. Do they make sense?

Check the methods. Are they appropriate and reproducible?

Review the journal guidelines and publication criteria

Keep everything confidential!

Related guide How to read a manuscript as a peer reviewer

When you’re writing the report

Start with a summary of the research

State your overall impression

Number your comments and separate them into “major” and “minor” issues

Give concrete examples

Refer to specific sections and page numbers

Don’t focus on spelling and grammar

Be professional and respectful

Indicate if you’re available to look at the revised version

Include positive feedback too!

Finish on time

Related guide How to write a peer review

  • Reviewer Guidelines
  • Peer review model
  • Scope & article eligibility
  • Reviewer eligibility
  • Peer reviewer code of conduct
  • Guidelines for reviewing
  • How to submit
  • The peer-review process
  • Peer Reviewing Tips
  • Benefits for Reviewers

The genesis of this paper is the proposal that genomes containing a poor percentage of guanosine and cytosine (GC) nucleotide pairs lead to proteomes more prone to aggregation than those encoded by GC-rich genomes. As a consequence these organisms are also more dependent on the protein folding machinery. If true, this interesting hypothesis could establish a direct link between the tendency to aggregate and the genomic code.

In their paper, the authors have tested the hypothesis on the genomes of eubacteria using a genome-wide approach based on multiple machine learning models. Eubacteria are an interesting set of organisms which have an appreciably high variation in their nucleotide composition with the percentage of CG genetic material ranging from 20% to 70%. The authors classified different eubacterial proteomes in terms of their aggregation propensity and chaperone-dependence. For this purpose, new classifiers had to be developed which were based on carefully curated data. They took account for twenty-four different features among which are sequence patterns, the pseudo amino acid composition of phenylalanine, aspartic and glutamic acid, the distribution of positively charged amino acids, the FoldIndex score and the hydrophobicity. These classifiers seem to be altogether more accurate and robust than previous such parameters.

The authors found that, contrary to what expected from the working hypothesis, which would predict a decrease in protein aggregation with an increase in GC richness, the aggregation propensity of proteomes increases with the GC content and thus the stability of the proteome against aggregation increases with the decrease in GC content. The work also established a direct correlation between GC-poor proteomes and a lower dependence on GroEL. The authors conclude by proposing that a decrease in eubacterial GC content may have been selected in organisms facing proteostasis problems. A way to test the overall results would be through in vitro evolution experiments aimed at testing whether adaptation to low GC content provide folding advantage.

The main strengths of this paper is that it addresses an interesting and timely question, finds a novel solution based on a carefully selected set of rules, and provides a clear answer. As such this article represents an excellent and elegant bioinformatics genome-wide study which will almost certainly influence our thinking about protein aggregation and evolution. Some of the weaknesses are the not always easy readability of the text which establishes unclear logical links between concepts.

Another possible criticism could be that, as any in silico study, it makes strong assumptions on the sequence features that lead to aggregation and strongly relies on the quality of the classifiers used. Even though the developed classifiers seem to be more robust than previous such parameters, they remain only overall indications which can only allow statistical considerations. It could of course be argued that this is good enough to reach meaningful conclusions in this specific case.

The paper by Chevalier et al. analyzed whether late sodium current (I NaL ) can be assessed using an automated patch-clamp device. To this end, the I NaL effects of ranolazine (a well known I NaL inhibitor) and veratridine (an I NaL activator) were described. The authors tested the CytoPatch automated patch-clamp equipment and performed whole-cell recordings in HEK293 cells stably transfected with human Nav1.5. Furthermore, they also tested the electrophysiological properties of human induced pluripotent stem cell-derived cardiomyocytes (hiPS) provided by Cellular Dynamics International. The title and abstract are appropriate for the content of the text. Furthermore, the article is well constructed, the experiments were well conducted, and analysis was well performed.

I NaL is a small current component generated by a fraction of Nav1.5 channels that instead to entering in the inactivated state, rapidly reopened in a burst mode. I NaL critically determines action potential duration (APD), in such a way that both acquired (myocardial ischemia and heart failure among others) or inherited (long QT type 3) diseases that augmented the I NaL magnitude also increase the susceptibility to cardiac arrhythmias. Therefore, I NaL has been recognized as an important target for the development of drugs with either antiischemic or antiarrhythmic effects. Unfortunately, accurate measurement of I NaL is a time consuming and technical challenge because of its extra-small density. The automated patch clamp device tested by Chevalier et al. resolves this problem and allows fast and reliable I NaL measurements.

The results here presented merit some comments and arise some unresolved questions. First, in some experiments (such is the case in experiments B and D in Figure 2) current recordings obtained before the ranolazine perfusion seem to be quite unstable. Indeed, the amplitude progressively increased to a maximum value that was considered as the control value (highlighted with arrows). Can this problem be overcome? Is this a consequence of a slow intracellular dialysis? Is it a consequence of a time-dependent shift of the voltage dependence of activation/inactivation? Second, as shown in Figure 2, intensity of drug effects seems to be quite variable. In fact, experiments A, B, C, and D in Figure 2 and panel 2D, demonstrated that veratridine augmentation ranged from 0-400%. Even assuming the normal biological variability, we wonder as to whether this broad range of effect intensities can be justified by changes in the perfusion system. Has been the automated dispensing system tested? If not, we suggest testing the effects of several K + concentrations on inward rectifier currents generated by Kir2.1 channels (I Kir2.1 ).

The authors demonstrated that the recording quality was so high that the automated device allows to the differentiation between noise and current, even when measuring currents of less than 5 pA of amplitude. In order to make more precise mechanistic assumptions, the authors performed an elegant estimation of current variance (σ 2 ) and macroscopic current (I) following the procedure described more than 30 years ago by Van Driessche and Lindemann 1 . By means of this method, Chevalier et al. reducing the open channel probability, while veratridine increases the number of channels in the burst mode. We respectfully would like to stress that these considerations must be put in context from a pharmacological point of view. We do not doubt that ranolazine acts as an open channel blocker, what it seems clear however, is that its onset block kinetics has to be “ultra” slow, otherwise ranolazine would decrease peak I NaL even at low frequencies of stimulation. This comment points towards the fact that for a precise mechanistic study of ionic current modifying drugs it is mandatory to analyze drug effects with much more complicated pulse protocols. Questions thus are: does this automated equipment allow to the analysis of the frequency-, time-, and voltage-dependent effects of drugs? Can versatile and complicated pulse protocols be applied? Does it allow to a good voltage control even when generated currents are big and fast? If this is not possible, and by means of its extraordinary discrimination between current and noise, this automated patch-clamp equipment will only be helpful for rapid I NaL -modifying drug screening. Obviously it will also be perfect to test HERG blocking drug effects as demanded by the regulatory authorities.

Finally, as cardiac electrophysiologists, we would like to stress that it seems that our dream of testing drug effects on human ventricular myocytes seems to come true. Indeed, human atrial myocytes are technically, ethically and logistically difficult to get, but human ventricular are almost impossible to be obtained unless from the explanted hearts from patients at the end stage of cardiac diseases. Here the authors demonstrated that ventricular myocytes derived from hiPS generate beautiful action potentials that can be recorded with this automated equipment. The traces shown suggested that there was not alternation in the action potential duration. Is this a consistent finding? How long do last these stable recordings? The only comment is that resting membrane potential seems to be somewhat variable. Can this be resolved? Is it an unexpected veratridine effect? Standardization of maturation methods of ventricular myocytes derived from hiPS will be a big achievement for cardiac cellular electrophysiology which was obliged for years to the imprecise extrapolation of data obtained from a combination of several species none of which was representative of human electrophysiology. The big deal will be the maturation of human atrial myocytes derived from hiPS that fulfil the known characteristics of human atrial cells.

We suggest suppressing the initial sentence of section 3. We surmise that results obtained from the experiments described in this section cannot serve to understand the role of I NaL in arrhythmogenesis.

1. Van Driessche W, Lindemann B: Concentration dependence of currents through single sodium-selective pores in frog skin. Nature . 1979; 282 (5738): 519-520 PubMed Abstract | Publisher Full Text

The authors have clarified several of the questions I raised in my previous review. Unfortunately, most of the major problems have not been addressed by this revision. As I stated in my previous review, I deem it unlikely that all those issues can be solved merely by a few added paragraphs. Instead there are still some fundamental concerns with the experimental design and, most critically, with the analysis. This means the strong conclusions put forward by this manuscript are not warranted and I cannot approve the manuscript in this form.

  • The greatest concern is that when I followed the description of the methods in the previous version it was possible to decode, with almost perfect accuracy, any arbitrary stimulus labels I chose. See https://doi.org/10.6084/m9.figshare.1167456 for examples of this reanalysis. Regardless of whether we pretend that the actual stimulus appeared at a later time or was continuously alternating between signal and silence, the decoding is always close to perfect. This is an indication that the decoding has nothing to do with the actual stimulus heard by the Sender but is opportunistically exploiting some other features in the data. The control analysis the authors performed, reversing the stimulus labels, cannot address this problem because it suffers from the exact same problem. Essentially, what the classifier is presumably using is the time that has passed since the recording started.
  • The reason for this is presumably that the authors used non-independent data for training and testing. Assuming I understand correctly (see point 3), random sampling one half of data samples from an EEG trace are not independent data . Repeating the analysis five times – the control analysis the authors performed – is not an adequate way to address this concern. Randomly selecting samples from a time series containing slow changes (such as the slow wave activity that presumably dominates these recordings under these circumstances) will inevitably contain strong temporal correlations. See TemporalCorrelations.jpg in https://doi.org/10.6084/m9.figshare.1185723 for 2D density histograms and a correlation matrix demonstrating this.
  • While the revised methods section provides more detail now, it still is unclear about exactly what data were used. Conventional classification analysis report what data features (usual columns in the data matrix) and what observations (usual rows) were used. Anything could be a feature but typically this might be the different EEG channels or fMRI voxels etc. Observations are usually time points. Here I assume the authors transformed the raw samples into a different space using principal component analysis. It is not stated if the dimensionality was reduced using the eigenvalues. Either way, I assume the data samples (collected at 128 Hz) were then used as observations and the EEG channels transformed by PCA were used as features. The stimulus labels were assigned as ON or OFF for each sample. A set of 50% of samples (and labels) was then selected at random for training, and the rest was used for testing. Is this correct?
  • A powerful non-linear classifier can capitalise on such correlations to discriminate arbitrary labels. In my own analyses I used both an SVM with RBF as well as a k-nearest neighbour classifier, both of which produce excellent decoding of arbitrary stimulus labels (see point 1). Interestingly, linear classifiers or less powerful SVM kernels fare much worse – a clear indication that the classifier learns about the complex non-linear pattern of temporal correlations that can describe the stimulus label. This is further corroborated by the fact that when using stimulus labels that are chosen completely at random (i.e. with high temporal frequency) decoding does not work.
  • The authors have mostly clarified how the correlation analysis was performed. It is still left unclear, however, how the correlations for individual pairs were averaged. Was Fisher’s z-transformation used, or were the data pooled across pairs? More importantly, it is not entirely surprising that under the experimental conditions there will be some correlation between the EEG signals for different participants, especially in low frequency bands. Again, this further supports the suspicion that the classification utilizes slow frequency signals that are unrelated to the stimulus and the experimental hypothesis. In fact, a quick spot check seems to confirm this suspicion: correlating the time series separately for each channel from the Receiver in pair 1 with those from the Receiver in pair 18 reveals 131 significant (p‹0.05, Bonferroni corrected) out of 196 (14x14 channels) correlations… One could perhaps argue that this is not surprising because both these pairs had been exposed to identical stimulus protocols: one minute of initial silence and only one signal period (see point 6). However, it certainly argues strongly against the notion that the decoding is any way related to the mental connection between the particular Sender and Receiver in a given pair because it clearly works between Receivers in different pairs! However, to further control for this possibility I repeated the same analysis but now comparing the Receiver from pair 1 to the Receiver from pair 15. This pair was exposed to a different stimulus paradigm (2 minutes of initial silence and a longer paradigm with three signal periods). I only used the initial 3 minutes for the correlation analysis. Therefore, both recordings would have been exposed to only one signal period but at different times (at 1 min and 2 min for pair 1 and 15, respectively). Even though the stimulus protocol was completely different the time courses for all the channels are highly correlated and 137 out of 196 correlations are significant. Considering that I used the raw data for this analysis it should not surprise anyone that extracting power from different frequency bands in short time windows will also reveal significant correlations. Crucially, it demonstrates that correlations between Sender and Receiver are artifactual and trivial.
  • The authors argue in their response and the revision that predictive strategies were unlikely. After having performed these additional analyses I am inclined to agree. The excellent decoding almost certainly has nothing to do with expectation or imagery effects and it is irrelevant whether participants could guess the temporal design of the experiment. Rather, the results are almost entirely an artefact of the analysis. However, this does not mean that predictability is not an issue. The figure StimulusTimecourses.jpg in https://doi.org/10.6084/m9.figshare.1185723 plots the stimulus time courses for all 20 pairs as can be extracted from the newly uploaded data. This confirms what I wrote in my previous review, in fact, with the corrected data sets the problem with predictability is even greater. Out of the 20 pairs, 13 started with 1 min of initial silence. The remaining 7 had 2 minutes of initial silence. Most of the stimulus paradigms are therefore perfectly aligned and thus highly correlated. This also proves incorrect the statement that initial silence periods were 1, 2, or 3 minutes. No pair had 3 min of initial silence. It would therefore have been very easy for any given Receiver to correctly guess the protocol. It should be clear that this is far from optimal for testing such an unorthodox hypothesis. Any future experiments should employ more randomization to decrease predictability. Even if this wasn’t the underlying cause of the present results, this is simply not great experimental design.
  • The authors now acknowledge in their response that all the participants were authors. They say that this is also acknowledged in the methods section, but I did not see any statement about that in the revised manuscript. As before, I also find it highly questionable to include only authors in an experiment of this kind. It is not sufficient to claim that Receivers weren’t guessing their stimulus protocol. While I am giving the authors (and thus the participants) the benefit of the doubt that they actually believe they weren’t guessing/predicting the stimulus protocols, this does not rule out that they did. It may in fact be possible to make such predictions subconsciously (Now, if you ask me, this is an interesting scientific question someone should do an experiment on!). The fact familiar with the protocol may help that. Any future experiments should take steps to prevent this.
  • I do not follow the explanation for the binomial test the authors used. Based on the excessive Bayes Factor of 390,625 it is clear that the authors assumed a chance level of 50% on their binomial test. Because the design is not balanced, this is not correct.
  • In general, the Bayes Factor and the extremely high decoding accuracy should have given the authors reason to start. Considering the unusual hypothesis did the authors not at any point wonder if these results aren’t just far too good to be true? Decoding mental states from brain activity is typically extremely noisy and hardly affords accuracies at the level seen here. Extremely accurate decoding and Bayes Factors in the hundreds of thousands should be a tell-tale sign to check that there isn’t an analytical flaw that makes the result entirely trivial. I believe this is what happened here and thus I think this experiment serves as a very good demonstration for the pitfalls of applying such analysis without sanity checks. In order to make claims like this, the experimental design must contain control conditions that can rule out these problems. Presumably, recordings without any Sender, and maybe even when the “Receiver” is aware of this fact, should produce very similar results.

