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  1. 1. How to write a manuscript Get your paper accepted Society for Neuroscience San Diego, CA, USA November 14, 2010 Daniel McGowan, PhD Science Director Edanz Group Ltd / Liwen Bianji
  2. 2. Presentation  Introduction  Section One: Preparations before writing  Section Two: Manuscript structure  Section Three: Tips for getting accepted Edanz Group Japan | 2
  3. 3.  To share your research findings and opinions with the international research community  Publication success is linked to funding success and career advancement  Many PhD programs require candidates to achieve a set number of peer-reviewed publications Edanz Group Japan | 3 Why publish?
  4. 4. Funding Bodies Scientists / Clinicians Grant Writing Journal Publication Regularly publishing research findings ensures ongoing grant support for new research Publish or perish Edanz Group Japan | 4
  5. 5. Increased competition Edanz Group Japan | 5 0 200 400 600 800 1000 1200 1400 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 % Year Journal numbers Journal submissions Relative growth from 100% baseline in 1990
  6. 6.  How to identify hot topics  Study design  What do journal editors want?  Choosing an appropriate journal  Ethical issues Edanz Group Japan | 6 Section One Preparations before writing
  7. 7. Look for clues— unexplained findings, controversies Read the literature, including related fields Attend international meetings Greater interest = Greater competition Identify your advantages and use them How to identify hot topics Edanz Group Japan | 7
  8. 8.  Have a hypothesis or research question  Use appropriate methods and controls  Ensure sample sizes are large enough  Use appropriate statistical tests  Remove investigator/researcher/patient bias  Comply with ethical requirements Study design Get it right first time Edanz Group Japan | 8
  9. 9.  Can be the difference between success and rejection  What is the main focus of your research and who will be interested in it? (aims and scope, target audience)  What are its strengths and weaknesses? (impact factor)  How significant are your findings? (impact factor)  Are your findings preliminary or are they sufficient to make a story? (publication type)  How widely will your research appeal? To researchers in the same field or to the broader scientific community? (target audience) Journal Selection Edanz Group Japan | 9
  10. 10. Journal Selection Edanz Group Japan | 10 You have interesting and novel findings from well controlled experiments Rapid publication Check for relevant prior publications Your priorities Next step:Your research: Your research is preliminary but well enough developed to warrant publication Make sure you mention future research plans to expand on your current results High publication frequency Online publication within 10 days of acceptance Impact factor 2.494 Impact factor aim: Low to moderate but a good journal Aims and Scope Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure, function and chemistry at all levels of resolution, from molecular to behavioral and social that are of general interest to the broad community of neuroscientists.
  11. 11. Journal Selection Edanz Group Japan | 11 Your priorities Next step:Your research: Do you have mechanistic data to support any clinical data? Rapid publication Focus on neurology and neurological science Your research has a clinical focus or translational aspect Your target audience is neurologists You have interesting and novel findings from well controlled experiments Dedicated to rapid publication Clearly describe the clinical impact or translational potential of your findings Impact factor 9.49 Impact factor aim: High Aims and Scope Brain gives preference to definitive papers on neurology and related clinical disciplines. Brain publishes animal studies but requires that they demonstrate a novel approach, elucidate mechanisms underlying the observations made, and have substantial clinical relevance.
