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    How to write a manuscript

    Get your paper accepted

    Edanz free manuscript writing educational materialsEdanz Group LtdOctober 2010

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    Presentation

    Introduction

    Section One: Preparations before writing

    Section Two: Manuscript structure

    Section Three: Tips for getting accepted

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    To share your research findings and opinionswith the international research community

    Publication success is linked to funding successand career advancement

    Many PhD programs require candidates toachieve a set number of peer-reviewedpublications

    Edanz Group Ltd. | 3

    Why publish?

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    FundingBodies

    Scientists /Clinicians

    GrantWriting

    Journal

    Publication

    Regularly publishing research findings ensures ongoing grantsupport for new research

    Publish or perish

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    How to identify hot topics

    Study design

    What do journal editors want?

    Choosing an appropriate journal

    Ethical issues

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    Section One Preparations before writing

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    Look for clues unexplained findings,controversies

    Read the literature,including relatedfields

    Attendinternationalmeetings

    Greater interest = Greater competition

    Identify your advantages and use them

    How to identify hot topics

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    Have an hypothesis or research questionUse appropriate methods and controlsEnsure sample sizes are large enough

    Use appropriate statistical testsRemove investigator/researcher/patient bias

    Comply with ethical requirements

    Study design Get it right first time

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    Good quality scienceRobust to peer review

    Well designed and executed original research

    Findings of interest to the journals readership

    Work in an active research area (=citations!)

    Work that advances the field in some wayCompliance with ethical regulations

    Clear, concise writing

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    What do journal editors want?

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    Can be the difference between success and rejectionWhat is the main focus of your research and who willbe interested in it?

    What are its strengths and weaknesses?How significant are your findings?

    Are your findings preliminary or are they sufficient to

    make a story?How widely will your research appeal? To researchersin the same field or to the broader scientificcommunity?

    Journal Selection

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    Publishing frequencyImpact factorTarget audienceAims and scopeRejection rate

    Lead times

    Access (open or subscriber)Prior publicationsPublication feesPublication types

    What should you consider?

    How do these relate to your publication needs?

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    Journal Selection

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    Unethical behavior could lead to rejection and a possibleban from a target journal.

    Multiple submissionsRedundant publicationsPlagiarismData fabrication and falsificationImproper use of human subjects and animals inresearchImproper author contribution

    Publication ethics

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    The write orderTitleAbstract and keywordsIntroductionMaterials and Methods

    ResultsDisplay itemsStatisticsDiscussion andConclusionsReferences

    Section Two Manuscript structure

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    IMRaD manuscripts: for maximum clarity andconsistency, write in this order:

    Methods

    ResultsIntroduction

    Discussion

    Title

    Abstract

    Write after selecting your

    target journal

    Write during the research

    The write order

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    Hook to catch

    readers

    Sells yourmanuscriptto the editor

    Relevant readersincrease citations

    Journal editors like citations

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    The importance of your title

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    Convey the main findings of the research

    Be specific and concise without focusing on only

    one part of the contentAvoid jargon, non-standard abbreviations andunnecessary detail

    Comply with character limits

    Some journals also require a short running title

    A good title

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    Poor

    Degeneration of neurons in the CA3 and DG followingOA administration: involvement of a MAPK-dependent

    pathway in regional-specific neuronal degeneration

    Better

    Region-specific neuronal degeneration after okadaicacid administrationMAP kinase-dependent neuronal degeneration afterokadaic acid administration

    Edanz Group Ltd. | 18

    A good title

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    Edanz Group Ltd. | 19

    A good title

    Development of pharmacotherapies for drugaddiction: a Rosetta Stone approach

    Reprogramming bacteria to seek and destroy anherbicide

    Stress, memory and amygdala

    Tumor-host cell interactions in the bone diseaseof myeloma

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    Many researchers will only read the abstract somust be able to stand alone

    Must give an accurate summary of your research,

    and enough information so that readers canunderstand:

    What you did

    Why you did itWhat your findings areWhy your findings are useful and important

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    Abstract

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    General rules for abstracts:

    Within the word limit

    Avoid technical jargon

    Avoid abbreviations unless necessary

    Avoid references

    Structured or unstructured?