Based on all these factors, it is impossible for me to approve this manuscript. I should however state that it is laudable that the authors chose to make all the raw data of their experiment publicly available. Without this it would have impossible for me to carry out the additional analyses, and thus the most fundamental problem in the analysis would have remained unknown. I respect the authors’ patience and professionalism in dealing with what I can only assume is a rather harsh review experience. I am honoured by the request for an adversarial collaboration. I do not rule out such efforts at some point in the future. However, for all of the reasons outlined in this and my previous review, I do not think the time is right for this experiment to proceed to this stage. Fundamental analytical flaws and weaknesses in the design should be ruled out first. An adversarial collaboration only really makes sense to me for paradigms were we can be confident that mundane or trivial factors have been excluded.

This manuscript does an excellent job demonstrating significant strain differences in Burdian's paradigm. Since each Drosophila lab has their own wild type (usually Canton-S) isolate, this issue of strain differences is actually a very important one for between lab reproducibility. This work is a good reminder for all geneticists to pay attention to the population effects in the background controls, and presumably the mutant lines we are comparing.

I was very pleased to see the within-isolate behavior was consistent in replicate experiments one year apart. The authors further argue that the between-isolate differences in behavior arise from a Founder's effect, at least in the differences in locomotor behavior between the Paris lines CS_TP and CS_JC. I believe this is a very reasonable and testable hypothesis. It predicts that genetic variability for these traits exist within the populations. It should now be possible to perform selection experiments from the original CS_TP population to replicate the founding event and estimate the heritability of these traits.

Two other things that I liked about this manuscript are the ability to adjust parameters in figure 3, and our ability to download the raw data. After reading the manuscript, I was a little disappointed that the performance of the five strains in each 12 behavioral variables weren't broken down individually in a table or figure. I thought this may help us readers understand what the principle components were representing. The authors have made this data readily accessible in a downloadable spreadsheet.

This is an exceptionally good review and balanced assessment of the status of CETP inhibitors and ASCVD from a world authority in the field. The article highlights important data that might have been overlooked when promulgating the clinical value of CETPIs and related trials.

Only 2 areas need revision:

  • Page 3, para 2: the notion that these data from Papp et al . convey is critical and the message needs an explicit sentence or two at end of paragraph.
  • Page 4, Conclusion: the assertion concerning the ethics of the two Phase 3 clinical trials needs toning down. Perhaps rephrase to indicate that the value and sense of doing these trials is open to question, with attendant ethical implications, or softer wording to that effect.

The Wiley et al . manuscript describes a beautiful synthesis of contemporary genetic approaches to, with astonishing efficiency, identify lead compounds for therapeutic approaches to a serious human disease. I believe the importance of this paper stems from the applicability of the approach to the several thousand of rare human disease genes that Next-Gen sequencing will uncover in the next few years and the challenge we will have in figuring out the function of these genes and their resulting defects. This work presents a paradigm that can be broadly and usefully applied.

In detail, the authors begin with gene responsible for X-linked spinal muscular atrophy and express both the wild-type version of that human gene as well as a mutant form of that gene in S. pombe . The conceptual leap here is that progress in genetics is driven by phenotype, and this approach involving a yeast with no spine or muscles to atrophy is nevertheless and N-dimensional detector of phenotype.

The study is not without a small measure of luck in that expression of the wild-type UBA1 gene caused a slow growth phenotype which the mutant did not. Hence there was something in S. pombe that could feel the impact of this protein. Given this phenotype, the authors then went to work and using the power of the synthetic genetic array approach pioneered by Boone and colleagues made a systematic set of double mutants combining the human expressed UBA1 gene with knockout alleles of a plurality of S. pombe genes. They found well over a hundred mutations that either enhanced or suppressed the growth defect of the cells expressing UBI1. Most of these have human orthologs. My hunch is that many human genes expressed in yeast will have some comparably exploitable phenotype, and time will tell.

Building on the interaction networks of S. pombe genes already established, augmenting these networks by the protein interaction networks from yeast and from human proteome studies involving these genes, and from the structure of the emerging networks, the authors deduced that an E3 ligase modulated UBA1 and made the leap that it therefore might also impact X-linked Spinal Muscular Atrophy.

Here, the awesome power of the model organism community comes into the picture as there is a zebrafish model of spinal muscular atrophy. The principle of phenologs articulated by the Marcotte group inspire the recognition of the transitive logic of how phenotypes in one organism relate to phenotypes in another. With this zebrafish model, they were able to confirm that an inhibitor of E3 ligases and of the Nedd8-E1 activating suppressed the motor axon anomalies, as predicted by the effect of mutations in S. pombe on the phenotypes of the UBA1 overexpression.

I believe this is an important paper to teach in intro graduate courses as it illustrates beautifully how important it is to know about and embrace the many new sources of systematic genetic information and apply them broadly.

This paper by Amrhein et al. criticizes a paper by Bradley Efron that discusses Bayesian statistics ( Efron, 2013a ), focusing on a particular example that was also discussed in Efron (2013b) . The example concerns a woman who is carrying twins, both male (as determined by sonogram and we ignore the possibility that gender has been observed incorrectly). The parents-to-be ask Efron to tell them the probability that the twins are identical.

This is my first open review, so I'm not sure of the protocol. But given that there appears to be errors in both Efron (2013b) and the paper under review, I am sorry to say that my review might actually be longer than the article by Efron (2013a) , the primary focus of the critique, and the critique itself. I apologize in advance for this. To start, I will outline the problem being discussed for the sake of readers.

This problem has various parameters of interest. The primary parameter is the genetic composition of the twins in the mother’s womb. Are they identical (which I describe as the state x = 1) or fraternal twins ( x = 0)? Let y be the data, with y = 1 to indicate the twins are the same gender. Finally, we wish to obtain Pr( x = 1 | y = 1), the probability the twins are identical given they are the same gender 1 . Bayes’ rule gives us an expression for this:

Pr( x = 1 | y = 1) = Pr( x =1) Pr( y = 1 | x = 1) / {Pr( x =1) Pr( y = 1 | x = 1) + Pr( x =0) Pr( y = 1 | x = 0)}

Now we know that Pr( y = 1 | x = 1) = 1; twins must be the same gender if they are identical. Further, Pr( y = 1 | x = 0) = 1/2; if twins are not identical, the probability of them being the same gender is 1/2.

Finally, Pr( x = 1) is the prior probability that the twins are identical. The bone of contention in the Efron papers and the critique by Amrhein et al. revolves around how this prior is treated. One can think of Pr( x = 1) as the population-level proportion of twins that are identical for a mother like the one being considered.

However, if we ignore other forms of twins that are extremely rare (equivalent to ignoring coins finishing on their edges when flipping them), one incontrovertible fact is that Pr( x = 0) = 1 − Pr( x = 1); the probability that the twins are fraternal is the complement of the probability that they are identical.

The above values and expressions for Pr( y = 1 | x = 1), Pr( y = 1 | x = 0), and Pr( x = 0) leads to a simpler expression for the probability that we seek ‐ the probability that the twins are identical given they have the same gender:

Pr( x = 1 | y = 1) = 2 Pr( x =1) / [1 + Pr( x =1)] (1)

We see that the answer depends on the prior probability that the twins are identical, Pr( x =1). The paper by Amrhein et al. points out that this is a mathematical fact. For example, if identical twins were impossible (Pr( x = 1) = 0), then Pr( x = 1| y = 1) = 0. Similarly, if all twins were identical (Pr( x = 1) = 1), then Pr( x = 1| y = 1) = 1. The “true” prior lies somewhere in between. Apparently, the doctor knows that one third of twins are identical 2 . Therefore, if we assume Pr( x = 1) = 1/3, then Pr( x = 1| y = 1) = 1/2.

Now, what would happen if we didn't have the doctor's knowledge? Laplace's “Principle of Insufficient Reason” would suggest that we give equal prior probability to all possibilities, so Pr( x = 1) = 1/2 and Pr( x = 1| y = 1) = 2/3, an answer different from 1/2 that was obtained when using the doctor's prior of 1/3.

Efron(2013a) highlights this sensitivity to the prior, representing someone who defines an uninformative prior as a “violator”, with Laplace as the “prime violator”. In contrast, Amrhein et al. correctly points out that the difference in the posterior probabilities is merely a consequence of mathematical logic. No one is violating logic – they are merely expressing ignorance by specifying equal probabilities to all states of nature. Whether this is philosophically valid is debatable ( Colyvan 2008 ), but weight to that question, and it is well beyond the scope of this review. But setting Pr( x = 1) = 1/2 is not a violation; it is merely an assumption with consequences (and one that in hindsight might be incorrect 2 ).

Alternatively, if we don't know Pr( x = 1), we could describe that probability by its own probability distribution. Now the problem has two aspects that are uncertain. We don’t know the true state x , and we don’t know the prior (except in the case where we use the doctor’s knowledge that Pr( x = 1) = 1/3). Uncertainty in the state of x refers to uncertainty about this particular set of twins. In contrast, uncertainty in Pr( x = 1) reflects uncertainty in the population-level frequency of identical twins. A key point is that the state of one particular set of twins is a different parameter from the frequency of occurrence of identical twins in the population.

