Making An English Biomedical Paper: Why, What, and How

Making An English Biomedical Paper: Why, What, and How
发表英文医学论文技巧 Ruiwen Zhang, MD, PhD, DABT 张瑞稳博士 Professor, Pharmacology and Toxicology Director, Cancer Pharmacology Laboratory Sr. Scientist, Comprehensive Cancer Center, Clinical Nutrition Research Center, Chemoprevention Center, Gene Therapy Center, Center for Aging, & Center for AIDS Research University of Alabama School of Medicne Birmingham, AL 35294, USA Editor-in-Chief 美捷登主编

Obligations of a Scientist
Accomplish technically competent, thorough, and ethical research Employ objective scientific judgment and seek appropriate advice. Publish honest reports in a timely fashion. Session 1

Benefits of Writing To think more clearly.
To fulfill the responsibility to report and share information with the scientific community. To produce a final product of a successful research project. To achieve personal gain, establish oneself as an expert, and receive grants and promotions. Publications are the currency of the world of science. Session 1

Types of Scientific Writing
Not public Public Peer-reviewed Original research papers Reviews Meeting abstracts Conference reports Grant Applications Fellowship proposals Books, chapters Book reviews Teaching materials Theses/dissertations Editorial comments Letters to the editor Research reports (sometimes) Web pages Not peer-reviewed Correspondence Confidential reports Session 1

Enumeration/Illustration Cause-effect
Major Techniques in Scientific Writing Definition Compare-contrast Enumeration/Illustration Cause-effect Session 1

Characteristics of Scientific Writing (1)
English: the universal language of science - Eugene Garfield, 1987 Reader-oriented ---- Sharing information Three Things to Avoid Laboratory jargon Invented words Non-standard abbreviations Purposeful ---- Convey information, ideas, concepts Precise ---- Choose words meant to be said Accurate ---- Conformity, actual (true) state Session 1

Characteristics of Scientific Writing (2)
Clear Reaches the audience with the same meaning it had Should NOT be interpreted in more than one way ---- Avoid When something is said for the first time, clarity is essential. Concise Expresses, covers much in few words The best English is that which gives the sense in the fewest short words. – Instructions to Authors, Journal of Bacteriology. Simple ---- Easy to understand, not elaborate or artificial, not ornate, not complicated Illustrated “A picture is worth a thousand words.” Make use of good figures and tables Session 1

Sins of Language Session 1 excess omission Misunderstanding Misleading
Harm dishonesty ignorance malice Session 1

Characteristics of a Valid Manuscript (1)
First report of the data (original paper) Original research results (not me-too) Allow peers to repeat the reported experiments (not necessarily the results) Publish in a journal or other public source document Available to the scientific community Be received and understood Session 1

Characteristics of a Valid Manuscript (2)
Characteristic format ---- IMRAD (Introduction, Methods (& Materials), Results, and Discussion) Introduction: What question was studied? Methods: How was it studied? Results: What were the findings? Discussion: What do the findings mean? This logic helps the author organize and write the manuscript. Traditional format Cancer Research PNAS USA Alternative format: Introduction, Results, Discussion, and Methods (& Materials) EMBO J Oncogene Letter format Nature Science Session 1

Completion of Experiments
Overview: The Research Process Hypothesis Submit the Manuscript Prepare a Final Draft Prepare a Revised Draft Prepare a Draft Prepare an Outline Revise the Hypothesis Completion of Experiments and Data Analysis Experimental Design Session 1

Overview: The Publication Process
Submit the Manuscript Assignment and Peer Review Editorial Decision Rejection Revision Acceptance Publication Rebuttal The Research Process Resubmission Re-review Session 1

Ten (10) Key Questions Session 1 Is there a story to tell?
What was the rationale for the project? Did I perform a thorough literature review? What is the historical context of the work? Did I have a clear hypothesis? Did the experiments test that hypothesis? Is the experimental design defendable? Can I justify what I did? Did I use appropriate controls? How do my findings relate to the existing knowledge? Session 1

Why and How to Publish (1)
Scientists ---- building a career (not just publish a paper) Intense competition for space in journals High cost of publication ( ~$300 per page) Rejection rates vary, e.g., JBC = 75%; NEJM, Science, Nature = 90%) Perform laboratory work with a manuscript in mind (Design a paper) Scientific writing involves work Session 1

The first publication on a specific topic has priority. The findings should be expressed as simply as possible. Succinct, concise, “crisp,” and terse, i.e., brief and to the point. You are NOT writing a novel. Sentences should be stripped to their “bare bones.” Writing requires: Perseverance Self discipline Orderly thinking Writing is best accomplished in a quiet place, in a straight-backed chair, and in good lighting. (Once again, writing involves WORK; you need an excellent writing environment.) Session 1

Present substantial, fresh, relevant information (A manuscript is worthless if the authors have nothing worth reporting) Write what you know Good writing comes from good thinking Word power comes from intelligent reading Thinking Reading Writing Session 1

Write too much and then make deletions. Be brief. “Brevity is the soul of wit.” – Shakespeare. Do not publish several articles when one will suffice Do not publish similar articles with minor changes. Allow trainees to develop their own style, while maintaining quality control. To learn what works: Read more Write more Review more Your reputation can be affected by a poor publication. If you have a reputation for scientific honesty and careful writing, editors and readers may give you the benefit of the doubt. Session 1

Steps in Writing a Manuscript (1)
Reading Thinking Writing Revising Q: Professional Writing Service? Session 1

Search and Review the Literature: Use MEDLINE + other sources Search using all appropriate keywords Summarize relevant points of related articles Prepare an Outline Preparation forces you to think and organize. All points should be supported by appropriate data. Gives a logical, step-by-step order in which the manuscript will be presented. Gaps can be filled in, and extraneous material can be eliminated. Writing can be done with less interruption. Session 1

Checklist for Preparing an Outline
Ensure that you are up-to-date on the literature in the field Confirm that the results are “real”- i.e., they cannot be explained by experimental error and have been repeated Complete the initial statistical analyses Select a target journal Look over the “Instructions for authors” Decide on the authors, and decide who will be the corresponding author Verify the current institution and address for each of the authors Decide who will be responsible for the various parts of the manuscript: Introduction:_________________Methods/Materials:___________________ Results:____________________Discussion:__________________________ Figures:____________________Tables:_____________________________ References:_________________Overall formatting:____________________ Discuss who will be responsible for other parts of the submission process Cover letter:_________________Online/mail submission:________________ Revisions:___________________Letter for revision/rebuttal:_____________ Determine who should be included in the acknowledgements Select a targeted date for submission Select major references to be cited Make a list of the procedures and instruments used, along with the conditions for each experiment Verify the details of the experiments (cell culture conditions, age of animals, duration of treatments, doses of agents used, etc.) Prepare the figures and tables for the major data that you will present Prioritize the data (The most important? Supporting Data? Supplemental data (if applicable for the selected journal)?) Session 1