    Always consult the target journals Guide for Authors todetermine allowable length, style and abbreviations

    Edanz Group Ltd. | 21

    Abstract

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    Edanz Group Ltd. | 22

    Abstract Structured Risk factors and mortality in patients with nosocomial staphylococcus aureus bacteremia

    BACKGROUND:Infections due to methicillin-resistant Staphylococcus aureus have becomeincreasingly common in hospitals worldwide. S aureus continues to be a cause of nosocomial bacteremia.METHODS: We analyzed the clinical significance (mortality) of MRSA and methicillin-susceptible S aureus bacteremia in a retrospective cohort study in a 2900-bed tertiaryreferral medical center. Survival and logistic regression analyses were used to determinethe risk factors and prognostic factors of mortality.

    RESULTS:During the 15-year period, 1148 patients were diagnosed with nosocomial Saureus bacteremia. After controlling potential risk factors for MRSA bacteremia on logisticregression analysis, service, admission days prior to bacteremia, age, mechanical ventilator,and central venous catheter (CVC) were independent risk factors for MRSA. The crudemortality rate of S aureus bacteremia was 44.1%. The difference between the mortalityrates of MRSA (49.8%) and MSSA bacteremia (27.6%) was 22.2% (P < .001). Upon logisticregression analysis, the mortality with MRSA bacteremia was revealed to be 1.78 timeshigher than MSSA (P < .001). The other predicted prognostic factors included age,

    neoplasms, duration of hospital stay after bacteremia, presence of mechanical ventilator,and use of CVC.CONCLUSIONS:Resistance to methicillin was an important independent prognostic factorfor patients with S aureus bacteremia.

    PMID: 18313513 [PubMed - indexed for MEDLINE]; Am J Infect Control. 2008Mar;36(2):118-22.

    2 sentences

    2 sentences

    5 sentences

    1 sentence

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    Abstracts are often followed by a list of keywordsselected by the authors

    Choosing appropriate keywords is important forindexing purposesYour manuscript can more easily identified,read and citedKeywords should be specific to your manuscriptGeneral terms should be avoidedMany medical journal require MeSH terms

    Edanz Group Ltd. | 23

    Keywords

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    Manuscript title:Region-specific neuronal degeneration after okadaic acidadministration

    Poor keywords:

    neuron, brain, OA (as an abbreviation), regional-specificneuronal degeneration, signaling

    Better keywords:

    okadaic acid, hippocampus, neuronal degeneration,MAP kinase signaling

    Edanz Group Ltd. | 24

    Keywords

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    Must give the reader enough background informationto put your work into contextEnough information to understand the rationale foryour study is all that is requiredDo not write a comprehensive literature review of thefieldDo cite reviews that readers can refer to if they wantmore information

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    Introduction

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    Define technical and non-familiar terms

    Present the problem, research question and/or

    hypotheses to explain the rationale for the studyBriefly explain how you addressed this problemand what was achieved (1 2 sentences for each)

    Citations must be balanced, current and relevant

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    Introduction

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    IntroductionLiver resection has become an increasingly safe procedure, but certainprocedures remain high risk, such as massive liver resection and small-for-size (SFS) liver transplantation. Massive hepatic resection is the only optionfor some patients.

    The failure of a partial liver to regenerate is considered a critical contributingfactor in postsurgical primary liver dysfunction and liver failure, and minimalviable liver volume required for regeneration, following either massive liver

    resection or SFS transplantation, is an important concept...

    Thus, although the studies outlined above indicate that complementinhibition represents a potential therapeutic strategy to protect againsthepatic IRI, the important role of complement in liver regeneration wouldappear to be a contraindication for such a strategy in the context of liverresection and SFS liver transplantation, even though IRI is associated withimpaired regeneration

    In the current study, we investigated the role of complement in therelationship between hepatic IRI and liver regeneration using 3 murinemodels: a warm total hepatic IRI model (similar to the Pringle maneuver), a70% PHx model, and a combined IRI/PHx model designed to recreate clinicalmassive liver resection under the Pringle maneuver. In these studies, weused the complement inhibitor CR2 complement component

    Edanz Group Ltd. | 27

    A complement-dependent balance between hepaticischemia/reperfusion injury and liver regeneration in mice

    Songqing He, Carl Atkinson, Fei Qiao, Katherine Cianflone, Xiaoping Chen and Stephen Tomlinson

    The Journal of Clinical Investigation (doi:10.1172/JCT38289; reproduced with permission)

    Statement of the problem

    Background

    Rationale

    What was done

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    Clear subheadings for methods/materialsDescribe methods in the past tense

    Novel methods must be described in sufficient detailfor a capable researcher to reproduce the experiment

    Give manufacturers/suppliers and their locations

    Describe any statistical tests used

    Established methods can be referenced

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    Materials and methods What you did

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    Edanz Group Ltd. | 29

    Proapoptotic signaling induced by RIG-I and MDA-5 results in type Iinterferon-independent apoptosis in human melanoma cells.