Without knowledge about Pr( x = 1), we might use Pr( x = 1) ~ dunif(0, 1), which is consistent with Laplace. Alternatively, Efron (2013b) notes another alternative for an uninformative prior: Pr( x = 1) ~ dbeta(0.5, 0.5), which is the Jeffreys prior for a probability.

Here I disagree with Amrhein et al. ; I think they are confusing the two uncertain parameters. Amrhein et al. state:

“We argue that this example is not only flawed, but useless in illustrating Bayesian data analysis because it does not rely on any data. Although there is one data point (a couple is due to be parents of twin boys, and the twins are fraternal), Efron does not use it to update prior knowledge. Instead, Efron combines different pieces of expert knowledge from the doctor and genetics using Bayes’ theorem.”

This claim might be correct when describing uncertainty in the population-level frequency of identical twins. The data about the twin boys is not useful by itself for this purpose – they are a biased sample (the data have come to light because their gender is the same; they are not a random sample of twins). Further, a sample of size one, especially if biased, is not a firm basis for inference about a population parameter. While the data are biased, the claim by Amrheim et al. that there are no data is incorrect.

However, the data point (the twins have the same gender) is entirely relevant to the question about the state of this particular set of twins. And it does update the prior. This updating of the prior is given by equation (1) above. The doctor’s prior probability that the twins are identical (1/3) becomes the posterior probability (1/2) when using information that the twins are the same gender. The prior is clearly updated with Pr( x = 1| y = 1) ≠ Pr( x = 1) in all but trivial cases; Amrheim et al. ’s statement that I quoted above is incorrect in this regard.

This possible confusion between uncertainty about these twins and uncertainty about the population level frequency of identical twins is further suggested by Amrhein et al. ’s statements:

“Second, for the uninformative prior, Efron mentions erroneously that he used a uniform distribution between zero and one, which is clearly different from the value of 0.5 that was used. Third, we find it at least debatable whether a prior can be called an uninformative prior if it has a fixed value of 0.5 given without any measurement of uncertainty.”

Note, if the prior for Pr( x = 1) is specified as 0.5, or dunif(0,1), or dbeta(0.5, 0.5), the posterior probability that these twins are identical is 2/3 in all cases. Efron (2013b) says the different priors lead to different results, but this result is incorrect, and the correct answer (2/3) is given in Efron (2013a) 3 . Nevertheless, a prior that specifies Pr( x = 1) = 0.5 does indicate uncertainty about whether this particular set of twins is identical (but certainty in the population level frequency of twins). And Efron’s (2013a) result is consistent with Pr( x = 1) having a uniform prior. Therefore, both claims in the quote above are incorrect.

It is probably easiest to show the (lack of) influence of the prior using MCMC sampling. Here is WinBUGS code for the case using Pr( x = 1) = 0.5.

Running this model in WinBUGS shows that the posterior mean of x is 2/3; this is the posterior probability that x = 1.

Instead of using pr_ident_twins <- 0.5, we could set this probability as being uncertain and define pr_ident_twins ~ dunif(0,1), or pr_ident_twins ~ dbeta(0.5,0.5). In either case, the posterior mean value of x remains 2/3 (contrary to Efron 2013b , but in accord with the correction in Efron 2013a ).

Note, however, that the value of the population level parameter pr_ident_twins is different in all three cases. In the first it remains unchanged at 1/2 where it was set. In the case where the prior distribution for pr_ident_twins is uniform or beta, the posterior distributions remain broad, but they differ depending on the prior (as they should – different priors lead to different posteriors 4 ). However, given the biased sample size of 1, the posterior distribution for this particular parameter is likely to be misleading as an estimate of the population-level frequency of twins.

So why doesn’t the choice of prior influence the posterior probability that these twins are identical? Well, for these three priors, the prior probability that any single set of twins is identical is 1/2 (this is essentially the mean of the prior distributions in these three cases).

If, instead, we set the prior as dbeta(1,2), which has a mean of 1/3, then the posterior probability that these twins are identical is 1/2. This is the same result as if we had set Pr( x = 1) = 1/3. In both these cases (choosing dbeta(1,2) or 1/3), the prior probability that a single set of twins is identical is 1/3, so the posterior is the same (1/2) given the data (the twins have the same gender).

Further, Amrhein et al. also seem to misunderstand the data. They note:

“Although there is one data point (a couple is due to be parents of twin boys, and the twins are fraternal)...”

This is incorrect. The parents simply know that the twins are both male. Whether they are fraternal is unknown (fraternal twins being the complement of identical twins) – that is the question the parents are asking. This error of interpretation makes the calculations in Box 1 and subsequent comments irrelevant.

Box 1 also implies Amrhein et al. are using the data to estimate the population frequency of identical twins rather than the state of this particular set of twins. This is different from the aim of Efron (2013a) and the stated question.

Efron suggests that Bayesian calculations should be checked with frequentist methods when priors are uncertain. However, this is a good example where this cannot be done easily, and Amrhein et al. are correct to point this out. In this case, we are interested in the probability that the hypothesis is true given the data (an inverse probability), not the probabilities that the observed data would be generated given particular hypotheses (frequentist probabilities). If one wants the inverse probability (the probability the twins are identical given they are the same gender), then Bayesian methods (andtherefore a prior) are required. A logical answer simply requires that the prior is constructed logically. Whether that answer is “correct” will be, in most cases, only known in hindsight.

However, one possible way to analyse this example using frequentist methods would be to assess the likelihood of obtaining the data for each of the two hypothesis (the twins are identical or fraternal). The likelihood of the twins having the same gender under the hypothesis that they are identical is 1. The likelihood of the twins having the same gender under the hypothesis that they are fraternal is 0.5. Therefore, the weight of evidence in favour of identical twins is twice that of fraternal twins. Scaling these weights so they sum to one ( Burnham and Anderson 2002 ), gives a weight of 2/3 for identical twins and 1/3 for fraternal twins. These scaled weights have the same numerical values as the posterior probabilities based on either a Laplace or Jeffreys prior. Thus, one might argue that the weight of evidence for each hypothesis when using frequentist methods is equivalent to the posterior probabilities derived from an uninformative prior. So, as a final aside in reference to Efron (2013a) , if we are being “violators” when using a uniform prior, are we also being “violators” when using frequentist methods to weigh evidence? Regardless of the answer to this rhetorical question, “checking” the results with frequentist methods doesn’t give any more insight than using uninformative priors (in this case). However, this analysis shows that the question can be analysed using frequentist methods; the single data point is not a problem for this. The claim in Armhein et al. that a frequentist analyis "is impossible because there is only one data point, and frequentist methods generally cannot handle such situations" is not supported by this example.

In summary, the comment by Amrhein et al. raises some interesting points that seem worth discussing, but it makes important errors in analysis and interpretation, and misrepresents the results of Efron (2013a) . This means the current version should not be approved.

Burnham, K.P. & D.R. Anderson. 2002. Model Selection and Multi-model Inference: a Practical Information-theoretic Approach. Springer-Verlag, New York.

Colyvan, M. 2008. Is Probability the Only Coherent Approach to Uncertainty? Risk Anal. 28: 645-652.

Efron B. (2003a) Bayes’ Theorem in the 21st Century. Science 340(6137): 1177-1178.

Efron B. (2013b) A 250-year argument: Belief, behavior, and the bootstrap. Bull Amer. Math Soc. 50: 129-146.

  • The twins are both male. However, if the twins were both female, the statistical results would be the same, so I will simply use the data that the twins are the same gender.
  • In reality, the frequency of twins that are identical is likely to vary depending on many factors but we will accept 1/3 for now.
  • Efron (2013b) reports the posterior probability for these twins being identical as “a whopping 61.4% with a flat Laplace prior” but as 2/3 in Efron (2013a) . The latter (I assume 2/3 is “even more whopping”!) is the correct answer, which I confirmed via email with Professor Efron. Therefore, Efron (2013b) incorrectly claims the posterior probability is sensitive to the choice between a Jeffreys or Laplace uninformative prior.
  • When the data are very informative relative to the different priors, the posteriors will be similar, although not identical.

I am very glad the authors wrote this essay. It is a well-written, needed, and useful summary of the current status of “data publication” from a certain perspective. The authors, however, need to be bolder and more analytical. This is an opinion piece, yet I see little opinion. A certain view is implied by the organization of the paper and the references chosen, but they could be more explicit.

The paper would be both more compelling and useful to a broad readership if the authors moved beyond providing a simple summary of the landscape and examined why there is controversy in some areas and then use the evidence they have compiled to suggest a path forward. They need to be more forthright in saying what data publication means to them, or what parts of it they do not deal with. Are they satisfied with the Lawrence et al. definition? Do they accept the critique of Parsons and Fox? What is the scope of their essay?

The authors take a rather narrow view of data publication, which I think hinders their analyses. They describe three types of (digital) data publication: Data as a supplement to an article; data as the subject of a paper; and data independent of a paper. The first two types are relatively new and they represent very little of the data actually being published or released today. The last category, which is essentially an “other” category, is rich in its complexity and encompasses the vast majority of data released. I was disappointed that the examples of this type were only the most bare-bones (Zenodo and Figshare). I think a deeper examination of this third category and its complexity would help the authors better characterize the current landscape and suggest paths forward.

Some questions the authors might consider: Are these really the only three models in consideration or does the publication model overstate a consensus around a certain type of data publication? Why are there different models and which approach is better for different situations? Do they have different business models or imply different social contracts? Might it also be worthy of typing “publishers” instead of “publications”? For example, do domain repositories vs. institutional repositories vs. publishers address the issues differently? Are these models sustaining models or just something to get us through the next 5-10 years while we really figure it out?

I think this oversimplification inhibited some deeper analysis in other areas as well. I would like to see more examination of the validation requirement beyond the lens of peer review, and I would like a deeper examination of incentives and credit beyond citation.

I thought the validation section of the paper was very relevant, but somewhat light. I like the choice of the term validation as more accurate than “quality” and it fits quite well with Callaghan’s useful distinction between technical and scientific review, but I think the authors overemphasize the peer-review style approach. The authors rightly argue that “peer-review” is where the publication metaphor leads us, but it may be a false path. They overstate some difficulties of peer-review (No-one looks at every data value? No, they use statistics, visualization, and other techniques.) while not fully considering who is responsible for what. We need a closer examination of different roles and who are appropriate validators (not necessarily conventional peers). The narrowly defined models of data publication may easily allow for a conventional peer-review process, but it is much more complex in the real-world “other” category. The authors discuss some of this in what they call “independent data validation,” but they don’t draw any conclusions.

Only the simplest of research data collections are validated only by the original creators. More often there are teams working together to develop experiments, sampling protocols, algorithms, etc. There are additional teams who assess, calibrate, and revise the data as they are collected and assembled. The authors discuss some of this in their examples like the PDS and tDAR, but I wish they were more analytical and offered an opinion on the way forward. Are there emerging practices or consensus in these team-based schemes? The level of service concept illustrated by Open Context may be one such area. Would formalizing or codifying some of these processes accomplish the same as peer-review or more? What is the role of the curator or data scientist in all of this? Given the authors’s backgrounds, I was surprised this role was not emphasized more. Finally, I think it is a mistake for science review to be the main way to assess reuse value. It has been shown time and again that data end up being used effectively (and valued) in ways that original experts never envisioned or even thought valid.

The discussion of data citation was good and captured the state of the art well, but again I would have liked to see some views on a way forward. Have we solved the basic problem and are now just dealing with edge cases? Is the “just-in-time identifier” the way to go? What are the implications? Will the more basic solutions work in the interim? More critically, are we overemphasizing the role of citation to provide academic credit? I was gratified that the authors referenced the Parsons and Fox paper which questions the whole data publication metaphor, but I was surprised that they only discussed the “data as software” alternative metaphor. That is a useful metaphor, but I think the ecosystem metaphor has broader acceptance. I mention this because the authors critique the software metaphor because “using it to alter or affect the academic reward system is a tricky prospect”. Yet there is little to suggest that data publication and corresponding citation alters that system either. Indeed there is little if any evidence that data publication and citation incentivize data sharing or stewardship. As Christine Borgman suggests, we need to look more closely at who we are trying to incentivize to do what. There is no reason to assume it follows the same model as research literature publication. It may be beyond the scope of this paper to fully examine incentive structures, but it at least needs to be acknowledged that building on the current model doesn’t seem to be working.