Sample Outline Session 1 Introduction
Epidemiological studies show a correlation between isoflavone consumption and cancer. Evidence supports the idea that genistein is the most important isoflavone in the diet. Genistein has an anticancer effect in animal models. Main Point: Epidemiological studies show that diet, which can vary substantially from one country to another, is one of the major factors in cancer etiology and may account for up to 35% of the differences in cancer rates among different countries. Thesis Statement: Genistein, a dietary component, has a novel mechanism of action, whereby it specifically down-regulates MDM2 at both transcriptional and post-translational levels. Materials and Methods: Plasmids and reagents Cell lines and cell cultures Reverse transcription-PCR Assays for apoptosis, cell proliferation, cell cycle distribution, and clonogenicity Xenograft models Results: Genistein inhibits MDM2 expression in human cancer and primary cell lines, regardless of p53 status. (Figures 1 and 2) MDM2 transcription is repressed by genistein. (Figure 3) Genistein promotes degradation of the MDM2 protein, independent of p53. (Figure 4) Inhibitory effects of genistein on tyrosine kinases are not required for the down-regulation of MDM2. (Figure 5) Genistein has antitumor effects on apoptosis, cell cycle distribution, and cell proliferation, regardless of cellular p53 status. (Figure 6) In vitro antitumor activities of genistein are associated with its capacity to down-regulate MDM2. (Figure 7) In vivo MDM2 inhibition by genistein shows dose-dependent antitumor activity and chemosensitization, independent of p53. (Figure 7) Discussion: Reason for interest in genistein. Purpose of study and summary of results. Transcriptional activation of MDM2. NFAT, a specific transcription factor. Post-translational regulation of the MDM2 protein. Lack of effect of tyrosine kinase inhibitors. Importance of MDM2 expression in cancer. The antitumor effect of genistein and its effect on MDM2. Conclusion: Importance of results in relation to cancer prevention and therapy. Session 1

Actual Writing (Turtle or Rabbit Writer?): General Approach to generating first draft: Tables and Figures Results Methods Introduction Discussion Abstract Title References Other parts General Approach to Revising first draft: Read the First Draft (From the beginning to the end Read it again Read literature again Revise Introduction, Results and Discussion Methods Abstract Title Title and other parts Session 1

Actual Writing (Turtle or Rabbit Writer?): General Approach to Revising 2nd and nth drafts: 2nd Complete Draft Send to all authors Nth Draft Semi-final version Send to Outside reader/consultant/editing service Final version General Approach to preparing the final version: Reading, reading, reading Checking, checking, checking Submission package Cover letter Suggested reviewers, if needed Submission Approve submission Waiting for the news Session 1

Select an Appropriate Journal (1)
Target Journal Have a journal in mind as you design and perform your experiments. Basis for selection of a target journal: Who is the target audience? General Multidisciplinary Specific How important is the contribution? If it is “earth-shaking” and of interest in several scientific fields or if it is a major advance in a particular discipline, submit the manuscript to Nature, Science, Cell, or PNAS. Not Sure? Ask a trusted colleague! Session 1

SCI and Impact Factor What is the impact factor of the journal? Calculation for journal impact factor: Example: Nature 2007 Impact Factor Cites in 2007 to articles published in: 2006 =25635 =32644 Sum: Number of articles published in: =962 2005 =1065 Sum: 2027 Calculation: /2027=28.751 Session 1

SCI and Impact Factor Myths of Impact Factors (IFs): IFs do not reflect the quality of individual papers. Review journals generally have higher IFs. IFs are biased against specialty, clinical research or new fields of research. Not all journals are included in the index. IFs can be manipulated by editors/publishers. IFs fluctuate year to year for a given journal. Journals originated from Non-English country generally have lower IFs IFs cannot be used to compare publications in different fields (subject category) Simple math does not work here: IF 10 = IF1 X10? IF 5+ IF5 =IF10? IF 10X 6= IF60? IF is better than IF 5.613? Session 1

Major Secondary Services Is it recognized by one or more of the major secondary services (Chemical Abstracts, Biological Abstracts, MEDLINE/PubMed)? MEDLINE (Medical Literature Analysis and Retrieval System Online) is an international literature database of life sciences and biomedical information. It covers the fields of medicine, nursing, pharmacy, dentistry, veterinary medicine, and health care and much of the literature in biology and biochemistry. (~5000 serials) PubMed is a free search engine offering access to the MEDLINE database of citations and abstracts of biomedical research articles. It also provides access to many pre-1966 publications. CA (Chemical Abstracts Service), a division of the American Chemical Society, produces Chemical Abstracts, an index of the scientific literature in chemistry and related fields. (~9500 serials) Biological Abstracts directs users to information on life science topics, ranging from botany to microbiology to pharmacology. (>3700 serials) Session 1

More than IF What is the prestige of the journal? Is it a primary journal? Is it an open journal? What is the circulation of the journal? What is the review time for the journal? What is the publication time for the journal? Most Journals publish the dates of submission, review, and acceptance. You need to check the publishing date: Epub ahead of print; In press MS; Open access; online only; PubMED submission; etc. Session 1

More than IF Who will be interested in reading the paper – basic scientists, clinicians, or both? Whom do you want to read the paper – members of the funding committee, the promotion committee, or the competitors? Is the paper within the “Scope” of the journal (in the “Instructions for Authors” ). Be familiar with the journal, especially papers published in the last 6-12 months Still not sure: Ask a trusted peer, and, if possible, be acquainted with the editor. Session 1

Knew What You Wish For Check recent articles in various journals; examine their format and content. Examine several articles in potential journals. How many figures and tables do they have? Read the “Table of Contents” of recent issues of potential journals. Consider: Am I qualified to write an article for this journal? Consider: Where were the papers you will cite as references published-were they published in a similar quality journal? Read the “Instructions for Authors” and examples of publications in these journals. Keep in Mind: Topic, Contents, Format, and Style. Session 1

Wrong Journal or Wrong Paper? If you submit to a wrong journal: Your manuscript may be returned to you without review. It may be reviewed inadequately. Its publication may be unnecessarily delayed. Your work may remain unknown because it is not read after publication. Still not sure: Ask the Editor of the potential journal. Do not overly depend on ‘Professional Editing Service” Session 1

Data Preparation and Evaluation (1)
Checklist for finalizing data for a manuscript Make sure your results have been repeated/confirmed Select results that are representative of your repeats (for Western blots, photographs, spectra, etc) or prepare averages and standard deviations for your data (clinical parameters, animal studies, etc.) Ensure that your data are statistically significant, and that you indicate this in the text and figures. Prepare an appropriate number of figures and/or tables (many journals have a limit of 6 figures) Confirm that your figures and tables are supported by raw data Make sure that the raw data is retrievable (in laboratory records) Organize data by importance (key data, supporting evidence, and/or supplemental data) Determine they type of illustration that will best showcase the data (Figure? Table? Photograph?) Generate figures of sufficient quality for your selected journal (journals frequently require figure quality of 600 dpi) Format your illustrations according to the instructions for authors (font style and size) and, if possible, use a consistent size and style for each figure and table Avoid redundancy between tables, figures and the text The corresponding author needs to check the quality and accuracy of the data, and that the data is supported by raw data The figures and tables should indicate statistical significance (if applicable) Prepare supplemental illustrations (if applicable for your journal) Write figure and table legends (the legends should describe the figure and methods in sufficient detail so that the reader knows what the data indicate and how they were obtained) Check all the materials and methods and/or key references Session 1

Q: Do I need All the data before beginning the writing No But You need All Key data Most supporting data Some supplemental data You need ALL the data before the completion of the first draft You still can add data before final submission You should evaluate your data periodically and prepare your outline and key data as soon as possible. Session 1

Q: Who should evaluate and check the data? All the authors Key persons Primary authors Corresponding author(s) Technical staff Collaborators You may ask trusted colleagues to evaluate the data Hot topic: Can you trust the internet to send your unpublished data? Session 1

Q: Does the format of the data presentation matter? Yes You can present your data in various manners Table Simple Complex Number of the tables Figure Color? Number of the figures Number of panels in a figure Text The best way is to use all the above, but not redundant Hot Topic: The art of scientific data presentation Session 1