    Robert Besch, Hendrik Poeck, Tobias Hohenauer et al.

    Reagents and antibodies. Anti caspase-3, anti caspase-8 (1C12), anti caspase-9, anti Bcl-xL, anti Bcl-w,and HRP-conjugated secondary antibodies were obtained from New England Biolabs. Anti cytochrome c(clone 7H8.2C12) was from BD Biosciences. Anti-Noxa (N-15) antibody was from Santa Cruz BiotechnologyInc. Anti Bcl-2 (Ab-1) and anti-p53 (Ab-6) antibodies were from Merck Biosciences. Anti IPS-1 antibodywas obtained from Bethyl Laboratories Inc. Anti -actin (AC-15) and anti-Puma (bbc3) antibodies werepurchased from Sigma-Aldrich. PCR primers and siRNAs were purchased from MWG Biotech.

    Immunostimulatory and siRNAs. Poly(I:C) was purchased from Amersham Biosciences. 5 -Triphosphate conjugated RNAs (pppRNAs) were transcribed in vitro from DNA templates as described in ref. 6. Theycontained a T7 RNA Polymerase consensus promoter sequence followed by the sequence of interest to betranscribed (MEGAshortscript Kit; Ambion). Reactions were treated with DNAse I (Ambion

    siRNAs were designed according to published guidelines (48, 49) 3 Overhangs were carried out as twodeoxythymidine residues (dTdT).Sequences of specific siRNAs are listed in Supplemental Table 1.Nonsilencing control siRNAs were designed to contain random sequences that do not match within thehuman genome...

    Cell culture. Human melanoma cell lines were a gift of M. Herlyn (Wistar Institute, Philadelphia,Pennsylvania, USA)

    Analysis of lung metastasis. For metastasis analysis at day 10, we isolated genomic DNA from lungs.Mouse lungs were reduced to small pieces and digested overnight at 56

    C in a buffer containing 10 mMTris, pH 8.0, 100 mM NaCl, 1 mM EDTA, 1% SDS, 0.5 mg/ml Pronase E (Sigma-Aldrich), and 150 g/mlProtease K (Sigma-Aldrich). Genomic DNA was purified by phenol/chloroform extraction. The amount of human and murine DNA was determined by quantitative PCR using the LightCycler TaqMan Master Kit(Roche) together with the Universal Probe Library system (Roche). A 72-bp portion in the second intron of the human -actin

    Statistics. For statistical analysis, 2- tailed Students t test was used to assess the significance of meandifferences. Differences were considered significant at a P value of 0.05 or less.

    Materials

    describedfirst

    Referencesto savespace

    Clearsubheadings

    Detailedinformationgiven

    Suppliers

    Statisticaltestinformation

    The Journal of Clinical In vestigation (doi:10.1172/JCI37155; reproduced with permission)

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    Assemble your findings in a logical order to make a storyPresent your findings in subsections (the same as those in yourmethods section)

    Present complementary evidence when possible

    Describe results in the past tenseRefer to figures and tables in the present tense

    Do not discuss implications do that in the discussion sectionDo not duplicate data among figures, tables and text

    Show the results of statistical analyses, ( e.g., p values) in thetext

    Edanz Group Ltd. | 30

    Results What did you find?