  12. 12. Unethical behavior could lead to rejection and a possible ban from a target journal. Multiple submissions Redundant publications Plagiarism Data fabrication and falsification Improper use of human subjects and animals in research Improper author contribution Publication ethics Edanz Group Japan | 12
  13. 13.  The ‘write’ order  Title  Abstract  Keywords  Introduction  Materials and Methods  Results  Display items  Statistics  Discussion and Conclusions  Acknowledgments  Abbreviations  References  Examples Section Two Manuscript structure Edanz Group Japan | 13
  14. 14. IMRaD manuscripts: for maximum clarity and consistency, write in this order:  Methods  Results  Introduction  Discussion  Title  Abstract Write after selecting your target journal Write during the research The ‘write’ order Edanz Group Japan | 14
  15. 15. Hook to catch readers Sells your manuscript to the editor Relevant readers increase citations Edanz Group Japan | 15 The importance of your title
  16. 16.  Convey the main findings of the research  Be specific and concise without focusing on only one part of the content  Avoid jargon, non-standard abbreviations and unnecessary detail  Comply with character limits  Some journals also require a short running title A good title should Edanz Group Japan | 16
  17. 17. Poor  Degeneration of neurons in the CA3 and DG following OA administration: involvement of a MAPK-dependent pathway in regional-specific neuronal degeneration Better  Region-specific neuronal degeneration after okadaic acid administration  MAP kinase-dependent neuronal degeneration after okadaic acid administration Edanz Group Japan | 17 A good title
  18. 18. Many researchers will only read the abstract so must be able to ‘stand alone’ Must give an accurate summary of your research, and enough information so that readers can understand: What you did Why you did it What your findings are Why your findings are useful and important Edanz Group Japan | 18 Abstract
  19. 19. General rules for abstracts:  Within the word limit  Avoid technical jargon  Avoid abbreviations unless necessary  Avoid references  Structured or unstructured? Always consult the target journal’s Guide for Authors to determine allowable length, style and abbreviations Edanz Group Japan | 19 Abstract
  20. 20. Keywords Edanz Group Japan | 20 Abstracts are usually followed by keywords:  Choosing appropriate keywords is important for indexing purposes → citations  Be specific to your manuscript  Avoid general terms  Many medical journal require MeSH (Medical Subject Headings) terms  Some journals do not allow keywords in the title
  21. 21. Manuscript title: Region-specific neuronal degeneration after okadaic acid administration Poor keywords: neuron, brain, OA (as an abbreviation), regional-specific neuronal degeneration, signaling Better keywords: neurodegenerative diseases; CA1 region, hippocampal; okadaic acid; neurotoxins; MAP kinase signaling system; cell death Edanz Group Japan | 21 Keywords
  22. 22.  Must give the reader enough background information to put your work into context  Enough information to understand the rationale for your study is all that is required  Do not write a comprehensive literature review of the field  Do cite reviews that readers can refer to if they want more information Edanz Group Japan | 22 Introduction
  23. 23.  Define technical and non-familiar terms  Present “the problem”, research question and/or hypotheses to explain the rationale for the study  Briefly explain how you addressed this problem and what was achieved (1–2 sentences for each)  Citations must be balanced, current and relevant Edanz Group Japan | 23 Introduction
  24. 24. Introduction A number of neurodegenerative diseases are associated with excitotoxic neuronal death [1]. However, the causes of nerve cell damage in these diseases have been hotly contested. The balance between kinase and phosphatase activity has been implicated in the pathogenesis of these diseases. The algal toxin okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, has been shown to cause hyperphosphorylationof tau, modification of synapse structure, destruction of stablemicrotubules, and apoptosis in neurons [2]. It also kills a variety of cell types in culture, with disruption of the cell cytoskeleton [3]. Because OA induces neurodegenerative disease- like phenotypes in animals, it is often used to model these disorders [4]… However, although components of the MAP kinase signaling pathway have been implicated, the mechanism of this action of OA in neurons has remained unknown. In the current study, we investigated the signaling pathways affected by OA treatment in vitro, and the areas of the brains of male Wistar rats that were preferentially damaged by OA treatment, using hippocampal slice culture. We found that hippocampal cells, in particular, underwent non-apoptotic cell death via a MAP kinase-dependent mechanism. Edanz Group Japan | 24 Region-specific neuronal degeneration after okadaic acid administration Daniel P McGowan, Thomas da Costa, Richard Parris, Benjamin Shaw and Kerry A Greer Statement of the problem Background Rationale What was done and found
  25. 25.  Clear subheadings for methods/materials  Describe methods in the past tense  Novel methods must be described in sufficient detail for a capable researcher to reproduce the experiment  Give manufacturers/suppliers and their locations  Describe any statistical tests used  Established methods can be referenced Edanz Group Japan | 25 Materials and methods What you did