Finally, what is the takeaway message from this essay? It ends rather abruptly with no summary, no suggested directions or immediate challenges to overcome, no call to action, no indications of things we should stop trying, and only brief mention of alternative perspectives. What do the authors want us to take away from this paper?

Overall though, this is a timely and needed essay. It is well researched and nicely written with rich metaphor. With modifications addressing the detailed comments below and better recognizing the complexity of the current data publication landscape, this will be a worthwhile review paper. With more significant modification where the authors dig deeper into the complexities and controversies and truly grapple with their implications to suggest a way forward, this could be a very influential paper. It is possible that the definitions of “publication” and “peer-review” need not be just stretched but changed or even rejected.

  • The whole paper needs a quick copy edit. There are a few typos, missing words, and wrong verb tenses. Note the word “data” is a plural noun. E.g., Data are not software, nor are they literature. (NSICD, instead of NSIDC)
  • Page 2, para 2: “citability is addressed by assigning a PID.” This is not true, as the authors discuss on page 4, para 4. Indeed, page 4, para 4 seems to contradict itself. Citation is more than a locator/identifier.
  • In the discussion of “Data independent of any paper” it is worth noting that there may often be linkages between these data and myriad papers. Indeed a looser concept of a data paper has existed for some time, where researchers request a citation to a paper even though it is not the data nor fully describes the data (e.g the CRU temp records)
  • Page 4, para 1: I’m not sure it’s entirely true that published data cannot involve requesting permission. In past work with Indigenous knowledge holders, they were willing to publish summary data and then provide the details when satisfied the use was appropriate and not exploitive. I think those data were “published” as best they could be. A nit, perhaps, but it highlights that there are few if any hard and fast rules about data publication.
  • Page 4, para 2: You may also want to mention the WDS certification effort, which is combining with the DSA via an RDA Working Group:
  • Page 4, para 2: The joint declaration of data citation principles involved many more organizations than Force11, CODATA, and DCC. Please credit them all (maybe in a footnote). The glory of the effort was that it was truly a joint effort across many groups. There is no leader. Force11 was primarily a convener.
  • Page 4, para 6: The deep citation approach recommended by ESIP is not to just to list variables or a range of data. It is to identify a “structural index” for the data and to use this to reference subsets. In Earth science this structural index is often space and time, but many other indices are possible--location in a gene sequence, file type, variable, bandwidth, viewing angle, etc. It is not just for “straightforward” data sets.
  • Page 5, para 5: I take issue with the statement that few repositories provide scientific review. I can think of a couple dozen that do just off the top of my head, and I bet most domain repositories have some level of science review. The “scientists” may not always be in house, but the repository is a team facilitator. See my general comments.
  • Page 5, para 10: The PDS system is only unusual in that it is well documented and advertised. As mentioned, this team style approach is actually fairly common.
  • Page 6, para 3: Parsons and Fox don’t just argue that the data publication metaphor is limiting. They also say it is misleading. That should be acknowledged at least, if not actively grappled with.
  • Artifact removal: Unfortunately the authors have not updated the paper with a 2x2 table showing guns and smiles by removed data points. This could dispel criticism that an asymmetrical expectation bias that has been shown to exist in similar experiments is not driving a bias leading to inappropriate conclusions.
  • Artifact removal: Unfortunately the authors have not updated the paper with a 2x2 table showing guns and smiles by removed data points. This could dispel criticism that an asymmetrical expectation bias that has been shown to exist in similar experiments is not driving a bias leading to inappropriate conclusions. This is my strongest criticism of the paper and should be easily addressed as per my previous review comment. The fact that this simple data presentation was not performed to remove a clear potential source of spurious results is disappointing.
  • The authors have added 95% CIs to figures S1 and S2. This clarifies the scope for expectation bias in these data. The addition of error bars permits the authors’ assumption of a linear trend, indicating that the effect of sequences of either guns or smiles may not skew results. Equally, there could be either a downwards or upwards trend fitting within the confidence intervals that could be indicative of a cognitive bias that may violate the assumptions of the authors, leading to spurious results. One way to remove these doubts could be to stratify the analyses by the length of sequences of identical symbols. If the results hold up in each of the strata, this potential bias could be shown to not be present in the data. If the bias is strong, particularly in longer runs, this could indicate that the positive result was due to small numbers of longer identical runs combined with a cognitive bias rather than an ability to predict future events.

Chamberlain and Szöcs present the taxize R package, a set of functions that provides interfaces to several web tools and databases, and simplifies the process of checking, updating, correcting and manipulating taxon names for researchers working with ecological/biological data. A key feature that is repeated throughout is the need for reproducibility of science workflows and taxize provides a means to achieve this within the R software ecosystem for taxonomic search.

The manuscript is well-written and nicely presented, with a good balance of descriptive text and discourse and practical illustration of package usage. A number of examples illustrate the scope of the package, something that is fully expanded upon in the two appendices, which are a welcome addition to the paper.

As to the package, I am not overly fond of long function names; the authors should consider dropping the data source abbreviations from the function names in a future update/revision of the package. Likewise there is some inconsistency in the naming conventions used. For example there is the ’tpl_search()’ function to search The Plant List, but the equivalent function to search uBio is ’ubio_namebank()’. Whilst this may reflect specific aspects of terminology in use at the respective data stores, it does not help the user gain familiarity with the package by having them remember inconsistent function names.

One advantage of taxize is that it draws together a rich selection of data stores to query. A further suggestion for a future update would be to add generic function names, that apply to a database connection/information object. The latter would describe the resource the user wants to search and any other required information, such as the API key, etc., for example:

The user function to search would then be ’search(foo, "Abies")’. Similar generically named functions would provide the primary user-interface, thus promoting a more consistent toolbox at the R level. This will become increasingly relevant as the scope of taxize increases through the addition of new data stores that the package can access.

In terms of presentation in the paper, I really don’t like the way the R code inputs merge with the R outputs. I know the author of Knitr doesn’t like the demarcation of output being polluted by the R prompt, but I do find it difficult parsing the inputs/outputs you show because often there is no space between them and users not familiar with R will have greater difficulties than I. Consider adding in more conventional indications of R outputs, or physically separate input from output by breaking up the chunks of code to have whitespace between the grey-background chunks. Related, in one location I noticed something amiss with the layout; in the first code block at the top of page 5, the printed output looks wrong here. I would expect the attributes to print on their own line and the data in the attribute to also be on its own separate line.

Note also, the inconsistency in the naming of the output object columns. For example, in the two code chunks shown in column 1 of page 4, the first block has an object printed with column names ’matched_name’ and ’data_source_title’, whilst camelCase is used in the outputs shown in the second block. As the package is revised and developed, consider this and other aspects of providing a consistent presentation to the user.

I was a little confused about the example in the section Resolve Taxonomic Names on page 4. Should the taxon name be “Helianthus annuus” or “Helianthus annus” ? In the ‘mynames’ definition you include ‘Helianthus annuus’ in the character vector but the output shown suggests that the submitted name was ‘Helianthus annus’ (1 “u”) in rows with rownames 9 and 10 in the output shown.

Other than that there were the following minor observations:

  • Abstract: replace “easy” with “simple” in “...fashion that’s easy...” , and move the details about availability and the URI to the end of the sentence.
  • Page 2, Column 1, Paragraph 2: You have “In addition, there is no one authoritative taxonomic names source...” , which is a little clumsy to read. How about “In addition, there is no one authoritative source of taxonomic names... ” ?
  • Pg 2, C1, P2-3: The abbreviated data sources are presented first (in paragraph 2) and subsequently defined (in para 3). Restructure this so that the abbreviated forms are explained upon first usage.
  • Pg 2, C2, P2: Most R packages are “in development” so I would drop the qualifier and reword the opening sentence of the paragraph.
  • Pg 2, C2, P6: Change “and more can easily be added” to “and more can be easily added” seems to flow better?
  • Pg 5, paragraph above Figure 1: You refer to converting the object to an **ape** *phylo* object and then repeat essentially the same information in the next sentence. Remove the repetition.
  • Pg 6, C1: The header may be better as “Which taxa are children of the taxon of interest” .
  • Pg 6: In the section “IUCN status”, the term “we” is used to refer to both the authors and the user. This is confusing. Reserve “we” for reference to the authors and use something else (“a user” perhaps) for the other instances. Check this throughout the entire manuscript.
  • Pg 6, C2: in the paragraph immediately below the ‘grep()’ for “RAG1”, two consecutive sentences begin with “However”.
  • Pg 7: The first sentence of “Aggregating data....” reads “In biology, one can asks questions...” . It should be “one asks” or “one can ask” .
  • Pg 7, Conclusions: The first sentence reads “information is increasingly sought out by biologists” . I would drop “out” as “sought” is sufficient on its own.
  • Appendices: Should the two figures in the Appendices have a different reference to differentiate them from Figure 1 in the main body of the paper? As it stands, the paper has two Figure 1s, one on page 5 and a second on page 12 in the Appendix.
  • On Appendix Figure 2: The individual points are a little large. Consider reducing the plotting character size. I appreciate the effect you were going for with the transparency indicating density of observation through overplotting, but the effect is weakened by the size of the individual points.
  • Should the phylogenetic trees have some scale to them? I presume the height of the stems is an indication of phylogenetic distance but the figure is hard to calibrate without an associated scale. A quick look at Paradis (2012) Analysis of Phylogenetics and Evolution with R would suggest however that a scale is not consistently applied to these trees. I am happy to be guided by the authors as they will be more familiar with the conventions than I.

Hydbring and Badalian-Very summarize in this review, the current status in the potential development of clinical applications based on miRNAs’ biology. The article gives an interesting historical and scientific perspective on a field that has only recently boomed.

Hydbring and Badalian-Very summarize in this review, the current status in the potential development of clinical applications based on miRNAs’ biology. The article gives an interesting historical and scientific perspective on a field that has only recently boomed; focusing mostly on the two main products in the pipeline of several biotech companies (in Europe and USA) which work with miRNAs-based agents, disease diagnostics and therapeutics. Interestingly, not only the specific agents that are being produced are mentioned, but also clever insights in the important cellular pathways regulated by key miRNAs are briefly discussed.

Minor points to consider in subsequent versions:

  • Page 2; paragraph ‘Genomic location and transcription of microRNAs’ : the concept of miRNA clusters and precursors could be a bit better explained.
  • Page 2; paragraph ‘Genomic location and transcription of microRNAs’ : when discussing the paper by the laboratory of Richard Young (reference 16); I think it is important to mention that that particular study refers to stem cells.
  • Page 2; paragraph ‘Processing of microRNAs’ : “Argonate” should be replaced by “Argonaute”.
  • Page 3; paragraph ‘MicroRNAs in disease diagnostics’ : are miR-15a and 16-1 two different miRNAs? I suggest mentioning them as: miR-15a and miR-16-1 and not using a slash sign (/) between them.
  • Page 4; paragraph ‘Circulating microRNAs’ : I am a bit bothered by the description of multiple sclerosis (MS) only as an autoimmune disease. Without being an expert in the field, I believe that there are other hypotheses related to the etiology of MS.
  • Page 5; paragraph ‘Clinical microRNA diagnostics’ : Does ‘hsa’ in hsa-miR-205 mean something?
  • Page 5; paragraph ‘Clinical microRNA diagnostics’ : the authors mention the company Asuragen, Austin, TX, USA but they do not really say anything about their products. I suggest to either remove the reference to that company or to include their current pipeline efforts.
  • Page 6; paragraph ‘MicroRNAs in therapeutics’ : in the first paragraph the authors suggest that miRNAs-based therapeutics should be able to be applied with “minimal side-effects”. Since one miRNA can affect a whole gene program, I found this a bit counterintuitive; I was wondering if any data has been published to support that statement. Also, in the same paragraph, the authors compare miRNAs to protein inhibitors, which are described as more specific and/or selective. I think there are now good indications to think that protein inhibitors are not always that specific and/or selective and that such a property actually could be important for their evidenced therapeutic effects.
  • Page 6; paragraph ‘MicroRNAs in therapeutics’ : I think the concept of “antagomir” is an important one and could be better highlighted in the text.
  • Throughout the text (pages 3, 5, 6, and 7): I am a bit bothered by separating the word “miRNA” or “miRNAs” at the end of a sentence in the following way: “miR-NA” or “miR-NAs”. It is a bit confusing considering the particular nomenclature used for miRNAs. That was probably done during the formatting and editing step of the paper.
  • I was wondering if the authors could develop a bit more the general concept that seems to indicate that in disease (and in particular in cancer) the expression and levels of miRNAs are in general downregulated. Maybe some papers have been published about this phenomenon?