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    Edanz Group Ltd. | 31

    Proapoptotic signaling induced by RIG-I and MDA-5 results in type Iinterferon independent apoptosis in human melanoma cells

    Robert Besch, HendrikPoeck et al

    pppRNA and poly(I:C) induce apoptosis in melanoma cells.We tested the ability of RIG-I and MDA-5 ligands to induce cell death in human melanoma cell lines. Five celllines derived from advanced melanomas (vertical growth phase or metastatic origin) were analyzed.Activation of RIG-I and MDA-5 by pppRNA1 and poly(I:C) strongly reduced viability from 100% in controls to20% 50% within 24 hours (Figure (Figure1A). 1 A). Viability was reduced due to induction of apoptosis asdetermined by staining with annexin V. Apoptosis strictly required intracellular delivery, as neither pppRNAsnor poly(I:C) without transfection were active (Figure (Figure1B). 1 B). Different pppRNAs were tested, and allreduced cell viability (Figure (Figure1C). 1 C). The 5 -triphosphate moiety was required, since synthetic RNAscarrying a free OH group at the 5 end (e.g., OH -RNA1) had no effect (Figure (Figure1C, 1 C, left panel) . Strongdose-dependent reduction of viability was observed for poly(I:C) (Figure (Figure1C, 1 C, right panel) . Reducedviability was reflected in an increased number of cells undergoing apoptosis (Figure (Figure1D). 1 D).Confirming the onset of apoptosis, caspase-3 was activated in cells transfected with pppRNAs or poly(I:C) butnot in cells exposed to pppRNA or poly(I:C) in the absence of transfection reagent (Figure (Figure1E). 1 E).Together, these results show high sensitivity of human melanoma cell lines toward apoptosis induction bypppRNAs or poly(I:C) when delivered to the cytosol.

    Apoptosis induction by pppRNA and poly(I:C) involves IPS-1 but is independent of IFN signaling.The RNA ligands pppRNA and poly(I:C) both induced IFN- expression in melanoma cells

    (Figure (Figure3A).3A). Silencing of RIG -I and MDA-5 confirmed that induction of IFN- by pppRNA andpoly(I:C) required RIG-I and MDA-5, respectively, and that both required

    Melanoma cells are more sensitive to RIG-I and MDA-5 induced apoptosis than primary cells.We next compared healthy primary cells of the skin with melanoma cells to evaluate tumor specificity of apoptosis induction by RIG-I and MDA-5. Primary human melanocytes, primary fibroblasts, and primarykeratinocytes were significantly less sensitive to pppRNA and poly(I:C) compared with melanoma cells(Figure (Figure7A).7A).

    Graphics used toshow data withonly brief descriptions intext

    Clearsubheadings

    It is clear whatwas comparedwith what

    The Journal of Clinical Investigation (doi:10.1172/JCI37155; reproduced with permission)

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    Some readers will only look at the figures and their legendsFigures and tables are the best way to present your resultsData shown in figures and tables must be easy to interpret use separatepanels if necessary

    Avoid redundancies or duplication

    Clearly label all components

    Show trendlines, scale bars and statistical significance

    Legends must be able to stand alone: write them in the present tense(except when describing methods)

    Comply with journal guidelines on display items

    Edanz Group Ltd. | 32

    Display items Tables and figures

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    Tables are a great way to present large amounts of necessarydata with minimal description required

    Part of a table in a paper published in The Journal of Clinical Investigation (doi:10.1172/JCI37622; reproduced with permission)

    Edanz Group Ltd. | 33

    Display items Tables and figures

    Clear concise heading

    Data divided intocategories forclarity

    Percentages as well asabsolute values

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    Edanz Group Ltd. | 34

    Display items Tables and figuresTrend lines

    Multi-panel:different kinds of

    data groupedtogether in a singlefigure

    Complicated dataseparated into

    simpler components

    Scale bars

    Figure 5RCP knockdown attenuatestumor formation and metastasis.Effects of RCP inhibition ontumor growth using (A) MCF7cells in nude mice and (B) MB231cells in NOD-SCID mice areshown. (A) Left panel showsmean tumorvolume plotted as afunction of time (mean SEM).

    Right panel shows tumor weightplotted at 5 weeks; mean weightindicated by solid line. (B) Leftpanel, tumor weight plotted atindicated number of weeks;mean weight indicated by solidline. Right panel, the averagenumber of lung micrometastasesper section is shown. (C)Representative lung sections andfluorescently imaged whole lungs(right panel) of NOD-SCID miceare shown. Micrometastases are

    indicated by arrows. Scale bars:200 m .