  26. 26. Methods and Materials Materials. Culture media were obtained from Life Technologies (Gaithersburg, MD). Okadaic acid was purchased from Alexis Company (Läufelfingen,Switzerland). Antibodies to MEK1/2 and phosphorylated MAPK were purchased from New England Biolabs (Beverley, MA). Induction of cell death. Cell death was induced as described previously [15]. Briefly, cell death was induced by adding okadaic acid (0-300 nM, Alexis Co.) after washing slice cultures in serum-free medium. Light and electron microscopy. Cultures were fixed in 2.5% glutaraldehyde and 1% formaldehyde, treated with 1% OsO4 in 0.1 M phosphate buffer, pH 7.4, dehydrated in a graded series of ethanoland propylene oxide, and flat- embedded in an epoxy resin (DurcupanACM, Fluka, Neu-Ulm, Germany). Semithin sections were stainedwith toluidine blue, and ultrathin sections were stained with 1% uranyl acetate for 20 min and 1% lead citrate for 2 min. Statistics. For statistical analysis, 2-tailed Student’s t test was used to assess the significance of mean differences. Differences were considered significant at a P value of 0.05 or less. Edanz Group Japan | 26 Region-specific neuronal degeneration after okadaic acid administration Daniel P McGowan, Thomas da Costa, Richard Parris, Benjamin Shaw and Kerry A Greer Materials described first Suppliers/locations given Clear subheadings Refs used to save space Enough information to reproduce the experiment Statistical test parameters provided
  27. 27.  Assemble your findings in a logical order to ‘make a story’  Present your findings in subsections (the same as those in your methods section)  Present complementary evidence when possible  Describe results in the past tense  Refer to figures and tables in the present tense  Do not discuss implications — do that in the discussion section  Do not duplicate data among figures, tables and text  Show the results of statistical analyses, (e.g., p values) Edanz Group Japan | 27 Results What did you find?
  28. 28. Results Okadaic induces death of dentate gyrus neurons selectively. Hippocampal slice cultures treated with OA (1–300 nM) showed selective cell death of neurons in the dentate gyrus, but neurons in the CA1–3 regions were largely unaffected. Cell death occurred in a time- and dose-dependent manner. Propidium iodide staining of treated slides indicated…. Electron microscopy revealed a number of ultrastructural changes in hippocampal pyramidal neurons, particularly those in the CA3 region, in slices treated with 300 nM OA for 24 h (Fig 3). These changes included slight nuclear aggregations (arrow in Fig 3A), accumulation of mitochondria around nuclei (arrowheads in Fig 3B) and an increased amount of endoplasmic reticulum (Fig 3C). As shown in Figure 4, the nuclei of pyramidal neurons in the CA1 and CA3 regions… Involvement of MAPK signaling in the effect of OA. Compared with slices treated with medium only and treated slices at 0 h, slices treated with 300 nM OA showed increasing levels of phosphorylated MAPK at 4 h, 8 h, 16 h and 24 h, with no corresponding change in the levels of total MAPK. This increase was prevented in slices that were co-incubated with a protein kinase inhibitor. In addition, the levels of phosphorylated Tau were higher in OA-treated slices than in control slices… Edanz Group Japan | 28 Region-specific neuronal degeneration after okadaic acid administration Daniel P McGowan, Thomas da Costa, Richard Parris, Benjamin Shaw and Kerry A Greer Clear subheadings Graphics used to save space Clear comparisons made
  29. 29.  Some readers will only look at the figures and their legends so they must stand alone  Figures and tables are the best way to present your results concisely  Data shown in figures and tables must be easy to interpret — use separate panels if necessary  Clearly label all components  Show trendlines, scale bars and statistical significance  Legends must be able to ‘stand alone’  Comply with journal guidelines on display items Edanz Group Japan | 29 Display items Tables and figures
  30. 30. Tables are a great way to present large amounts of necessary data with minimal description required Edanz Group Japan | 30 Display items Tables and figures Clear concise heading Data divided into categories for clarity Abbreviations defined
  31. 31. Edanz Group Japan | 31 Display items Tables and figures Clear, ‘stand alone’ legend Scale bars Significance indicated Clear labels Arrows
  32. 32. Edanz Group Japan | 32 Display items Tables and figures Illustrations are a great way to convey anatomy or a proposed model
  33. 33. Edanz Group Japan | 33 Statistics A man has one hand in boiling water… The other hand in freezing water… He is comfortable—on average…
  34. 34. Statistical analysis is at the heart of scientific inquiry Consider statistical analysis when you design your study. Before you start your research. Edanz Group Japan | 34 Statistics Data collection Data analysis Interpretation
  35. 35. Edanz Group Japan | 35 Statistics Poor statistics Poor statistics Poor study design e.g., sample size is too small Poor analysis Data are valid Re-analysis or re-interpretation Revise manuscript Difficult to recover… Poor interpretation
  36. 36. Edanz Group Japan | 36 Statistics Questions Ask yourself these questions during study design: What are the independent and dependent variables? What is the scale of measurement of the study variables? Consider sample number for power analysis i.e., how many samples will you need? Have I met the assumptions of the statistical test selected?