The authors describe their attempt to reproduce a study in which it was claimed that mild acid treatment was sufficient to reprogramme postnatal splenocytes from a mouse expressing GFP in the oct4 locus to pluripotent stem cells. The authors followed a protocol that has recently become available as a technical update of the original publication.

They report obtaining no pluripotent stem cells expressing GFP driven over the same time period of several days described in the original publication. They describe observation of some green fluorescence that they attributed to autofluorescence rather than GFP since it coincided with PI positive dead cells. They confirmed the absence of oct4 expression by RT-PCR and also found no evidence for Nanog or Sox2, also markers of pluripotent stem cells.

The paper appears to be an authentic attempt to reproduce the original study, although the study might have had additional value with more controls: “failure to reproduce” studies need to be particularly well controlled.

Examples that could have been valuable to include are:

  • For the claim of autofluorescence: the emission spectrum of the samples would likely have shown a broad spectrum not coincident with that of GFP.
  • The reprogramming efficiency of postnatal mouse splenocytes using more conventional methods in the hands of the authors would have been useful as a comparison. Idem the lung fibroblasts.
  • There are no positive control samples (conventional mESC or miPSC) in the qPCR experiments for pluripotency markers. This would have indicated the biological sensitivity of the assay.
  • Although perhaps a sensitive issue, it might have been helpful if the authors had been able to obtain samples of cells (or their mRNA) from the original authors for simultaneous analysis.

In summary, this is a useful study as it is citable and confirms previous blog reports, but it could have been improved by more controls.

The article is well written, treats an actual problem (the risk of development of valvulopathy after long-term cabergoline treatment in patients with macroprolactinoma) and provides evidence about the reversibility of valvular changes after timely discontinuation of DA treatment.

Title and abstract: The title is appropriate for the content of the article. The abstract is concise and accurately summarizes the essential information of the paper although it would be better if the authors define more precisely the anatomic specificity of valvulopathy – mild mitral regurgitation.

Case report: The clinical case presentation is comprehensive and detailed but there are some minor points that should be clarified:

  • Please clarify the prolactin levels at diagnosis. In the Presentation section (line 3) “At presentation, prolactin level was found to be greater than 1000 ng/ml on diluted testing” but in the section describing the laboratory evaluation at diagnosis (line 7) “Prolactin level was 55 ng/ml”. Was the difference due to so called “hook effect”?
  • Figure 1: In the text the follow-up MR imaging is indicated to be “after 10 months of cabergoline treatment” . However, the figures 1C and 1D represent 2 years post-treatment MR images. Please clarify.
  • Figure 2: Echocardiograms 2A and 2B are defined as baseline but actually they correspond to the follow-up echocardiographic assessment at the 4th year of cabergoline treatment. Did the patient undergo a baseline (prior to dopamine agonist treatment) echocardiographic evaluation? If he did not, it should be mentioned as study limitation in the Discussion section.
  • The mitral valve thickness was mentioned to be normal. Did the echographic examination visualize increased echogenicity (hyperechogenicity) of the mitral cusps?
  • How could you explain the decrease of LV ejection fraction (from 60-65% to 50-55%) after switching from cabergoline to bromocriptine treatment and respectively its increase to 62% after doubling the bromocriptine daily dose? Was LV function estimated always by the same method during the follow-up?
  • Final paragraph: Authors conclude that early discontinuation and management with bromocriptine may be effective in reversing cardiac valvular dysfunction. Even though, regular echocardiographic follow up should be considered in patients who are expected to be on long-term high dose treatment with bromocriptine regarding its partial 5-HT2b agonist activity.

This is an interesting topic: as the authors note, the way that communicators imagine their audiences will shape their output in significant ways. And I enjoyed what clearly has the potential to be a very rich data set.

This is an interesting topic: as the authors note, the way that communicators imagine their audiences will shape their output in significant ways. And I enjoyed what clearly has the potential to be a very rich data set. But I have some reservations about the adequacy of that data set, as it currently stands, given the claims the authors make; the relevance of the analytical framework(s) they draw upon; and the extent to which their analysis has offered significant new insights ‐ by which I mean, I would be keen to see the authors push their discussion further. My suggestions are essentially that they extend the data set they are working with to ensure that their analysis is both rigorous and generalisable, an re-consider the analytical frame they use. I will make some more concrete comments below.

With regard to the data: my feeling is that 14 interviews is a rather slim data set, and that this is heightened by the fact that they were all carried out in a single location, and recruited via snowball sampling and personal contacts. What efforts have the authors made to ensure that they are not speaking to a single, small, sub-community in the much wider category of science communicators? ‐ a case study, if you like, of a particular group of science communicators in North Carolina? In addition, though the authors reference grounded theory as a method for analysis, I got little sense of the data reaching saturation. The reliance on one-off quotes, and on the stories and interests of particular individuals, left me unsure as to how representative interview extracts were. I would therefore recommend either that the data set is extended by carrying out more interviews, in a wider variety of locations (e.g. other sites in the US), or that it is redeveloped as a case study of a particular local professional community. (Which would open up some fascinating questions ‐ how many of these people know each other? What spaces, online or offline, do they interact in, and do they share knowledge, for instance about their audiences? Are there certain touchstone events or publics they communally make reference to?)

As a more minor point with regard to the data set and what the authors want it to do, there were some inconsistencies as to how the study was framed. On p.2 they variously describe the purpose as to “understand the experiences and perspectives of science communicators” and the goals as identifying “the basic interests and value orientations attributed to lay audiences by science communicators”. Later, on p.5, they note that the “research is inductive and seeks to build theory rather than generalizable claims”, while in the Discussion they talk again about having identified communicators‘ “personal motivations” (p.12). There are a number of questions left hanging: is the purpose to understand communicator experiences ‐ in which case why focus on perceptions of audiences? Where is theory being built, and in what ways can this be mobilised in future work? The way that the study is framed and argued as a whole needs, I would suggest, to be clarified.

Relatedly, my sense is that some of this confusion is derived from what I find a rather busy analytical framework. I was not convinced of the value of combining inductive and deductive coding: if the ‘human value typology’ the authors use is ‘universal’, then what is added by open coding? Or, alternatively, why let their open coding, and their findings from this, be constrained by an additional, rather rigid, framework? The addition of the considerable literature on news values to the mix makes the discussion more confusing again. I would suggest that the authors either make much more clear the value of combining these different approaches ‐ building new theory outlining how they relate, and can be jointly mobilised in practice ‐ or fix on one. (My preference would be to focus on the findings from the open coding ‐ but that reflects my own disciplinary biases.)

A more minor analytical point: the authors note that their interviewees come from slightly different professions, and communicate through different formats, have different levels of experience, and different educational backgrounds ‐ but as far as I can see there is no comparative analysis based on this. Were there noticeable differences in the interview talk based on these categorisations? Or was the data set too small to identify any potential contrasts or themes? A note explaining this would be useful.

My final point has reference to the potential that this data set has, particularly if it is extended and developed. I would like to encourage the authors to take their analysis further: at the moment, I was not particularly surprised by the ways in which the communicators referenced news values or imagined their audiences. But it seems to me that the analytical work is not yet complete. What does it mean that communicators imagine audience values and preferences in the way that they do ‐ who is included and excluded by these imaginations? One experiment might be to consider what ‘ideal type’ publics are created in the communicators’ talk. What are the characteristics of the audiences constructed in the interviews and ‐ presumably ‐ in the communicative products of interviewees? What would these people look like? There are also some tantalizing hints in the Discussion that are not really discussed in the Findings ‐ of, for instance, the way in which communicator’s personal motivations may combine with their perceptions of audiences to shape their products. How does this happen? These are, of course, suggestions. But my wider point is that the authors need to show more clearly what is original and useful in their findings ‐ what it is, exactly, that will be important to other scholars in the field.

I hope my comments make sense ‐ please do not hesitate to contact me if not.

This is an interesting article and piece of software. I think it contributes towards further alternatives to easily visualize high dimensionality data on the web. It’s simple and easy to embed into other web frameworks or applications.

a) About the software

  • CSV format . It was hard to guess the expected format. The authors need to add a syntax description of the CSV format at the help page.
  • Simple HTML example . It will be easy to test HeatmapViewer (HmV) if you add a simple downloadable example file with the minimum required HTML-JavaScript to set up a HmV (without all the CSV import code).
  • Color scale . HmV only implements a simple three point linear color scale. For me this is the major weakness of HmV. It will be very convenient that in the next HmV release the user can give as a parameter a function that manages the score to color conversion.

b) About the paper

  • http://www.broadinstitute.org/gsea (desktop)
  • http://jheatmap.github.io/jheatmap/ (website)
  • http://www.gitools.org/ (desktop)
  • http://blog.nextgenetics.net/demo/entry0044/ (website)
  • http://docs.scipy.org/doc/numpy/reference/generated/numpy.histogram2d.html (python)
  • http://matplotlib.org/api/pyplot_api.html (python)
  • Predicted protein mutability landscape: The authors say: “Without using a tool such as the HeatmapViewer, we could hardly obtain an overview of the protein mutability landscape”. This paragraph seems to suggest that you can explore the data with HmV. I think that HmV is a good tool to report your data, but not to explore it.
  • Conclusions: The authors say: “... provides a new, powerful way to generate and display matrix data in web presentations and in publications.” To use heat maps in web presentations and publications is nothing new. I think that HmV makes it easier and user-friendly, but it’s not new.

This article addresses the links between habitat condition and an endangered bird species in an important forest reserve (ASF) in eastern Kenya. It addresses an important topic, especially given ongoing anthropogenic pressures on this and similar types of forest reserves in eastern Kenya and throughout the tropics. Despite the rather small temporal and spatial extent of the study, it should make an important contribution to bird and forest conservation.

This article addresses the links between habitat condition and an endangered bird species in an important forest reserve (ASF) in eastern Kenya. It addresses an important topic, especially given ongoing anthropogenic pressures on this and similar types of forest reserves in eastern Kenya and throughout the tropics. Despite the rather small temporal and spatial extent of the study, it should make an important contribution to bird and forest conservation. There are a number of issues with the methods and analysis that need to be clarified/addressed however; furthermore, some of the conclusions overreach the data collected, while other important results are given less emphasis that they warrant. Below are more specific comments by section:

The conclusion that human-driven tree removal is an important contributor to the degradation of ASF is reasonable given the data reported in the article. Elephant damage, while clearly likely a very big contributor to habitat modification in ASF, was not the focus of the study (the authors state clearly in the Discussion that elephant damage was not systematically quantified, and thus no data were analyzed) ‐ and thus should only be mentioned in passing here ‐ if at all.

More information about the life history ecology of A. Sokokensis would provide welcome context here. A bit more detail about breeding sites as well as dispersal behavior etc. would be helpful – and especially why these and other aspects render the Pipit a good indicator species/proxy for habitat condition. This could be revisited in the Discussion as links are made between habitat conditions and occurrence of the bird (where you discuss the underlying mechanisms for why it thrives in some parts of ASF and not others, and why it’s abundance correlate strongly with some types of disturbance and not others). Again, you reference other studies that have explored other species in ASF and forest disturbance, but do not really explicitly state why the Pipit is a particularly important indicator of forest condition.