    Clear, standalone legend

    The Journal of Clinical Investigation (doi:10.1172/JCI37622; reproduced with permission)

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    Edanz Group Ltd. | 35

    Statistics

    A man has one hand in boiling water

    The other hand in freezing water

    He is comfortable on average

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    Today, few professional activities are untouched bystatistical thinking, and most academic disciplines use it Statistical thinking is a way of recognizing that our

    observations of the world can never be totally accurate ;they are always somewhat uncertain

    Rowntree D (1981). Statistics without tears. A primer for non-mathematicians. Penguin Books Ltd., London,England

    Edanz Group Ltd. | 36

    Statistics

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    Statistical analysis is at the heart of scientific inquiryConsider statistical analysis when you design yourstudy. Before you start your research.

    Edanz Group Ltd. | 37

    Statistics

    Datacollection

    Dataanalysis Interpretation

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    Edanz Group Ltd. | 38

    Statistics Poor statisticsPoor statistics

    Poor studydesign

    e.g., samplesize is too small

    Poor analysis

    Data are valid

    Re-analysis or re-interpretation

    Revise manuscript

    Difficult to recover

    Poor interpretation

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    Reporting statistics in your manuscript:

    Consult a statistical expert about which test to use!Clearly describe the statistical tests used to analyzedataGive the software, version number and makerOnly use the word significant when describing

    statistically significant differences Alternatives: notable, substantial, marked P not enough for significant? Describe as a trend

    Edanz Group Ltd. | 39

    Statistics Basics

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    Edanz Group Ltd. | 40

    Statistics Questions

    Ask yourself these questions during study design:

    What are the independent and dependent variables?What is the scale of measurement of the studyvariables?Consider sample number for power analysisi.e., how many samples will you need?

    Have I met the assumptions of the statistical testselected?

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    Edanz Group Ltd. | 41

    Statistics Details

    Reporting statistics in your manuscript:

    Indicate the parameters described, e.g., means S.DGive the numerator and denominator withpercentages, e.g., 40% (100/250)Report p values, e.g., use p=0.0035 rather thanp

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    Edanz Group Ltd. | 42

    Statistics A few rules

    Use appropriate amount of precision:Life expectancy of 22.085 years 22 yearsData should be rounded when presented NOT when analyzedAlways give numerator and denominator. E.g., 25% (650/2958)Avoid using percentages to summerise small samplesBe very clear with percentages within subgroups:Of the 1000 patients, 800 (80%) were women; (31%) had a BMIof

    BookAs a full guide see the excellent book:How to report statistics in medicineby Thomas A. Lang and Michelle Secic (ACP Press, Second Edition)

    Of the 1000 patients, 800 (80%) were women; of these, 250 (31%)

    had a BMI of

    A complement dependent balance between hepatic ischemia/reperfusion injury

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    Figure 7Opposing effects of high- and low-dose complement inhibition on hepatic injury and regeneration in a model incorporating both IRIand PHx. Mice were treated with normal saline or CR2-Crry at a dose of either 0.25 mg or 0.08 mg immediately after surgery. C3 /

    mice received no treatment. All determinations made 48 hours after I/R and PHx. ( A) Mouse survival. ( B) Serum ALT levels. ( C)Histological quantification of hepatic necrosis and injury determined on a scale of 0 4. (D) Assessment of regeneration by BrdUincorporation. ( E) Restitution of liver weight. ( F) MPO content in liver samples . #P < 0.05, ##P < 0.01 versus WT group; ** P < 0.01versus WT group (similar to WT normal saline group); P < 0.01 versus all other groups; * P < 0.05, ** P < 0.01 versus WT group.Results are expressed as mean SD; n = 6 10.

    A complement-dependent balance between hepatic ischemia/reperfusion injuryand liver regeneration in mice

    Songqing He, Carl Atkinson et al

    Edanz Group Ltd. | 43

    The Journal of Clinical Investigation (doi:10.1172/JCI38289; reproduced with permission)

    Statistics. Data are expressed as mean SD. Significantdifferences between groups were determined by ANOVA, witha Bonferroni correction for continuous variable and multiplegroups. Two- tailed Students t test was used for thecomparison of a normally distributed continuous variablebetween 2 groups. For the survival studies, Kaplan-Meier log-rank analysis was performed. P values of less than 0.05 were

    considered statistically significant.

    ALT levels were significantly lower at 24 and 48 hours after PHx inlow-dose CR2-Crry treated mice compared with those in saline-treated controls.Compared with WT mice, surviving C3 / mice had significantlyincreased hepatic injury and an impaired proliferative response(Figure 7, B E)...