Q: Why is statistical analysis so important? The following statements are frequently based on statistical analysis: Significant Effective Correlation/relation Causal relation Safe Better or Worse Confirm or rule out a hypothesis Prediction/Extrapolation Other You Almost Always need help from a statistician, from planning to design to analysis to reporting It is almost too late if the reviewer/editor requests statistical analysis for your paper. Hot topic: You should know the difference between “statistical significance” and “biological significance”. Session 1

Session 1 Summary Publish or Perish Publish or Not Publish
SCI and beyond Personal vs Public Individual vs Team Quality vs Quantity Reading, Reading, Reading Thinking, Thinking, Thinking Writing, Revising, Revising Know yourself: Turtle or Rabbit Key to Success: Seeking Advice

发表英文医学论文技巧 Session 2 Writing Tips for Major Sections

General Order of Writing (1st Draft)
Selecting and Finalizing Data Results Materials and Methods Introduction Discussion Title References Abstract Other sections Session 2

Introduction/Background (1)
Every Paper needs an Introduction section Original Article Review Article Case Report Technical/Method Report Letter Editorials Other This section is a critical showcase. May be written late in the process, e.g., after you complete Results and Methods section. Session 2

The first sentence should stimulate the interest of the reader. Example 1: Poor: The purpose of this article is to show that case management can be a cost-effective approach in patient care. (unnecessary words) Improved: Case management can be a cost-effective approach in patient care. Session 2

The first sentence should stimulate the interest of the reader. Example 2: Poor: From the beginning of time, strokes have been a major health problem. (trite, negative) Improved: Advanced treatments for stroke patients are giving them new hope. Session 2

Three Important components in this section. The topic to be covered and why it is important (The rationale) The purpose of the studies. The hypothesis that led to the investigation. Session 2

Try to state: What’s new? What’s special? What’s significant? How to do it? Provide a brief review of the literature and cite findings that led to the present studies. Example: Good: In inner-city adolescents, the increased incidence of illnesses related to sexuality demonstrates a lack of understanding of these problems. Through counseling and referrals, nurse practitioners in our hospital developed a procedure to reach this population and reduce the occurrence of these diseases. Session 2

This section should be short – 500 words or less. How to do it? Discuss any unknowns and controversies that exist , with respect to the rationale for the studies. The information should be fresh/novel, interesting, and specific. Much of the Introduction should be written in the present tense, when you mention the published data/hypothesis. This section is best written in the active voice. The active voice gives writing a sense of strength, energy, and direction. (It is also 20-30% shorter than the passive voice.) Session 2

You need a clearly stated HYPOTHESIS and Approaches. How to do it? State the hypothesis directly. Set up the problem and show how it was dealt with. It is acceptable to briefly state the conclusion. Use only the most important references. Do not refer to individual scientists unless it is necessary to contrast results from different laboratories. (This principle applies also to other sections of the manuscript.) Preliminary reports should be mentioned. If there are related publications that will be published soon, they should be mentioned. (But you need to check the journal format, with respect to unpublished data.) Session 2

Introduction/Background Summary (1)
Include in this section: A brief review of the field (~1 paragraph), including a description of areas in the specific field that are unclear or uncharacterized. An introduction to the present study (~1 paragraph), including hypothesis, major models and readouts, and key conclusions A brief comparison of the present study to the current knowledge, concluding with the significance and possible impact. A simple figure for testing system or agents that are new to the field, e.g., structure for a newly identified chemical that has been published. Session 2

DO NOT include in this section: A lengthy review of the field or related fields Methods used for the paper* *For papers detailing the discovery or design of a new method, this may sometimes be mentioned. Results Discussion Unrelated materials Complex table or figures Session 2

Common problems: Overly state the broad research area Inclusion of textbook information Lengthy citation of old research Descriptions of the results and methods from published studies or the present study Discussion of the results of the present study Inclusion of identical sentences from the Abstract or other sections, especially the discussion section. Inclusion of references that are not generally available, such as non-English publications Too short or too long Overly negative to studies of other groups Over-emphasize previous studies from the same group and or ignore studies from other groups Including complex table or figures Session 2

Materials and Methods (1)
General Suggestions: For beginning authors, this section can be written first because it is easiest to write. The format is usually specific to the journal. Subheadings are characteristically used. Much of this section is written in the past tense, passive voice. Much of this section can be included in the supplementary data section This section can be placed after the Discussion section in many journals. Session 2

This section should be specific, providing sufficient details that allow an experienced researcher in the related field to repeat the experiments in this study. How to do it? Provide sources of key materials and describe preparation of non-standard solutions. Experimental animals, plants, and microorganisms should be identified by genus, species, and strain, as well as age. Sources should be listed and special characteristics described. For human subjects, the criteria for selection should be described, and a statement relating to “informed consent” should be included. Provide sufficient details of the experiments. Descriptions of new methods should include all the needed details. If the methods have been published, references to the specific publications can be used. Do not describe previously published procedures in long detail, but do describe any modifications. Describe the study design and procedures for analysis of the data. Provide information on statistical analyses performed and state the number of observations in each group. Session 2

Include in this section: All the methods used to generate all of the data presented in the results section. Strains and ages of animals, doses used, treatment routes and durations, and other details that would allow the reader to repeat the experiments. Citations for protocols used previously. Detailed descriptions of new techniques/models or changes in standard techniques. Methods used to analyze data. A statement indicating that informed consent was obtained (if you are reporting a clinical study) or that your experiments were in compliance with your institution’s animal regulations. Most used subheadings: Chemicals and reagents; Instruments; Animals; Subjects; in vitro assays (specific); in vivo models and treatment; Analytical methods; Data and statistical analysis Session 2

Do NOT Include in this section: Standard instruments, common buffers, routine clinical chemistry Published synthetic pathway for test compounds Lengthy descriptions of commonly used procedures (Western blotting, RT-PCR)- a brief mention of the antibodies used and the primer sequences and PCR conditions is sufficient. Non-standard abbreviations for reagents or procedures. Results Discussion of the selection of the models and assays Acknowledgments Session 2

Common Problems: Overly detailed descriptions of common protocols. Too few details about new or difficult methods. Insufficient details about models (for example, no age or strain of animals is mentioned). Laboratory jargon and non-standard abbreviations. Too long or too Short. Methods section does not match the results section and/or the figure/table legends. No statistical analysis section. No mention on regulatory approval for animal use or human trials. Written as a laboratory protocol. No vendor information for specific agents/instruments (City, country) Redundancy and Inconsistency Session 2

Results (1) General Guidelines : Session 2
Present results in a logical (not necessarily chronological) order. Give the “big picture”, especially for each set of experiments Present selected data. “A fool collects facts; the wise man selects them.” – John Wesley Powell. To maintain momentum, the evidence must tell a story and support the conclusion. Write in the past tense. Provide sufficient interpretation of data to lead the reader from one concept to the next but leave detailed analysis and comparison of findings for the Discussion section. Key previously published data can be referred but not the actual data Avoid duplication of information in the text and in tables and figure legends. Session 2

Results (2) Include in this section:
The most interesting and clear data obtained from your studies. Illustrations of various types (for example: figures, photographs, and tables). A clear and concise description of your studies and the data. Properly use subheadings to organize the data Session 2

Results (3) Do Not Include in this section:
Discussion material. (The Results should not discuss the implications of the data.) Detailed methods and materials. Don’t include titles on figures. This information should be in the figure legends. Too many figures and tables. (Well written manuscripts contain only a few important, clear figures). Include only enough to tell your story. Too many references. (A few may be cited if necessary, but these should be kept to a minimum.) Session 2