  37. 37. Reporting statistics in your manuscript:  Consult a statistical expert about which test to use!  Clearly describe the statistical tests used to analyze data  Give the software, version number and maker  Indicate the parameters described, e.g., “means±S.D”  Only use the word “significant’ when describing statistically significant differences  Report p values, e.g., use “p=0.0035” rather than “p<0.05” Edanz Group Japan | 37 Statistics Basics
  38. 38. Restate your research question and/or any hypotheses presented in the introduction Summarize your main findings—make it clear how your study has advanced the field Begin with your most important finding Past tense to describe results (current and published) Present tense to describe their implications Minimize repetition with other sections Describe inconsistencies with other papers Describe the limitations of your study Edanz Group Japan | 38 Discussion What does it all mean?
  39. 39. Be humble Don’t overstate the importance of your results Our findings prove that… Our findings show that… Our findings suggest that… Edanz Group Japan | 39 Discussion
  40. 40.  Restate key findings and their significance  Propose future studies that might follow on from your current study  Give the reader a ‘take-home’ message Edanz Group Japan | 40 Conclusions “ …we can now conduct quantitative and functional genetic studies in natural populations” (Science) “Further, the structures reported here highlight the complex network of protein- protein and protein-DNA interaction…” (Nature)
  41. 41. Discussion The mechanisms underlying the excitotoxic neuronal cell death observed in a variety of neurodegenerative diseases have remained unclear, despite a large number of hypotheses being put forward. The neurotoxin OA induces neurodegenerative disease-like phenotypes and non-apoptotic cell death in animals. We investigated the signaling pathways involved in induction of this form of cell death in hippocampal slice cultures obtained from…. We observed selective neuronal cell death of dentate gyrus neurons in hippocampal slice cultures treated with OA (1–300 nM), occurring in a time- and dose-dependent manner. Neurons in the CA1–3 regions were relatively spared. However, electron microscopy revealed ultrastructural changes in pyramidal neurons in the CA3 region… These findings suggest that DG neurons in the hippocampus are particularly sensitive to OA, supporting the results of Wysong et al. [11] who described cell loss in the DG region of mice treated with OA. In contrast to the findings of Yim et al., who studied cultured Neuro2A cells, we observed a significant increase in the levels of phosphorylated MAPK in slices treated with OA. This difference could be due to the fact that…. In conclusion, by treating hippocampal slice cultures with OA and a variety of kinase and phosphatase inhibitors, we show that the excitotoxic cell death induced by this neurotoxin depends on MAPK activation and subsequent signaling. Future work should investigate the effects of protein kinase inhibitors on preservation of learning and memory functions in animals treated with OA. Edanz Group Japan | 41 Region-specific neuronal degeneration after okadaic acid administration Daniel P McGowan, Thomas da Costa, Richard Parris, Benjamin Shaw and Kerry A Greer Briefly restate the question or problem Restate main findings Put in context of previous work Concluding paragraph with future directions
  42. 42.  Always format your references: check your target journal’s Guide for Authors for the appropriate format Harvard style or Vancouver style or APA  Formatting is required both in text and in the references section  Use a reference manager like Endnote. Makes it easy to edit, reformat, add or remove references  Some journal limit the number of references: check your target journal’s Guide for Authors Edanz Group Japan | 42 References
  43. 43. References Edanz Group Japan | 43 Pay attention to reference style in text: Insect hunting is an ideal way to study predatory behavior (Suzuki et al., 2005). Insect hunting is an ideal way to study predatory behavior (Tanaka and Honda). Insect hunting is an ideal way to study predatory behavior [1]. Insect hunting is an ideal way to study predatory behavior (1). Insect hunting is an ideal way to study predatory behavior. [1,2] Insect hunting is an ideal way to study predatory behavior [1–3]. Insect hunting is an ideal way to study predatory behavior.¹ Tanaka reported that insect hunting was an ideal way to study predatory behavior (2005).