  • Bird Survey: As described, all sightings and calls were recorded and incorporated into distance analysis – but it is not clear here whether or not distances to both auditory and visual encounters were measured the same way (i.e., with the rangefinder). Please clarify.
  • Floor litter sampling: Not clear here whether or not litter cover was recorded as a continuous or categorical variable (percentage). If not, please describe percentage “categories” used.
  • Mean litter depth graph (Figure 2) and accompanying text reports the means and sd but no post-hoc comparison test (e.g. Tukey HSD) – need to report the stats on which differences were/were not significant.
  • Figure 3 – you indicate litter depth was better predictor of bird abundance than litter cover, but r-squared is higher for litter cover. Need to clarify (and also indicate why you chose only to shown depth values in Figure 3.
  • The linear equation can be put in Figure 3 caption (not necessary to include in text).
  • Figure 4 – stats aren’t presented here; also, the caption states that tree loss and leaf litter are inversely correlated – this might be taken to mean, given discussion (below) about pruning, that there could be a poaching threshold below which poaching may pay dividends to Pipits (and above which Pipits are negatively affected). This warrants further exploration/elaboration.
  • The pruning result is arguably the most important one here – this suggests an intriguing trade-off between poaching and bird conservation (in particular, the suggestion that pruning by poachers may bolster Pipit populations – or at the very least mitigate against other aspects of habitat degradation). Worth highlighting this more in Discussion.
  • Last sentence on p. 7 suggests causality (“That is because…”) – but your data only support correlation (one can imagine that there may have been other extrinsic or intrinsic drivers of population decline).
  • P. 8: discussion of classification of habitat types in ASF is certainly interesting, but could be made much more succinct in keeping with focus of this paper.
  • P. 9, top: first paragraph could be expanded – as noted before, tradeoff between poaching/pruning and Pipit abundance is worth exploring in more depth. Could your results be taken as a prescription for understory pruning as a conservation tool for the Sokoke Pipit or other threatened species? More detail here would be welcome (and also in Conclusion); in subsequent paragraph about Pipit foraging behavior and specific relationship to understory vegetation at varying heights could be incorporated into this discussion. Is there any info about optimal perch height for foraging or for flying through the understory? Linking to results of other studies in ASF, is there potential for positive correlations with optimal habitat conditions for the other important bird species in ASF in order to make more general conclusions about management?

Bierbach and co-authors investigated the topic of the evolution of the audience effect in live bearing fishes, by applying a comparative method. They specifically focused on the hypothesis that sperm competition risk, arising from male mate choice copying, and avoidance of aggressive interactions play a key role in driving the evolution of audience-induced changes in male mate choice behavior.

Bierbach and co-authors investigated the topic of the evolution of the audience effect in live bearing fishes, by applying a comparative method. They specifically focused on the hypothesis that sperm competition risk, arising from male mate choice copying, and avoidance of aggressive interactions play a key role in driving the evolution of audience-induced changes in male mate choice behavior. The authors found support to their hypothesis of an influence of SCR on the evolution of deceptive behavior as their findings at species level showed a positive correlation between mean sexual activity and the occurrence of deceptive behavior. Moreover, they found a positive correlation between mean aggressiveness and sexual activity but they did not detect a relationship between aggressiveness and audience effects.

The manuscript is certainly well written and attractive, but I have some major concerns on the data analyses that prevent me to endorse its acceptance at the present stage.

I see three main problems with the statistics that could have led to potentially wrong results and, thus, to completely misleading conclusions.

  • First of all the Authors cannot run an ANCOVA in which there is a significant interaction between factor and covariate Tab. 2 (a). Indeed, when the assumption of common slopes is violated (as in their case), all other significant terms are meaningless. They might want to consider alternative statistical procedures, e.g. Johnson—Neyman method.
  • Second, the Authors cannot retain into the model a non significant interaction term, as this may affect estimations for the factors Tab. 2 (d). They need to remove the species x treatment interaction (as they did for other non significant terms, see top left of the same page 7).
  • The third problem I see regards all the GLMs in which species are compared. Authors entered the 'species' level as fixed factor when species are clearly a random factor. Entering species as fixed factors has the effect of badly inflating the denominator degrees of freedom, making authors’ conclusions far too permissive. They should, instead, use mixed LMs, in which species are the random factor. They should also take care that the degrees of freedom are approximately equal to the number of species (not the number of trials). To do so, they can enter as random factor the interaction between treatment and species.

Data need to be re-analyzed relying on the proper statistical procedures to confirm results and conclusions.

A more theoretical objection to the authors’ interpretation of results (supposing that results will be confirmed by the new analyses) could emerge from the idea that male success in mating with the preferred female may reduce the probability of immediate female’s re-mating, and thus reduce the risk of sperm competition on the short term. As a consequence, it may be not beneficial to significantly increase the risk of losing a high quality and inseminated female for a cost that will not be paid with certainty. The authors might want to consider also this for discussion.

Lastly, I think that the scenario generated from comparative studies at species level may be explained by phylogenetic factors other than sexual selection. Only the inclusion of phylogeny, that allow to account for the shared history among species, into data analyses can lead to unequivocal adaptive explanations for the observed patterns. I see the difficulty in doing this with few species, as it is the case of the present study, but I would suggest the Authors to consider also this future perspective. Moreover, a phylogenetic comparative study would be aided by the recent development of a well-resolved phylogenetic tree for the genus Poecilia (Meredith 2011).

Page 3: the authors should specify that also part of data on male aggressiveness (3 species from Table 1) come from previous studies, as they do for data on deceptive male mating behavior.

Page 5: since data on mate choice come from other studies is it so necessary to report a detailed description of methods for this section? Maybe the authors could refer to the already published methods and only give a brief additional description.

Page 6: how do the authors explain the complete absence of aggressive displays between the focal male and the audience male during the mate choice experiments? This sounds curious if considering that in all the examined species aggressive behaviors and dominance establishment are always observed during dyadic encounters.

In their response to my previous comments, the authors have clarified that only the data from the “Experimental phase” were used to calculate prediction accuracy. However, if I now understand the analysis procedure correctly, there are serious concerns with the approach adopted.

First, let me state what I now understand the analysis procedure to be:

  • For each subject the PD values across the 20 trials were converted to z-scores.
  • For each stimulus, the mean z-score was calculated.
  • The sign of the mean z-score for each stimulus was used to make predictions.
  • For each of the 20 trials, if the sign of the z-score on that trial was the same as for the mean z-score for that stimulus, a hit (correct prediction) was assigned. In contrast, if the sign of the z-score on that trial was the opposite as for the mean z-score for that stimulus, a miss (incorrect prediction) was assigned.
  • For each stimulus the total hits and misses were calculated.
  • Average hits (correct prediction) for each stimulus was calculated across subjects.

If this is a correct description of the procedure, the problem is that the same data were used to determine the sign of the z-score that would be associated with a correct prediction and to determine the actual correct predictions. This will effectively guarantee a correct prediction rate above chance.

To check if this is true, I quickly generated random data and used the analysis procedure as laid out above (see MATLAB code below). Across 10,000 iterations of 100 random subjects, the average “prediction” accuracy was ~57% for each stimulus (standard deviation, 1.1%), remarkably similar to the values reported by the authors in their two studies. In this simulation, I assumed that all subjects contributed 20 trials, but in the actual data analyzed in the study, some subjects contributed fewer than 20 trials due to artifacts in the pupil measurements.

If the above description of the analysis procedure is correct, then I think the authors have provided no evidence to support pupil dilation prediction of random events, with the results reflecting circularity in the analysis procedure.

However, if the above description of the procedure is incorrect, the authors need to clarify exactly what the analysis procedure was, perhaps by providing their analysis scripts.

I think this paper excellent and is an important addition to the literature. I really like the conceptualization of a self-replicating cycle as it illustrates the concept that the “problem” starts with the neuron, i.e., due to one or more of a variety of insults, the neuron is negatively impacted and releases H1, which in turn activates microglia with over expression of cytokines that may, when limited, foster repair but when activated becomes chronic (as is demonstrated here with the potential of cyclic H1 release) and thus facilitates neurotoxicity. I hope the authors intend to measure cytokine expression soon, especially IL-1 and TNF in both astrocytes and microglia, and S100B in astrocytes.

In more detail, Gilthorpe and colleagues provide novel experimental data that demonstrate a new role for a specific histone protein—the linker histone, H1—in neurodegeneration. This study, which was originally designed to identify axonal chemorepellents, actually provided a previously unknown role for H1, as well as other novel and thought provoking results. Fortuitously, as sometimes happens, the authors had a pleasant surprise: their results set some old dogmas on their respective ears and opened up new avenues of approach for studying the role of histones in self-amplification of neurodegenerative cycles. In point, they show that H1 is not just a nice little partner of nuclear DNA as previously thought. H1 is released from ‘damaged’ (or leaky) neurons, kills adjacent healthy neurons, and promotes a proinflammatory profile in both microglia and astrocytes.

Interestingly, the authors’ conceptualization of a damaged neuron → H1 release → healthy neuron killing cycle does not take into account the H1-mediated proinflammatory glial response. This facet of the study opens for these investigators a new avenue they may wish to follow: the role of H1 in stimulation of neuroinflammation with overexpression of cytokines. This is interesting, as neuronal injury has been shown to set in motion an acute phase response that activates glia, increases their expression of cytokines (interleukin-1 and S100B), which, in turn, induce neurons to produce excess Alzheimer-related proteins such as βAPP and ApoE (favoring formation of mature Aβ/ApoE plaques), activated MAPK-p38 and hyperphosphorylated tau (favoring formation of neurofibrillary tangles), and α synuclein (favoring formation of Lewy bodies). To date, the neuronal response shown responsible for stimulating glia is neuronal stress related release of sAPP, but these H1 results from Gilthorpe and colleagues may contribute to or exacerbate the role of sAPP.

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How to Write and Publish a Research Paper for a Peer-Reviewed Journal

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  • Published: 30 April 2020
  • Volume 36 , pages 909–913, ( 2021 )

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  • Clara Busse   ORCID: orcid.org/0000-0002-0178-1000 1 &
  • Ella August   ORCID: orcid.org/0000-0001-5151-1036 1 , 2  

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Communicating research findings is an essential step in the research process. Often, peer-reviewed journals are the forum for such communication, yet many researchers are never taught how to write a publishable scientific paper. In this article, we explain the basic structure of a scientific paper and describe the information that should be included in each section. We also identify common pitfalls for each section and recommend strategies to avoid them. Further, we give advice about target journal selection and authorship. In the online resource 1 , we provide an example of a high-quality scientific paper, with annotations identifying the elements we describe in this article.

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Avoid common mistakes on your manuscript.

Introduction

Writing a scientific paper is an important component of the research process, yet researchers often receive little formal training in scientific writing. This is especially true in low-resource settings. In this article, we explain why choosing a target journal is important, give advice about authorship, provide a basic structure for writing each section of a scientific paper, and describe common pitfalls and recommendations for each section. In the online resource 1 , we also include an annotated journal article that identifies the key elements and writing approaches that we detail here. Before you begin your research, make sure you have ethical clearance from all relevant ethical review boards.

Select a Target Journal Early in the Writing Process

We recommend that you select a “target journal” early in the writing process; a “target journal” is the journal to which you plan to submit your paper. Each journal has a set of core readers and you should tailor your writing to this readership. For example, if you plan to submit a manuscript about vaping during pregnancy to a pregnancy-focused journal, you will need to explain what vaping is because readers of this journal may not have a background in this topic. However, if you were to submit that same article to a tobacco journal, you would not need to provide as much background information about vaping.

Information about a journal’s core readership can be found on its website, usually in a section called “About this journal” or something similar. For example, the Journal of Cancer Education presents such information on the “Aims and Scope” page of its website, which can be found here: https://www.springer.com/journal/13187/aims-and-scope .

Peer reviewer guidelines from your target journal are an additional resource that can help you tailor your writing to the journal and provide additional advice about crafting an effective article [ 1 ]. These are not always available, but it is worth a quick web search to find out.

Identify Author Roles Early in the Process

Early in the writing process, identify authors, determine the order of authors, and discuss the responsibilities of each author. Standard author responsibilities have been identified by The International Committee of Medical Journal Editors (ICMJE) [ 2 ]. To set clear expectations about each team member’s responsibilities and prevent errors in communication, we also suggest outlining more detailed roles, such as who will draft each section of the manuscript, write the abstract, submit the paper electronically, serve as corresponding author, and write the cover letter. It is best to formalize this agreement in writing after discussing it, circulating the document to the author team for approval. We suggest creating a title page on which all authors are listed in the agreed-upon order. It may be necessary to adjust authorship roles and order during the development of the paper. If a new author order is agreed upon, be sure to update the title page in the manuscript draft.

In the case where multiple papers will result from a single study, authors should discuss who will author each paper. Additionally, authors should agree on a deadline for each paper and the lead author should take responsibility for producing an initial draft by this deadline.