Results (4) Common Problems:
Repetition of data in figures, tables and text. Inclusion of Discussion material. (For example, inclusion of what the results mean and how they are related to previous results.) Lack of sufficient details about the experiments. (Are the data representative of repeated experiments? Why were specific treatment durations or doses chosen?) Lack of statistical analysis and/or indication of significance in figures/tables. Session 2

Results (5) Common Problems:
When the Methods section is placed after the Discussion section, the lack of experimental details in the Results section may result in difficulties in presenting and understanding the results. Session 2

Illustrations (1) General Suggestions for Illustrations : Check the journal to see how illustrations are presented. The text is easier to write after illustrations have been prepared. A goal is to simplify the message without falsifying the data. Session 2

Illustrations (2) General Suggestions for Tables: Tables present exact values and allow comparisons between data points. Tables should be understood without referring to the text. In general, use only one table per 1000 words of text. The text must refer to the table by number. Numbers should show no more decimal places that are essential for reasonable precision and accuracy. Captions should be concise, contain key words, and be parallel for all tables in the manuscript. Captions should not be sentences. Do not include columns containing only one repeated value. Tables should contain no vertical lines. Use “straddle lines” over all columns of items to which the heading refers. Comparisons between like elements are made down columns, not across rows. Align decimals in columns. Session 2

Illustrations (3) Examples for Tables: Poor: Table 1 shows that animals dosed with 4-HPR developed fewer adenocarcinomas. Better: Animals dosed with 4-HPR developed fewer adenocarcinomas (Table 1). See the booklet for an example of a table with a title, column headings, row headings, straddle line, field, and footnotes. Session 2

Illustrations (4) General Suggestions for Graphs: Session 2
If you choose to use a graph, it should convey information better than a text or a table. Graphs should be understood without referring to the text. Graphs show trends, overall patterns, and interactions between variables. Graphs demonstrate change over time or concentration. Graphs do not emphasize individual values. Graphs should avoid wasted space. Place the independent variable on the x-axis and the dependent variable on the y-axis. On both axes, plot the length of intervals so that the curves are not excessively flat or steep. Captions should be concise, contain key words, and be parallel for all graphs in the manuscript. Captions should not be sentences. The number of curves on a graph should be limited to five. It is generally better to use symbols (●, ■, ▲) than line patterns. The curves should be bold and easy to see; the axes and tic marks can be smaller/less bold , but should still be easy to see. Session 2

Illustrations (5) Fig. 6 Plasma concentrations of adaphostin following intravenous administration to each of two dogs at a dose of 7.5 mg/kg. Session 2

Illustrations (6) General Suggestions for Other Illustrations : Bar charts, which have only one measurable axis, dramatize differences, but they are not numerically specific. MCF-7 MDA-MB-468 Session 2

Illustrations (7) MDM2-p53 Interaction
General Suggestions for Other Illustrations : Diagrams illustrate complex relationships, pathways, and interactions Ub Ub Ub Ub Ub Ub Favors Nuclear Export p53 MDM2 MDM2 Ubiquitination p53 Inhibits Transactivation Activity p53 p53 Target Genes Tumor Suppressive Activity MDM2-p53 Interaction Session 2

The leaves of Panax notoginseng
Illustrations (8) General Suggestions for Other Illustrations : Flow charts show sequential processes and describe causation Combined the extracts Extracted with 70% EtOH Evaporated in vacuum Purified with D101 resin Hydrolyzed with HCl Extracted by EtOAc Silica gel chromatography Eluted with petroleum-EtOAc Reversed-phase CC Eluted with 80% MeOH 20(S)-25-OCH3-PPD EtOH extracts Resin column 70% EtOH eluate Fraction 3 EtOAc extract The leaves of Panax notoginseng Session 2

Illustrations (9) General Suggestions for Other Illustrations :
Pie charts show proportions, parts of a whole, or percentages. MCF7 Cells 20(S)-PPD 20(S)-25-OCH3-PPD MDA-MB-468 Cells 20(S)-PPD 20(S)-25-OCH3-PPD

Illustrations Summary (1)
Include in this section: Clear labels for all parts of the figure, table, or illustration. Consistent font styles and sizes (if possible) for each figure. Labels indicating statistical significance (where applicable). Legends describing the method used to obtain the data and what special symbols indicate. Session 2

Do Not Include in this section: Too many parts per figure. (Four to six parts per figure is acceptable; more than that leads to confusion.) Small fonts. (Ideally, the font should be at least 10 pt.) Large tables. (More than 5 columns or longer than 2 type-written pages in length is too large.) Figures of poor quality. (Most journals now have minimum resolution requirements for photographs, figures and illustrations.) Session 2

Common Problems: Unclear figures (low quality). Differences in font size and style between figures. Unclear figure labels. Misspelled labels. Missing units (hours? minutes? days?). Overly complex table or figures. Redundancy and inconsistency Session 2

Discussion (1) General Suggestions:
The primary function is to relate the present work to previous reports and to point to future efforts. An introductory statement can describe – again – the purpose of the studies. If it is reasonable, the topics in the Discussion should be parallel to those in the Results. Main purpose is to present principles, relationships, and generalizations about the findings reported in the paper. The length of the Discussion is generally proportional to the amount of new information presented (1/4 text). It should contain about one word for every four words in other parts of the manuscript. Session 2

Use present and past tense, as appropriate. Present tense: Other published work, including your own work. Past tense: your present work Avoid re-stating the Background/Introduction information but prepare the Discussion in the context of the Background/Introduction. Avoid reiteration of Results, but discuss interpretations and conclusions based on the results. Show how your data agree with previous results; point out exceptions. The conclusion should restate the thesis. Session 2

Do not recapitulate results. Discuss theoretical and practical applications. State the significance of the results and how the results advance knowledge. Limited speculation is acceptable. Identify future studies that are needed. Avoid undue claims of primacy (being first?). Present a strong ending. Session 2

Clearly and briefly state the conclusions and the significance. Conclusions should be logically derived from data presented. Compare how the conclusions agree or contrast with previously published work. Don’t try to hide unclear thinking with excess words. Identify possible sources or error and inadequacies in the work. Present a strong ending. Session 2

Discussion Summary (1) Include in this section:
Principles, relationships, and generalizations about the data. A description of how your data agree with previous results, and any exceptions. Conclusions logically derived from the data. A comparison of how the conclusions agree or contrast with previously published work. Most used structure (usually no subheading): purpose and significance of the study; summary of key findings; interpretation of the main results and comparison with previous works (do not have to be the same order as Results; possible mechanisms; limitation of the present study; future studies; summary or conclusions; implication and translational potential. Additional illustrations can be used to facilitate discussion; but not new data. Session 2

Discussion Summary (2) Do Not Include in this section:
Textbook information Repetition of the Introduction, Methods/Materials or Results sections Extreme words, for example, “ extremely” “first” “very,” “super,” and “crucial” Concepts that were not introduced earlier in the manuscript Similar discussion from similar published papers Session 2

Discussion Summary (3) Common Problems: Textbook information
Repetition of the Introduction, Methods/Materials or Results sections Extreme words, for example, “ extremely” “first” “very,” “super,” and “crucial” Concepts that were not introduced earlier in the manuscript Similar discussion from similar published papers Inconsistency with other sections Recite Illustrations Length: too short or too long Overemphasis of the importance of the findings or previous work from your own group Too much speculation Misinterpret other published studies Overly use subheadings Session 2

Session 2 Writing Tips for the Abstract, Title, References, and Acknowledgements (ATRA) sections Dr. Zhang has presented general concerns in manuscript preparation, including the sections Introduction, Materials and Methods, Results, and Discussion. Today . . .