  44. 44. Your cover letter Recommending reviewers Language Good writing Common language problems What do reviewers look for? Submission Final checks Post-referee revisions Checklist Section Three Tips for getting accepted Edanz Group Japan | 44
  45. 45. Cover letters Edanz Group Japan | 45 Journal Editors receive hundreds of manuscripts each month They don’t have time to read each manuscript Society journal editors are especially busy as they are usually practicing researchers too Your cover Letter is an opportunity to get the journal editor’s attention
  46. 46. Competition for publication space and for editors’ attention is very high It is not enough to send a manuscript to a journal editor like this: Cover letters Edanz Group Japan | 46 Dear Editor-in-Chief, I am sending you our manuscript entitled “Large Scale Analysis of Cell Cycle Regulators in bladder cancer” by A. Honda, K. Tanaka, J. Suzuki, and myself. We would like to have the manuscript considered for publication in Pathobiology. Please let me know of your decision at your earliest convenience. With my best regards, Sincerely yours, Shinsuke Izumi, PhD
  47. 47. General rules for cover letters: Address to the editor personally Begin by giving your manuscript title and publication type Give a brief background, rationale and description of the results Explain why your findings are important and why they would be of interest to the journal’s target audience Consult the journal’s Guide for Authors for cover letter requirements (e.g., disclosures, statements, potential reviewers) Give corresponding author details Your cover letter Edanz Group Japan | 47
  48. 48. Dear Dr Lisberger, Please find enclosed our manuscript entitled “Amyloid-like inclusions in the brains of Huntington’s disease patients”, by McGowan et al., which we would like to submit for publication as a Research Paper inNeuroscience. Recent immunohistochemical studies have revealed the presence of neuronal inclusions containing an N-terminal portion of the mutant huntingtin protein and ubiquitin in the brain tissues of Huntington’s disease (HD) patients; however, the role of these inclusions in the disease process has remained unclear. One suspected disease-causing mechanism in Huntington’s disease and other polyglutamine disorders is the potential for the mutant protein to undergo a conformational change to a more stable anti-parallel β-sheet structure… To confirm if the immunohistochemically observed huntingtin- and ubiquitin-containing inclusions display amyloid features, we performed Congo red staining and both polarizing and confocal microscopy on post-mortem human brain tissues obtained from five HD patients, two AD patients, and two normal controls. Congo red staining revealed a small number of amyloid-like inclusions showing green birefringence by polarized microscopy, in a variety of cortical regions.... ….detected inclusions observed in parallel sections, suggesting that only a relatively small proportion of inclusions in HD adopt an amyloid-like structure. We believe our findings would appeal to a broad audience, such as the readership ofNeuroscience. As a wide-reaching journal publishing original research on all aspects of neuroscience… We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with submission toNeuroscience. We have read and have abided by the statement of ethical standards for manuscripts submitted to Neuroscience. The authors have no conflicts of interest to declare. Please address all correspondence to…. Background What was done and what was found Why this is interesting to the journal’s readership Conforms to the journal’s requirements Your cover letter Edanz Group Japan | 48 Addressed to editor Title and publication type provided Correspondence information
  49. 49. Journal editors are overloaded with quality manuscripts. They may make decisions on manuscripts based on formal criteria, like grammar or spelling. Don't get rejected for avoidable mistakes: make sure your manuscript looks perfect Language Edanz Group Japan | 49 A senior executive at a large international publishing house Spelling errors are a sign of sloppiness, and a sloppy manuscript implies sloppy research A journal’s instructions for authors
  50. 50. Introduction of language screening protocols to check submissions  Editors don’t want to send poorly written manuscripts for peer review  Editors receive enough well written submissions to reject poorly written manuscripts Language screening Edanz Group Japan | 50