Structure of the Introduction Section

The introduction section should be approximately three to five paragraphs in length. Look at examples from your target journal to decide the appropriate length. This section should include the elements shown in Fig.  1 . Begin with a general context, narrowing to the specific focus of the paper. Include five main elements: why your research is important, what is already known about the topic, the “gap” or what is not yet known about the topic, why it is important to learn the new information that your research adds, and the specific research aim(s) that your paper addresses. Your research aim should address the gap you identified. Be sure to add enough background information to enable readers to understand your study. Table 1 provides common introduction section pitfalls and recommendations for addressing them.

figure 1

The main elements of the introduction section of an original research article. Often, the elements overlap

Methods Section

The purpose of the methods section is twofold: to explain how the study was done in enough detail to enable its replication and to provide enough contextual detail to enable readers to understand and interpret the results. In general, the essential elements of a methods section are the following: a description of the setting and participants, the study design and timing, the recruitment and sampling, the data collection process, the dataset, the dependent and independent variables, the covariates, the analytic approach for each research objective, and the ethical approval. The hallmark of an exemplary methods section is the justification of why each method was used. Table 2 provides common methods section pitfalls and recommendations for addressing them.

Results Section

The focus of the results section should be associations, or lack thereof, rather than statistical tests. Two considerations should guide your writing here. First, the results should present answers to each part of the research aim. Second, return to the methods section to ensure that the analysis and variables for each result have been explained.

Begin the results section by describing the number of participants in the final sample and details such as the number who were approached to participate, the proportion who were eligible and who enrolled, and the number of participants who dropped out. The next part of the results should describe the participant characteristics. After that, you may organize your results by the aim or by putting the most exciting results first. Do not forget to report your non-significant associations. These are still findings.

Tables and figures capture the reader’s attention and efficiently communicate your main findings [ 3 ]. Each table and figure should have a clear message and should complement, rather than repeat, the text. Tables and figures should communicate all salient details necessary for a reader to understand the findings without consulting the text. Include information on comparisons and tests, as well as information about the sample and timing of the study in the title, legend, or in a footnote. Note that figures are often more visually interesting than tables, so if it is feasible to make a figure, make a figure. To avoid confusing the reader, either avoid abbreviations in tables and figures, or define them in a footnote. Note that there should not be citations in the results section and you should not interpret results here. Table 3 provides common results section pitfalls and recommendations for addressing them.

Discussion Section

Opposite the introduction section, the discussion should take the form of a right-side-up triangle beginning with interpretation of your results and moving to general implications (Fig.  2 ). This section typically begins with a restatement of the main findings, which can usually be accomplished with a few carefully-crafted sentences.

figure 2

Major elements of the discussion section of an original research article. Often, the elements overlap

Next, interpret the meaning or explain the significance of your results, lifting the reader’s gaze from the study’s specific findings to more general applications. Then, compare these study findings with other research. Are these findings in agreement or disagreement with those from other studies? Does this study impart additional nuance to well-accepted theories? Situate your findings within the broader context of scientific literature, then explain the pathways or mechanisms that might give rise to, or explain, the results.

Journals vary in their approach to strengths and limitations sections: some are embedded paragraphs within the discussion section, while some mandate separate section headings. Keep in mind that every study has strengths and limitations. Candidly reporting yours helps readers to correctly interpret your research findings.

The next element of the discussion is a summary of the potential impacts and applications of the research. Should these results be used to optimally design an intervention? Does the work have implications for clinical protocols or public policy? These considerations will help the reader to further grasp the possible impacts of the presented work.

Finally, the discussion should conclude with specific suggestions for future work. Here, you have an opportunity to illuminate specific gaps in the literature that compel further study. Avoid the phrase “future research is necessary” because the recommendation is too general to be helpful to readers. Instead, provide substantive and specific recommendations for future studies. Table 4 provides common discussion section pitfalls and recommendations for addressing them.

Follow the Journal’s Author Guidelines

After you select a target journal, identify the journal’s author guidelines to guide the formatting of your manuscript and references. Author guidelines will often (but not always) include instructions for titles, cover letters, and other components of a manuscript submission. Read the guidelines carefully. If you do not follow the guidelines, your article will be sent back to you.

Finally, do not submit your paper to more than one journal at a time. Even if this is not explicitly stated in the author guidelines of your target journal, it is considered inappropriate and unprofessional.

Your title should invite readers to continue reading beyond the first page [ 4 , 5 ]. It should be informative and interesting. Consider describing the independent and dependent variables, the population and setting, the study design, the timing, and even the main result in your title. Because the focus of the paper can change as you write and revise, we recommend you wait until you have finished writing your paper before composing the title.

Be sure that the title is useful for potential readers searching for your topic. The keywords you select should complement those in your title to maximize the likelihood that a researcher will find your paper through a database search. Avoid using abbreviations in your title unless they are very well known, such as SNP, because it is more likely that someone will use a complete word rather than an abbreviation as a search term to help readers find your paper.

After you have written a complete draft, use the checklist (Fig. 3 ) below to guide your revisions and editing. Additional resources are available on writing the abstract and citing references [ 5 ]. When you feel that your work is ready, ask a trusted colleague or two to read the work and provide informal feedback. The box below provides a checklist that summarizes the key points offered in this article.

figure 3

Checklist for manuscript quality

Data Availability

Michalek AM (2014) Down the rabbit hole…advice to reviewers. J Cancer Educ 29:4–5

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International Committee of Medical Journal Editors. Defining the role of authors and contributors: who is an author? http://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authosrs-and-contributors.html . Accessed 15 January, 2020

Vetto JT (2014) Short and sweet: a short course on concise medical writing. J Cancer Educ 29(1):194–195

Brett M, Kording K (2017) Ten simple rules for structuring papers. PLoS ComputBiol. https://doi.org/10.1371/journal.pcbi.1005619

Lang TA (2017) Writing a better research article. J Public Health Emerg. https://doi.org/10.21037/jphe.2017.11.06

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Acknowledgments

Ella August is grateful to the Sustainable Sciences Institute for mentoring her in training researchers on writing and publishing their research.

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Busse, C., August, E. How to Write and Publish a Research Paper for a Peer-Reviewed Journal. J Canc Educ 36 , 909–913 (2021). https://doi.org/10.1007/s13187-020-01751-z

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  • 16 April 2024

Structure peer review to make it more robust

peer review research paper template

  • Mario Malički 0

Mario Malički is associate director of the Stanford Program on Research Rigor and Reproducibility (SPORR) and co-editor-in-chief of the Research Integrity and Peer Review journal.

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In February, I received two peer-review reports for a manuscript I’d submitted to a journal. One report contained 3 comments, the other 11. Apart from one point, all the feedback was different. It focused on expanding the discussion and some methodological details — there were no remarks about the study’s objectives, analyses or limitations.

My co-authors and I duly replied, working under two assumptions that are common in scholarly publishing: first, that anything the reviewers didn’t comment on they had found acceptable for publication; second, that they had the expertise to assess all aspects of our manuscript. But, as history has shown, those assumptions are not always accurate (see Lancet 396 , 1056; 2020 ). And through the cracks, inaccurate, sloppy and falsified research can slip.

As co-editor-in-chief of the journal Research Integrity and Peer Review (an open-access journal published by BMC, which is part of Springer Nature), I’m invested in ensuring that the scholarly peer-review system is as trustworthy as possible. And I think that to be robust, peer review needs to be more structured. By that, I mean that journals should provide reviewers with a transparent set of questions to answer that focus on methodological, analytical and interpretative aspects of a paper.

For example, editors might ask peer reviewers to consider whether the methods are described in sufficient detail to allow another researcher to reproduce the work, whether extra statistical analyses are needed, and whether the authors’ interpretation of the results is supported by the data and the study methods. Should a reviewer find anything unsatisfactory, they should provide constructive criticism to the authors. And if reviewers lack the expertise to assess any part of the manuscript, they should be asked to declare this.

peer review research paper template

Anonymizing peer review makes the process more just

Other aspects of a study, such as novelty, potential impact, language and formatting, should be handled by editors, journal staff or even machines, reducing the workload for reviewers.

The list of questions reviewers will be asked should be published on the journal’s website, allowing authors to prepare their manuscripts with this process in mind. And, as others have argued before, review reports should be published in full. This would allow readers to judge for themselves how a paper was assessed, and would enable researchers to study peer-review practices.

To see how this works in practice, since 2022 I’ve been working with the publisher Elsevier on a pilot study of structured peer review in 23 of its journals, covering the health, life, physical and social sciences. The preliminary results indicate that, when guided by the same questions, reviewers made the same initial recommendation about whether to accept, revise or reject a paper 41% of the time, compared with 31% before these journals implemented structured peer review. Moreover, reviewers’ comments were in agreement about specific parts of a manuscript up to 72% of the time ( M. Malički and B. Mehmani Preprint at bioRxiv https://doi.org/mrdv; 2024 ). In my opinion, reaching such agreement is important for science, which proceeds mainly through consensus.

peer review research paper template

Stop the peer-review treadmill. I want to get off

I invite editors and publishers to follow in our footsteps and experiment with structured peer reviews. Anyone can trial our template questions (see go.nature.com/4ab2ppc ), or tailor them to suit specific fields or study types. For instance, mathematics journals might also ask whether referees agree with the logic or completeness of a proof. Some journals might ask reviewers if they have checked the raw data or the study code. Publications that employ editors who are less embedded in the research they handle than are academics might need to include questions about a paper’s novelty or impact.

Scientists can also use these questions, either as a checklist when writing papers or when they are reviewing for journals that don’t apply structured peer review.

Some journals — including Proceedings of the National Academy of Sciences , the PLOS family of journals, F1000 journals and some Springer Nature journals — already have their own sets of structured questions for peer reviewers. But, in general, these journals do not disclose the questions they ask, and do not make their questions consistent. This means that core peer-review checks are still not standardized, and reviewers are tasked with different questions when working for different journals.

Some might argue that, because different journals have different thresholds for publication, they should adhere to different standards of quality control. I disagree. Not every study is groundbreaking, but scientists should view quality control of the scientific literature in the same way as quality control in other sectors: as a way to ensure that a product is safe for use by the public. People should be able to see what types of check were done, and when, before an aeroplane was approved as safe for flying. We should apply the same rigour to scientific research.

Ultimately, I hope for a future in which all journals use the same core set of questions for specific study types and make all of their review reports public. I fear that a lack of standard practice in this area is delaying the progress of science.

Nature 628 , 476 (2024)

doi: https://doi.org/10.1038/d41586-024-01101-9

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Competing Interests

M.M. is co-editor-in-chief of the Research Integrity and Peer Review journal that publishes signed peer review reports alongside published articles. He is also the chair of the European Association of Science Editors Peer Review Committee.

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Reviewer comments: examples for common peer review decisions

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Peer-reviewing an academic manuscript is not an easy task. Especially if you are unsure about how to formulate your feedback. Examples of reviewer comment s can help! Here you can find an overview of sample comments and examples for the most common review decisions: ‘minor revisions’, ‘major revisions’, ‘revise and resubmit’ and ‘reject’ decisions.

Examples of ‘minor revisions’ reviewer comments

Examples of ‘major revisions’ reviewer comments, examples of ‘revise and resubmit’ reviewer comments, examples of ‘reject’ reviewer comments.

  • “This is a well-written manuscript that only needs to undergo a few minor changes. First, …”
  • “The manuscript is based on impressive empirical evidence and makes an original contribution. Only minor revisions are needed before it can be published.”
  • “I thoroughly enjoyed reviewing this manuscript and only have some minor requests for revision.”
  • “The authors develop a unique theoretical framework, and I believe that they should highlight their originality much more.”
  • “The authors conduct very relevant research, but fail to emphasise the relevance in their introduction.”
  • “The authors draw on extensive empirical evidence. I believe that they can put forward their arguments much more confidently.”
  • “The authors adequately addressed my feedback from the first round of peer review. I only have some minor comments for final improvements.”
  • “To improve the readability of the paper, I suggest dividing the analysis into several subsections.”
  • “Figure 3 is difficult to read and should be adjusted.”
  • “Table 1 and 2 can be combined to create a better overview.”
  • “The abstract is too long and should be shortened.”
  • “I had difficulties understanding the first paragraph on page 5, and suggest that the authors reformulate and simplify it.”
  • “The manuscript contains an elaborate literature review, but definitions of the key concepts are needed in the introduction.”
  • “Throughout the manuscript, there are several language mistakes. Therefore, I recommend a professional round of language editing before the paper is published.”
  • “The paper should undergo professional language editing before it can be published.”