Abstract (1) General Suggestions:
It is a “window” that reveals the contents of the manuscript. Except for structured abstracts (more common nowadays), it is a single paragraph. Limited length: <250 words It should summarize each of the main sections of the paper, including the following: the background (1-3 sentences) the hypothesis (1 sentence) model systems used general methods a short description of the results a statement regarding the significance of the work Most readers will read the abstract and not the entire manuscript. The “window” shows what is inside. The structured abstract includes Objectives (includes hypothesis), (Design), Methods, Results, and Conclusions (implications). For review articles: Purpose, Methods (how studies were selected), Results, Conclusions. The limited length requires concise statements. Session 2

It should be complete and intelligible without reference to the text. Generally, it should be written in the past tense, especially methods and results . Within the space allowed, all key findings should be included. It should ordinarily be written after a semi-final draft of the manuscript has been prepared. In contrast to a meeting abstract, the abstract for a manuscript should ordinarily not include actual data values. From the abstract, one should be able to determine what was done. Since numbers are not generally included, one may not be able to assess completely the impact of the work. Although it is customary to use the past tense, the present tense gives a “fresh” and “stronger” view of the information. We will see an example of this. If you use the present tense, you may overstate the results; if you use the past tense, you may understate the results. Remember to review the abstract after the final draft of the manuscript has been prepared. The abstract should reflect accurately reflect the information in the body of the text. Session 2

In general, citations should not be included. In general, abbreviations are not included, unless the same, long term is used repeatedly. (Abbreviate at the first use in the text) Terms included in the abstract will be included in various databases for literature searches. Importance of the Abstract: Its contents can establish the interest of the editor and reviewers and will determine if the reader actually reads the manuscript. Editors will often use the abstract to determine whether the paper should be reviewed for their journal. After the paper is published, readers may read only the abstract. A citation could be included if your data are confirming or in conflict with a previous report. Make your data available to interested readers. Remember the purpose of the Abstract. You are a salesman; sell what you have done. Session 2

Abstract (4) Include in this section: Background for the study
The purpose of the study Sufficient details to allow the reader to understand what the manuscript is about and what the major points are (Experimental details would include, for example, the number of test subjects and controls, species of animals, drug dosages and routes of administration, and tumor yields.) Major findings (new and important) Principal conclusions Any items/sections required by the target journal This is in review. In some cases, the editor will insert the reference at the end of the abstract. Session 2

Abstract (5) Do Not Include in this section: Unnecessary abbreviations
Detailed results (including numerical values for data) Statistical values (p-values) for the findings Overstatement of the significance Extreme words Vague statements, such as, “The significance of the results is discussed” or “Future studies are needed.” It is acceptable to include statistical values in epidemiological studies or if a main point of the paper is to show that something is statistically significant. Instead of stating, “These data can lead to a cure of gliomas,” it would be better to state, “This information could be useful in the development of new treatments for gliomas.” Extreme words: critical, crucial, tremendous, outstanding, monumental. Session 2

Abstract (6) Common Problems: Not exciting Too long or too short
Too much background information Not enough information about the results Unnecessary citations Excessive numerical data Inconsistency with other parts of the text Too much discussion or speculation Unimportant subject or minor contribution. The editor may reject the manuscript if the abstract is too long (over the specified limit). There is no need to write a review in the abstract. “Expression of the protein changed after the cells were exposed to NO.” “The transformed cells had a different phenotype.” Numbers can clutter an abstract. For example, there is no need to present, in the abstract, all of the data present in a large table. A final step in manuscript preparation is to make sure that the abstract reflects the data and interpretations in the text. Problems can easily develop when several people are involved in preparing the manuscript. Session 2

Abstract (7) Example: Session 2
Down-regulation of p53 by MDM2-mediated proteasomal degradation makes cells resistant to apoptosis. The MDM2-p53 interaction is well characterized, but the mechanisms that regulate the interaction are not well understood. Here, we show that PA28γ, a proteasome activator that inhibits apoptosis and promotes cell cycle progression through unknown mechanisms, exerts an effect as a cofactor in the MDM2-p53 interaction. The polymer form of PA28γ interacts with both MDM2 and p53 proteins and facilitates their physical interaction. This promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. Elimination of endogenous PA28γ in human cancer cells abrogates MDM2-mediated p53 degradation, increases the activity of p53, and enhances apoptosis. These findings reveal the mechanism by which PA28γ affects apoptosis and proliferation. Manipulation of the level of PA28γ, an approach that would regulate the cellular content of p53, may improve the efficacy of current cancer therapies. Discuss the different sections. Note that it is written in the present tense. In line 4 from the bottom, “the mechanism” may be an overstatement. Session 2

Remember: Abstract (8) The abstract should contain the following:
Background Purpose Major findings Conclusions Try not to overstate or understate and try to make the information clear and precise. Session 2

Title (1) General Suggestions:
Usually written in “Title Case,” with upper-case letters for nouns and other words of more than four letters. As far as possible, use specific terms, for the title is a key element of the manuscript. Key words should appear in the title. Use the fewest words possible to adequately describe the contents of the paper. Explain “Title Case.” “Transgenic mice” is more specific than “rodents” or “mice.” “PC3 cells” is more specific than “cancer cells.” Identifying the subject of your paper can help you identify “key words.” We used transgenic mice to show that cancers quickly develop in the prostate. Session 2

Title (2) General Suggestions: The first noun should be powerful.
Sentence titles, which are now often used, can appear to be dogmatic. It is generally appropriate to choose the title when the manuscript is almost complete. Many people will read the title, including abstracting services. Series titles and titles with colons (“hanging titles”) are generally not desirable. Titles should almost never contain abbreviations, chemical formulas, proprietary names, or jargon. “The oncogene”; “Pharmacokinetics”; “Epidemiology”; “Clinical evaluation” in contrast to: “A study on”; Investigations of”; “Examination of” Dogmatic: Sentence titles tend to overstate. “This is the way it is; there can be no other way.” Manuscripts can develop as they are written. You may develop a new interpretation or realize a new limitation. 1000 people read the title; 10 read the abstract; 1 reads the entire manuscript. Example: Conformationally defined retinoic acid analogs: 4. Potential new agents for acute promyelocytic and juvenile myelomonocytic leukemias. Last year, we had a question about abbreviations in titles. The next slide reflects my changing view on this. Session 2

Title (3) Comparisons: Which of the following is preferable?
Involvement of GREB1 (gene regulated by estrogen in breast cancer 1) in breast carcinogenesis Involvement of gene regulated by estrogen in breast cancer 1 (GREB1) in breast carcinogenesis Involvement of gene regulated by estrogen in breast cancer 1 in breast carcinogenesis Involvement of GREB1 in breast carcinogenesis We can vote on this. Session 2

Title (4) Comparisons: Poor: “Action of Streptomycin on Mycobacterium tuberculosis” Better: “Inhibition of Mycobacterium tuberculosis growth by Streptomycin” Poor: “Mechanism of Suppression of Non-transmissible Pneumonia in Mice Induced by Newcastle Disease Virus” Better: “Mechanism of Suppression of Non-transmissible Pneumonia Induced in Mice by Newcastle Disease Virus” “Action” is not a strong word. It is vague. Mice are not “induced.” Note the Title Case. All nouns and other words with more than 4 letters. Session 2

Title (5) Include in the title:
A clear, specific, and concise statement reflecting the major findings reported in the manuscript. Key words that will attract the interest of the editor, the reviewer, and reader. This is a test of your clarity, accuracy, and precision in writing. Use strong words that will attract attention. Session 2