  51. 51. Clarity Conciseness Correctness (accuracy) Good scientific writing possesses the following three “C”s: Key points: Be as brief as possible without omitting essential details Be as specific as possible Scientific writing Edanz Group Japan | 51
  52. 52. Avoid: Spelling and grammatical errors Insufficient detail/vagueness Repetition Redundancy Ambiguity Inconsistency They annoy editors, peer reviewers and readers Scientific writing Common problems Edanz Group Japan | 52
  53. 53. Tense Articles Plural or singular Proper nouns Hyphen or dash That/which Making comparisons Respectively Between or among Nomenclature Such as/namely Etc. Asian fonts UK or US spelling Presenting numbers Language Common English problems Edanz Group Japan | 53
  54. 54. Use simple language: it is often clearer, more precise and more concise than using more complex language Say what you mean in as few words as possible Delete unnecessary words Avoid circular sentences, redundancies and repetition One sentence: one idea Simple is best Edanz Group Japan | 54
  55. 55. Is the manuscript sufficiently novel? Is the manuscript of broad enough interest? Reviewers What do they look for? Edanz Group Japan | 55 Novelty Significance Aims and Scope Impact Factor
  56. 56. The research question is not interesting Are the methods used appropriate? Are any additional experiments/analyses necessary? Are the statistical tests used appropriate? Are all possible interpretations of the data considered? The data does not support the conclusion Reviewers About the research Edanz Group Japan | 56
  57. 57. Reviewers About the manuscript Edanz Group Japan | 57 Are the rationale and objectives defined? Is enough background given to understand the rationale? Could a capable researcher reproduce the experiments? Are the results clearly explained and in the best format? Are the findings described in context? Are the limitations discussed? Are the conclusions supported? Is the literature cited appropriate? Are there contradictions within the manuscript?
  58. 58.  Critically self-evaluate—could anything be done better?  Double check the Guide for Authors  Are all files in the correct file format and of the appropriate resolution or size?  Is your spelling/grammar correct?  Do you have contact information for all authors and have they all approved the manuscript and target journal?  Have you written a persuasive cover letter? Submission Final checks Edanz Group Japan | 58
  59. 59. Rejection from journals is an important part of the publication process It is not a negative experience It exists to ensure that your paper is as scientifically robust and complete as possible before joining the ‘collective knowledge’ as part of the literature Revisions Post-referee revisions Edanz Group Japan | 59
  60. 60. Only 1.5% of papers are immediately accepted without need for any revisions Journal editor decision Complete rejection Acceptance Rejection with major revisions Rejection with minor revisions Revisions Post-referee revisions Edanz Group Japan | 60
  61. 61. Edanz Group Japan | 61 Response Letter Say “thank you” to each reviewer Be polite Perform the requested additional experiments/analyses if possible: they will make your paper stronger If you disagree with a reviewer, say why Provide scientifically valid reasons in your rebuttal Respond to every comment Return within the stated deadline or it will be considered a new submission
  62. 62. Edanz Group Japan | 62 Response Letter Common phrases Explain any big structural changes: Clearly indicate, which reviewer and which point you are responding to: Add page and line numbers to make it easy to locate changes: Clearly differentiate between Comments and Responses: E.g., “We removed table 1 and replaced Figure 3” E.g., Reviewer 1, comment 3: example example… Response: example example… Reviewer comment Response Reviewer comment Response Deletions in strike through font Additions in fonthighlighted E.g., “Please see page 4, line 19–21”
  63. 63.  Work in an area of interest  Appropriate study design  Compliance with ethical guidelines  Appropriate statistical tests  Novel and interesting results  Appropriate choice of journal  Clear, concise, accurate writing  Compliance with the Guide for Authors  Significance of findings clearly explained Summary Checklist for acceptance Edanz Group Japan | 63