If you want to learn more about common reasons for a ‘minor revisions’ decision and see examples of how an actual peer review might look like, check out this post on ‘minor revisions’ .

  • “The manuscript shows a lot of promise, but some major issues need to be addressed before it can be published.”
  • “This manuscript addresses a timely topic and makes a relevant contribution to the field. However, some major revisions are needed before it can be published.”
  • “I enjoyed reading this manuscript, and believe that it is very promising. At the same time, I identified several issues that require the authors’ attention.”
  • “The manuscript sheds light on an interesting phenomenon. However, it also has several shortcomings. I strongly encourage the authors to address the following points.”
  • “The authors of this manuscript have an ambitious objective and draw on an interesting dataset. However, their main argument is unclear.”
  • “The key argument needs to be worked out and formulated much more clearly.”
  • “The theoretical framework is promising but incomplete. In my opinion, the authors cannot make their current claims without considering writings on… “
  • “The literature review is promising, but disregards recent publications in the field of…”
  • “The empirical evidence is at times insufficient to support the authors’ claims. For instance, in section…”
  • “I encourage the authors to provide more in-depth evidence. For instance, I would like to see more interview quotes and a more transparent statistical analysis.”
  • “The authors work with an interesting dataset. However, I was missing more detailed insights in the actual results. I believe that several additional tables and figures can improve the authors’ argumentation. “
  • “I believe that the manuscript addresses a relevant topic and includes a timely discussion. However, I struggled to understand section 3.1.”
  • “I think that the manuscript can be improved by removing section 4 and integrating it into section 5.”
  • “The discussion and conclusions are difficult to follow and need to be rewritten to highlight the key contributions of this manuscript.”
  • “The line of argumentation should be improved by dividing the manuscript into clear sections with subheadings.”

If you want to learn more about common reasons for a ‘major revisions’ decision and see examples of how an actual peer review might look like, check out this post on ‘major revisions’ .

  • “I encourage the authors to revise their manuscript and to resubmit it to the journal.”
  • “In its current form, this paper cannot be considered for publication. However, I see value in the research approach and encourage the authors to revise and resubmit their manuscript.”
  • “ With the right changes, I believe that this manuscript can make a valuable contribution to the field of …”
  • “The paper addresses a valuable topic and raises interesting questions. However, the logic of the argument is difficult to follow. “
  • “The manuscript tries to achieve too many things at the same time. The authors need to narrow down their research focus.”
  • “The authors raise many interesting points, which makes it difficult for the reader to follow their main argument. I recommend that the authors determine what their main argument is, and structure their manuscript accordingly.”
  • “The literature review raises interesting theoretical debates. However, in its current form, it does not provide a good framework for the empirical analysis.”
  • “A clearer theoretical stance will increase the quality of the paper.”
  • “The manuscript draws on impressive data, as described in the methodology. However, the wealth of data does not come across in the analysis. My recommendation is to increase the number of interview quotes, figures and statistics in the empirical analysis.”
  • “The authors draw several conclusions which are hard to connect to their empirical findings. “
  • The authors are advised to critically reflect on the generalizability of their research findings.”
  • “The manuscript needs to better emphasise the research relevance and its practical implications.”
  • “It is unclear what the authors consider their main contribution to the academic literature, and what they envisage in terms of recommendations for further research.”

If you want to learn more about common reasons for a ‘revise and resubmit’ decision and see examples of how an actual peer review might look like, check out this post on ‘revise and resubmit’ .

  • “I do not believe that this journal is a good fit for this paper.”
  • “While the paper addresses an interesting issue, it is not publishable in its current form.”
  • “In its current state, I do not recommend accepting this paper.”
  • “Unfortunately, the literature review is inadequate. It lacks..”
  • “The paper lacks a convincing theoretical framework ,  which is necessary to be considered for publication.”
  • “Unfortunately, the empirical data does not meet disciplinary standards.”
  • “While I applaud the authors’ efforts, the paper does not provide sufficient empirical evidence.”
  • “The empirical material is too underdeveloped to consider this paper for publication.”
  • “The paper has too many structural issues, which makes it hard to follow the argument.”
  • “There is a strong mismatch between the literature review and the empirical analysis.”
  • “The main contribution of this paper is unclear.”
  • “It is unclear what the paper contributes to the existing academic literature.”
  • “The originality of this paper needs to be worked out before it can be considered for publication.”
  • “Unfortunately, the language and sentence structures of this manuscript are at times incomprehensible. The paper needs rewriting and thorough language editing to allow for a proper peer review.”

If you want to learn more about common reasons for a ‘reject’ decision and see examples of how an actual peer review might look like, check out this post on ‘reject’ decisions .

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  1. FREE 10+ Sample Peer Review Forms in PDF

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  2. 43 Great Peer Evaluation Forms [+Group Review] ᐅ TemplateLab

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  3. 50 Smart Literature Review Templates (APA) ᐅ TemplateLab

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  4. 30 Free Peer Evaluation Forms Templates

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  5. 43 Great Peer Evaluation Forms [+Group Review] ᐅ TemplateLab

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  6. My Complete Guide to Academic Peer Review: Example Comments & How to

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VIDEO

  1. Literature Review Template for Thesis/Proposal

  2. How to Make Table of Contents for Review Paper ?

  3. Systematic Literature Review Technique

  4. Reading research papers for your literature review #shorts #shortsfeed

  5. How To Write A Research Paper: Discussion (PROVEN Template)

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COMMENTS

  1. A step-by-step guide to peer review: a template for patients and novice reviewers

    The peer review template for patients and novice reviewers ( table 1) is a series of steps designed to create a workflow for the main components of peer review. A structured workflow can help a reviewer organise their thoughts and create space to engage in critical thinking. The template is a starting point for anyone new to peer review, and it ...

  2. How to write a peer review: practical templates, expert examples, and

    Read on for resources that will get you on the right track, including peer review templates, example reports and the Web of Science™ Academy: ... for a comprehensive and well-structured review, and help you comment on the quality, rigor and significance of the research paper. It will also help you identify potential breaches of normal ethical ...

  3. Peer Review Template

    Sample outline. Summary of the research and your overall impression. In your own words, summarize the main research question, claims, and conclusions of the study. Provide context for how this research fits within the existing literature. Discuss the manuscript's strengths and weaknesses and your overall recommendation.

  4. How to Write a Peer Review

    Think about structuring your review like an inverted pyramid. Put the most important information at the top, followed by details and examples in the center, and any additional points at the very bottom. Here's how your outline might look: 1. Summary of the research and your overall impression. In your own words, summarize what the manuscript ...

  5. PDF Peer Review Template

    Sample outline 1. Summary of the research In your own words, summarize the main research question, claims, and conclusions of the study. Provide context for how this research fits within the existing literature. Discuss t he manuscript's strengths and weaknesses and your overall recommendation. 2. Examples and evidence Ma j o r i ssu e s

  6. (PDF) A step-by-step guide to peer review: a template ...

    PDF | On Aug 1, 2021, Liz Salmi and others published A step-by-step guide to peer review: a template for patients and novice reviewers | Find, read and cite all the research you need on ResearchGate.

  7. What Is Peer Review?

    The most common types are: Single-blind review. Double-blind review. Triple-blind review. Collaborative review. Open review. Relatedly, peer assessment is a process where your peers provide you with feedback on something you've written, based on a set of criteria or benchmarks from an instructor.

  8. How to write a thorough peer review

    4. Other, lesser suggestions and final comments. Now, read your review carefully, and preferably aloud: if you stumble when reciting your own text, then readers will probably do the same. Reading ...

  9. How to Write a Peer Review: 12 things you need to know

    3) Skim the paper very quickly to get a general sense of the article. Underline key words and arguments, and summarise key points. This will help you quickly "tune in" to the paper during the next read. 4) Sit in a quiet place and read the manuscript critically. Make sure you have the tables, figures and references visible.

  10. PDF HOW TO WRITE AN EFFECTIVE PEER REVIEW REPORT

    PEER REVIEW REPORT GOAL: A peer review report has two purposes, and two different audiences. 1. To help the journal editor(s) decide whether a paper: a. falls within the scope of the journal b. is novel and/or significant enough in content to be published, and c. is clear and consistent enough in its presentation to be understood. 2.

  11. Step by Step Guide to Reviewing a Manuscript

    Step by step. guide to reviewing a manuscript. When you receive an invitation to peer review, you should be sent a copy of the paper's abstract to help you decide whether you wish to do the review. Try to respond to invitations promptly - it will prevent delays. It is also important at this stage to declare any potential Conflict of Interest.

  12. How to review a paper

    How to review a paper. A good peer review requires disciplinary expertise, a keen and critical eye, and a diplomatic and constructive approach. Credit: dmark/iStockphoto. As junior scientists develop their expertise and make names for themselves, they are increasingly likely to receive invitations to review research manuscripts.

  13. PDF A step- by- step guide to peer review: a template for patients and

    requiring peer reviewers with complementary expertise and training. Some experts may be highly equipped to critique particular aspects of research papers while unsuited to comment on other parts. Curiously, however, it Table 1 Peer review template for patients and other novice reviewers Name of journal Insert the name of the journal here

  14. My Complete Guide to Academic Peer Review: Example Comments & How to

    The good news is that published papers often now include peer-review records, including the reviewer comments and authors' replies. So here are two feedback examples from my own papers: Example Peer Review: Paper 1. Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine, J. Clark et al. 2020 - Available here

  15. A step-by-step guide to peer review: a template for patients and novice

    The peer review template for patients and novice reviewers is a series of steps designed to create a workflow for the main components of peer review. A structured workflow can help a reviewer organise their thoughts and create space to engage in critical thinking. ... Some experts may be highly equipped to critique particular aspects of ...

  16. (PDF) Quantitative manuscript peer review template

    This peer review collaborative template aims to address the growing need for structured peer. review combining all best practices and advice on peer reviews. The template has been pre-tested ...

  17. Peer Review Checklist

    Start with a summary of the research. State your overall impression. Number your comments and separate them into "major" and "minor" issues. Give concrete examples. Refer to specific sections and page numbers. Don't focus on spelling and grammar. Be professional and respectful.

  18. Peer Review Examples

    This paper by Amrhein et al. criticizes a paper by Bradley Efron that discusses Bayesian statistics ( Efron, 2013a ), focusing on a particular example that was also discussed in Efron (2013b). The example concerns a woman who is carrying twins, both male (as determined by sonogram and we ignore the possibility that gender has been observed ...

  19. Peer Review Templates

    The following templates propose criteria your students can use to assess their peers' work and to provide constructive open-ended feedback. Ideally, these criteria will reflect how you intend to grade. We have focused on two types of assignments: a writing-intensive assignment and a class presentation. Framing negatives as actionable ways the st...

  20. How to Write and Publish a Research Paper for a Peer ...

    Communicating research findings is an essential step in the research process. Often, peer-reviewed journals are the forum for such communication, yet many researchers are never taught how to write a publishable scientific paper. In this article, we explain the basic structure of a scientific paper and describe the information that should be included in each section. We also identify common ...

  21. Structure peer review to make it more robust

    In February, I received two peer-review reports for a manuscript I'd submitted to a journal. One report contained 3 comments, the other 11. Apart from one point, all the feedback was different.

  22. Reviewer comments: examples for common peer review decisions

    Examples of 'reject' reviewer comments. "I do not believe that this journal is a good fit for this paper.". "While the paper addresses an interesting issue, it is not publishable in its current form.". "In its current state, I do not recommend accepting this paper.". "Unfortunately, the literature review is inadequate.

  23. New Peer Review Framework for Research Project Grant and Fellowship

    Explore how scientific research by psychologists can inform our professional lives, family and community relationships, emotional wellness, and more. Popular Topics. ADHD; Anger; ... New Peer Review Framework for Research Project Grant and Fellowship Application. Peer Review; Funding and Grants; Live Webinar May 8, 2024. 1:00 PM, Eastern time.