Title (6) Do Not Include in this section:
Roman or Arabic numerals showing that the paper is part of a series Jargon Abbreviations other than well-accepted standards such as, DNA, RNA, and RT-PCR Punctuation other than commas (and commas should be used sparingly) The words “study,” “critical,” “very,” or “first” Extensive prepositional phrases (of…in…of…) Conformationally defined retinoic acid analogs: 4. Potential new agents for acute promyelocytic and juvenile myelomonocytic leukemias. Jargon: carried out, dose preps, lab. Check with the journal to determine what abbreviations are accepted. A list (or a link to a list) is often provided. Session 2

Title (7) Example: Poor: The use of microbiological and enzymatic assays in studies on the disposition of 2'-deoxycoformycin in the mouse. Better: The disposition of 2’-deoxycoformycin in mice as determined by microbiological and enzymatic assays. I wrote this 30 years ago. It is not good. Session 2

Title (8) Common Problems: Not exciting Too long or too short
Not enough information about the finding Inconsistent with other parts of the text Extreme words Speculation A study performed with old techniques. A minor advance. “Changes in MDM2 in the presence of genistein – too short and imprecise. Too long: reader can lose interest or be confused. Too short: not enough information to attract the interest of the reader. (We will see examples of this.) After all authors have made their contributions, you may need to change the title. If the text changes, the title may need to be changed. Extreme words: critical, crucial, tremendous, outstanding, monumental. Speculation: could be, might be, perhaps Session 2

Title (9) Examples: Controlling the Bollworm
Investigations into the Effects of Several Selected Phenolic Acid Compounds on the Mortality Rate, Developmental Time, and Pupal Weight Gain of the Cotton (Gossipium hirsutum L.) Bollworm (Helicoverpa zea Boddie) in Studies Involving Larvae Fed a Synthetic Diet in the Laboratory The Effects of Selected Phenolic Compounds on the Mortality, Developmental Time, and Pupal Weight of Helicoverpa zea Boddie: Synthetic Diet Studies Benzoic and Cinnamic Acids in Synthetic Diets Retard Development of Helicoverpa zea Larvae Influence of Benzoic and Cinnamic Acids on Mortality and Growth of Bollworm Larvae Toxicity of Benzoic and Cinnamic Acids to Helicoverpa zea Larvae Too short, too long, too many details, too restrictive, vague, good. Session 2

Title (10) Example: Original: Genistein Down-Regulates MDM2 Expression Independent of p53, a Previously Unrecognized Mechanism of Action Final: Genistein, a Dietary Isoflavone, Down-Regulates the MDM2 Oncogene at Both Transcriptional and Post-Translational Levels Not bad, but most new data are “previously unrecognized.” Session 2

Title (11) Exercise: Improve the following title:
Poor: Assay for TCGF Activity in Leghorn Chickens in the US Better: An Analytical Method for T-Cell Growth Factor Activity in Leghorn Chickens Eliminate abbreviation. Not important that the chickens are in the US. “Assay” is obsolete. Session 2

Remember: Title (12) The title should contain the following: Key words
Few words Session 2

Running Title A shortened, but descriptive version of the title (usually limited to about 60 characters and spaces) Placed on the title page Often appears on each page (or every other page) of the manuscript. This represents the shortest description of the work. Session 2

Key words Most journals now ask for 3-6 key words to make it easier to link your article to search engines. These words should indicate the major focus of the manuscript (e.g., genistein, MDM2, and cancer). Suitable terms can be found in the Medical Subjects (MeSH) list of Index Medicus. See Generally, these words should be in the title. Session 2

List of Authors Example of authors:
Mao Li,1 Zhuo Zhang,1 Donald L. Hill,1,2 Xinbin Chen,2,3 Hui Wang,1,2 and Ruiwen Zhang1,2* 1Department of Pharmacology and Toxicology, Division of Clinical Pharmacology; 2Comprehensive Cancer Center, 3Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL * Corresponding author. Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Blvd., Volker Hall 113, Birmingham, AL 35294, USA. Tel.: ; Fax: ; Check a recent issue of the journal to which the manuscript is being submitted. Session 2

References (1) General Suggestions – Part A:
Limit the number of citations to a number consistent with articles published by the journal. For most publications (except reviews), fewer than 50 citations are adequate. For references, include primary sources if possible. Cite reviews rather than each article covered by the review. Instead of listing numerous references for a prior discovery, it is acceptable to state, “as summarized by . . .” or “as reviewed by . . .” Avoid excessive self-citation. Include citations of pertinent manuscripts published by others. (Remember who your reviewers might be!) A long list of references can take up expensive space. Again, refer to a recent issue of the journal to which the manuscript is being submitted. It is generally wise to mention the person who discovered protein, gene, or phenomenon. As an alternative, you can refer to an appropriate review. Citing your own work too many times gives a poor impression. Session 2

References (2) General Suggestions – Part B:
Check references for accuracy. Do not put references to unpublished data in the References. Include them in the text. Example: (R. Zhang and D. L. Hill, unpublished data) Check abbreviations: Is it Journal of the American Chemical Society, Jour. Am. Chem. Soc., J. Am. Chem. Soc., J.A.C.S., or JACS? Standard abbreviations for journals can be found at It is distracting for a reviewer to find that his work is improperly referenced. If references are numbered, make sure each number in the text matches the appropriate number in the list of references. Session 2

References (3) General Suggestions - Part C:
Do not cite more than three references per statement. For a topic with a large number of possible references, site the original reference (the one reporting the initial discovery) and the most recent reference on the topic, or site two comprehensive reviews. Make use of available software to simplify formatting and putting your references in order (for example, EndNote). Sample references can be found at Don’t use something like (1-23). Session 2

References (4) Format: Follow the format for your selected journal. This style is used by some journals: Halpern SD, Ubel PA, Caplan AL. Solid-organ transplantation in HIV-infected patients. N Engl J Med Jul 25;347(4):284-7. Note: If the journal carries continuous pagination throughout a volume (most do), the month, day, and issue number can be omitted, as follows: Halpern SD, Ubel PA, Caplan AL. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7. Session 2

References (5) Remember: Limited number Primary sources
Check, check, check Session 2

Acknowledgements (1) General Suggestions:
Contributions that do not justify authorship (For all of these, permission must be obtained.): Technical help Financial and material support Special facilities or instrumentation that are supported by another funding source Contributors of materials (for example: vectors, cells, animals) Financial relationships that may pose a conflict of interest Undergraduate lab assistants. Financial support from the department and/or government sources. Core facilities. Dr. D. Chen owns 5% of the stock issued by Neutrichemicals, Inc., which sells genistein. Session 2

Acknowledgements (2) Example:
Grant Support: NIH/National Cancer Institute grants R01CA and R01 CA---- (R. Zhang), Department of Defense Prostate Cancer Research Program grant number W81XWH (Z. Zhang), National Cancer Institute/University of Alabama at Birmingham Comprehensive Cancer Center Junior Faculty Development grant (H. Wang), and Comprehensive Cancer Center or Cancer Pharmacology Laboratory (H. Wang). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. We thank Dr. J. H. for excellent technical assistance and E. R .for assistance in editing and preparation of this article. The second paragraph is inserted by the editor. Session 2

Finishing (Editing) a Manuscript (1)
General Suggestions: Eliminate all unnecessary words. Choose precise words. (Precision in writing relates to the degree to which words convey what is meant to be said.) Do not use the same word repeatedly. Use a thesaurus to find fresh words. Do not begin all sentences with the same word. Read the manuscript aloud. Proofreading: This can be done sentence by sentence, backwards, so that there is concern only for mechanical and grammatical errors – none for content. Make all appropriate changes. This is work. Unnecessary words: The most common problem with scientific writing. High school training. RZ has talked about precision. Find out how to use an English thesaurus. Session 2

General Suggestions: Wait for a day and then read it aloud again. When you can read it aloud, from start to finish, without making any changes, it is nearing completion. Use only limited appropriate references to your prior work. Use all pertinent references, even if prior reports do not agree with your findings. Have someone else read the manuscript and make comments, but don’t be discouraged or taken off track. Session 2

General Suggestions: Perform a “spell check” and “grammar check.” Perform “accept all changes.” Complete the mandatory submission form and secure all necessary signatures. Contact the editor if you have any questions. Session 2

Cover Letter (1) General Suggestions:
This is best accomplished after the manuscript is written, however, the editor can be contacted before the manuscript is submitted if the authors want to determine whether the study will be of interest to the journal. Prepare a business letter on quality letterhead paper. Styles are block, modified block, and indented. Center the text on the page. Session 2

Cover Letter (2) Include in the letter:
The title of the article, the nature of the work, and the major points (but not the complete abstract). The type of article that the manuscript represents (e.g., short communication, review). A statement regarding possible redundant publications. A statement regarding conflicts of interest. A statement that the manuscript has been approved by all authors. Your telephone number and address. Session 2

Cover Letter (3) General Suggestions:
It is acceptable to ask that a particular individual be excluded from reviewing the manuscript. Follow the pre-submission checklist, if one is provided. Sign in black or blue ink. Send to the appropriate editor, as indicated in “Instructions for Authors.” You should receive a communication “Acknowledgement of receipt.” If there is no response, inquire after 4-6 weeks. Session 2

Submission (1) General Suggestions:
Resolve any authorship issues, for the submission form is a legal contract. Each author signing the document assumes responsibility for the originality and integrity of the information contained in the manuscript. Resolve issues related to prior publication. Follow the “Instructions for Authors” regarding the organization of the manuscript, presentation of illustrations and tables, and format/style for references. Observe word and/or page limitations for the entire article and for the title, running title, and abstract. Session 2

Submission (2) General Suggestions: Use a title page for the title of the manuscript and for a list of the authors. Use accepted, standard abbreviations or include a list of special abbreviations with their spelled-out forms or definitions. Insert page numbers. Provide all authors an opportunity to comment on the manuscript, but set a deadline for a response. Example: “I plan to submit the manuscript in two weeks. If I do not hear from you in that time, I will assume that you have no concerns.” Session 2

Submission (3) General Suggestions:
Complete the “Quality control checklist for manuscript submission” Ensure that all requested items are submitted to the journal office. This includes the manuscript submission fee (up to $100) and any required submission and conflict of interest forms. Retain a final copy for your files. Submit the manuscript online or send the manuscript by first-class mail. Session 2

Quality control checklist for manuscript submission
Every number included in the text, figures and tables has been verified Figure/illustration/table legends and labels have been checked for accuracy The List of Authors is correct (and all names are spelled correctly) The author institutions/addresses are correct and up-to-date The methods and conditions described (especially doses used) have been verified The abstract is interesting and accurate The manuscript follows all of the journal’s requirements (length, font size, style, number of figures, number of references, resolution of illustrations, etc.) The document and figures/tables/illustrations and their legends are free of typos and misspellings All authors have seen the final draft and agree to its submission All other materials (cover letter, submission fees, copyright agreements) have been signed and are ready for submission Session 2

Summary Nothing is small, with respect to preparation and submission of a manuscript. Do your best, real best. Hope for the best; prepare for the worst. Be prepared for revision. (Almost every manuscript needs to be revised before it is published.) Session 2

Session 2 Summary Simple writing style Reading, Reading, Reading
Thinking, Thinking, Thinking Writing, Revising, Revising Weigh your words as precisely as you weigh your chemicals Key to Success: Seeking Advice

发表英文医学论文技巧 Session 3 Communication with Editors

Understanding the “RE’s”
Search and Research Write and Rewrite/Revise View and Review Session 3

Duties of Editors Hot Topic: Who are the editors? Session 3
Screen manuscripts for merit, evaluating them for the following: Suitability for the journal The presence of fatal flaws Redundancy Impact/importance of the topic Select reviewers based on their qualifications, honesty, and objectivity, including those suggested by the authors. Eliminate bias (positive and negative) to the extent possible Assign potentially acceptable manuscripts on to one or more qualified referees for review. Correspond and work with authors. Make the final decision in regard to submitted manuscripts and provide the author with a rationale for the decision. Maintain anonymity of reviewers. Maintain the confidentiality of unpublished material. Perform appropriate editing. Handle cases of alleged misconduct at the lowest possible organizational level. Involve institutions at which the research was accomplished if, after an initial inquiry, the allegations appear to have merit. Hot Topic: Who are the editors? Session 3

Communication with Editors (1)
Inquiries If you don’t hear from the editor within a month, contact him/her. Use a pleasant sentence such as, “I wonder if any conclusion has been reached about my manuscript, “Genistein inhibits expression of the MDM2 oncogene,” which I submitted on January 24, 2005.” Editor’s Options (not only first submission) Accept without revisions (a rare occurrence). Accept with revisions (a common occurrence). Acceptable pending revisions (usually minor revisions) Unacceptable at current form: major revision; minor revision Reject/Do not accept (more common since authors prefer to submit to high-impact journals.) Hot Topic: How many times can you revise your manuscript? Session 3

Manuscript Accepted: The acceptance letter (or ) will usually state when you can expect to receive the proofs. A form related to copyrighting for the manuscript will be sent to you. The main editor (or copy editor) will make stylistic changes, according to the journal’s guidelines. A copy (galley proofs), set in type as it will appear in the journal, will be sent to you. Often, queries ask if suggested editorial changes are acceptable to you. Read the proofs line-by-line and note any necessary changes by use of proofreader’s marks. Do not dispute the recommended changes, unless the continuity or integrity of the manuscript is affected. Publication may require several months. Hot Topic: How can you choose the form of publication? Session 3

Acceptable Pending Revision Do not be upset by the reviewers’ and editor’s comments. Try to understand clearly what the reviewers are saying. Look for clues in the editor’s cover letter. If the reviewers did not understand something, it may not have been clearly explained. Consider which issues are important, and concede minor points. Acknowledge where you have made mistakes and correct them. If more than one referee points out the same problem, it is probably real. Discuss the issues with a trusted colleague. Do not dispute the recommended changes, unless the continuity or integrity of the manuscript is affected. It is best to revise the manuscript in accordance with the reviewers’ comments, perform any suggested experiments, add any appropriate additional material, and re-submit it. Respond quickly and in detail. Hot Topic: At this time, can my paper be rejected? Session 3

Acceptable Pending Revision: Response to Editors/Reviewers Point out the positive comments made by the reviewers. Make a numbered list of the points in the critique and prepare a thoughtful and clear response for each. For each point, describe what changes you have made in the manuscript and indicate what portions of the text have been deleted, added, or altered. Stand firm if that is the proper thing to do. If you think that the reviewer is wrong, respond politely and diplomatically, giving detailed reasons and appropriate citations. Omit emotional responses. Never tell the editor that he/she is wrong. Thank the editor and the reviewers for their help in improving the manuscript. Have a neutral colleague review the response before sending the manuscript back to the editor. As before, provide all authors an opportunity to comment on the manuscript, but set a deadline for their response. Hot Topic: What should I do if I really don’t like the reviewer or editor? Session 3

Sample letters Accepted pending revision Accepted Rejection Hot Topic: Which one is more important, response letter, revised paper, or both? Session 3

Accepted with Modifications
From: Sent: Thursday, May 05, :21 AM To: Ruiwen Zhang, M.D. Subject: Cancer Research: Decision Rendered on Manuscript CAN Version 1 Dr. Ruiwen Zhang University of Alabama Depts Of Pharmacology & Toxicology UAB, VH 113, Box 600 Birmingham, AL United States RE: CAN Version 1 Genistein, a dietary isoflavone, down-regulates MDM2 oncogene at both transcriptional and post-translational levels Dear Dr. Zhang: We regret to inform you that your above-referenced revised manuscript is not acceptable in its present form for publication in Cancer Research. The comments of our reviewers are enclosed for your information. The Editors will consider a manuscript that has been revised in response to the criticisms. Any resubmitted paper should be written as concisely as possible. If you resubmit, please see the instructions appended below for information on preparing and resubmitting your revised manuscript. Please note that if you plan to resubmit the manuscript, you must do so within three months. If you resubmit this manuscript after this deadline, the manuscript will be treated as a new submission, assigned a new manuscript number and subject to an additional $75.00 submission fee. We appreciate having had the opportunity to review your work. Sincerely, Charis Eng, MD, PhD Senior Editor Session 3

Response to Accepted with Modifications
December 12th, 2006 Charis Eng, M.D., Ph.D. Senior Editor, Cancer Research Re: Manuscript CAN Curcumin, a Dietary Component, Has Anti-Cancer, Chemosensitization and Radiosensitization Effects by Down-Regulating the MDM2 Oncogene Through the PI3 Kinase/mTOR/ETS2 Pathway Dear Dr. Eng: Thank you for your dated September 12th 2006, regarding the review of our manuscript. We appreciate the comments and suggestions from you and the reviewers regarding the assessment of the study and have found them helpful in preparation of the revised manuscript. We are glad to learn that you are willing to give further consideration to a suitably revised version that addresses the criticisms raised by the reviewers. As suggested by the reviewers, in addition to modification of the text, additional experiments have now been performed to characterize the role of the PI3K/mTOR/ETS2 pathway in the modulating the effects of curcumin on MDM2 expression. Specifically, we employed real-time PCR to confirm the downregulation effects of curcumin on the MDM2 mRNA level (Fig. 2A2). Further, to demonstrate the role of ETS2 in the MDM2 expression, ETS2 was knocked down by double-stranded siRNA in PC3 cells. As a result, curcumin (Fig 2D5), the PI3K inhibitor LY (Fig 3B6) and the mTOR inhibitor rapamycin (Fig 3D3) lost the capacity to downregulate MDM2. To exclude the possible involvement of Akt, WT (wildtype)-, CA (constitutively active)- and DN (dominant-negative)-Akt were overexpressed in PC3 cells. With these alterations, we did not note appreciable changes in MDM2 expression either in the presence or absence of curcumin (Fig 3C). Moreover, a more specific PI3K inhibitor, LY294002, which was suggested by a reviewer, was included in the study to evaluate the role of PI3K in MDM2 expression. As expected, we observed a pattern of MDM2 expression changes similar to that when wortmannin was used (Fig 3B4 and 3B5). Finally, we found that the inhibition of mTOR by rapamycin abrogated the effects of the PI3K inhibitor LY induced MDM2 downregulation, suggesting that mTOR is the downstream target of PI3K in modulating MDM2 expression (Fig 3D2). (detailed responses) We trust that the above responses meet the expectations of the reviewers. Their comments and suggestions were helpful in improving the quality of our manuscript and will be applicable in our future studies. Thank you for your consideration. We look forward to hearing from you and to publication of this manuscript. Sincerely, Ruiwen Zhang, M.D., Ph.D., D.A.B.T. Professor, Pharmacology and Toxicology Director, Cancer Pharmacology Laboratory Session 3

Hot Topic: Does the response make a difference?
Communication with Editors (6) Example: Reviewer Comments and Responses Criticism: “The results section is not well organized and not well presented. Figure legends are confusing and incomplete. The organization is hard to follow. There is an abundance of data that are presented in a convoluted manner that doesn’t address the hypothesis.” Poor response: “If the referee would have spent more time reading the paper than pontificating, he/she would have clearly appreciated the logic of the presentation.” Better response: “The results section has been rewritten and re-organized to address these concerns. The data are now presented in a fashion that makes clear the relationships between the experiments and the hypothesis.” Hot Topic: Does the response make a difference? Session 3

Hot Topic: What to do with the rejection?
Communication with Editors (7) Basis for Rejections The article is not suitable for the journal. Little or nothing is new, significant, or relevant. The data may be only confirmatory. Examples: “The science is sound, but no new information is presented.” “This is simply a technical report.” “There is only an incremental increase in knowledge.” Most manuscripts are rejected on the basis of priority rather than the presence of scientific flaws. The article would have limited appeal to the readers of the journal. A similar article has been published. The studies are poorly designed, conducted, or reported. Examples: “The experiments lack appropriate controls.” “The study is largely descriptive.“ Or “The data are only preliminary.” “The article is poorly written and prepared.” Hot Topic: What to do with the rejection? Session 3

Letter of Rejections Dr. XXXX University of xxx
RE: CAN Version 1 Experimental Therapy of Dear Dr : We regret to inform you that your above-referenced manuscript is not acceptable for publication in Cancer Research. Decisions rendered on Cancer Research submissions are based on the Editor-in-Chief’s or Senior Editor's overall assessment of all of the information obtained on a manuscript during the review process. In addition to the reviewers’ comments, such factors as the Associate Editor’s recommendation and the priority scores assigned the work are taken into consideration. Only those manuscripts that meet stringent requirements of high scientific quality and significance, originality, and priority can be accepted. Unfortunately, in light of all of the information at the Editor’s disposal on this manuscript, he feels that your submission does not meet all of these criteria and, therefore, cannot be accepted. We regret that we could not render a more favorable decision on your manuscript, but we appreciate the opportunity to review your work, and we would welcome future submissions from you for our consideration. Sincerely yours, -----, Ph.D. Senior Editor

Hot Topic: How does the rebuttal letter work?
Communication with Editors (8) Responding to Rejections If the rejection is total, you may want to forget about publishing the manuscript (at least in its present form, or in that journal). If you are convinced that the manuscript is worthy of publication, revise it in accordance with the reviewers’ comments, perform any suggested experiments, add any appropriate additional material, and submit it to another journal. (It may have been submitted to an inappropriate journal.) If the reviewers did not understand something, it may not have been clearly explained. If the reviewers indicate that the article is poorly written and/or prepared, that is, if there were defects in the manuscript but not in the data, secure the help of an experienced writer. Hot Topic: How does the rebuttal letter work? Session 3

Functioning as a Peer Reviewer/Editor Determine if the manuscript is appropriate for the journal. If not, it cannot be acceptable regardless of its scientific merit. Evaluate the importance and originality of the research. If the results do not make a substantial contribution to scientific knowledge, other issues are irrelevant. Determine if a clear and testable hypothesis presented. Evaluate strengths and weaknesses of the following: methodology, experimental results, statistical approach, and interpretation of results. Evaluate any ethical concerns. Determine if the results are properly presented and if the conclusions are reasonable. Evaluate the writing style and the presentation of tables and figures. Avoid offensive language. Avoid bias. Provide fair and collegial evaluation. Notify editor of any conflict of interest. Avoid misuse of privileged information. Be prompt. Hot Topic: Why should I be a peer reviewer/editor? Session 3

Session 3 Summary Once again,
Nothing is small when you communicate with Reviewers and Editors Thinking more, Writing less Revising before submission Weigh your words as precisely as you weigh your chemicals Key to Success: Seeking Advice

Take-home Message You can do it, We can help!

Making An English Biomedical Paper: Why, What, and How

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