    Methods Results

    Data type defined Statistical tests clearly described

    significant only used forstatistical significance

    Significance indicated in figure/table legend

    Significance threshold defined

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    Restate your research question and/or any hypothesespresented in the introductionSummarize your main findings make it clear how yourstudy has advanced the field

    Begin with your most important findingPast tense to describe results (current and published)Present tense to describe their implications

    Minimize repetition with other sectionsDescribe inconsistencies with other papersDescribe the limitations of your study

    Edanz Group Ltd. | 44

    Discussion What does it all mean?

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    Be humbleDont overstate the importance of your results

    Our findings prove that

    Our findings show that

    Our findings suggest that

    Edanz Group Ltd. | 45

    Discussion

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    Restate key findings and their significance

    Propose future studies that might follow on from yourcurrent study

    Give the reader a take -home message

    Edanz Group Ltd. | 46

    Conclusions

    we can now conduct quantitative and functional genetic studies in naturalpopulations ( Science )

    Hopefully, more prospective, randomized, clinical trials will address theseconcerns and reinforce the efficacy of tropical antimicrobial therapy (CurrInfect Dis Rep)

    further, the structures reported here highlight the complex network of protein -protein and protein- DNA interaction (Nature )

    RCP is h m n bre st c ncer promoting gene ith R s cti ting f nction

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    DiscussionGenome-wide microarray analysis of primary tumors has enabled the discovery of novel, clinicallyrelevant tumor subtypes defined by unique patterns of gene expression. More recently, however,

    the inverse of this concept has been explored through bottom-up analytical strategies that seek toidentify gene subtypes with functional roles in tumorigenesis

    In the present work, we have built on this concept of data integration and functional discovery andidentified RCP, located on the 8p11 12 recurrent breast cancer amplicon, as a novel breast-cancerpromoting gene with Ras- activating potential.

    Amplification of the 8p11 12 locus has been observed in approximately 10% 25% of breast tumorcases and 15% of breast cancer cell lines and has been associated with poor patient survival andshort interval to distant metastasis. Recently, this amplicon has been the focus of several

    functional genomics investigations involving primary breast tumors and cell lines. Using a high-resolution BAC microarray specific for chromosome 8p, Gelsi- Boyer and colleagues

    However, that the growth and metastatic properties of the tumor xenografts were dependent onthe endogenous expression of RCP suggests an oncogene addiction like scenario, whereby RCPmay play a vital role in the maintenance and potentiation of the malignant and metastaticphenotype

    In conclusion, through integrated genomic analysis, we identified RCP as a candidate oncogene atthe 8p11 12 amplicon, with expression levels significantly correlated with aggressive breastcancer behavior

    The broader involvement of RCP in the pathogenesis of human cancers and the mechanismsunderlying its oncogenic effects will be the focus of future investigations .

    RCP is a human breast cancer promoting gene with Ras-activating functionJinqiu Zhang, Xuejing Liu et al

    The Journal of Clinical Investigation (doi:10.1172/JCI37622; reproduced with permission)

    Edanz Group Ltd. | 47

    Restate the

    question/problem

    Restate main findings

    Put in context of

    previous work

    Future research plans

    Use suggests and may

    Restate main findings

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    Always format your references: check your target journalsGuide for Authors for the appropriate format

    Harvard style or Vancouver style or APA

    Formatting is required both in text and in the referencessection

    Use a reference manager like Endnote. Makes it easy toedit, reformat, add or remove references

    Some journal limit the number of references: check yourtarget journals Guide for Authors

    Edanz Group Ltd. | 49

    References

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    Your cover letterRecommending reviewers

    LanguageGood writingCommon language problems

    What do reviewers look for?Submission

    Final checksPost-referee revisionsChecklist

    Section Three Tips for getting accepted

    Edanz Group Ltd. | 50

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    Cover letters

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    Journal Editors receive hundredsof manuscripts each monthThey dont have time to read eachmanuscriptSociety journal editors areespecially busy as they are usuallypracticing researchers too

    Your cover Letter is an opportunityto get the journal editors attention

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    Competition for publication space and for editorsattention is very highIt is not enough to send a manuscript to a journal editorlike this:

    Cover letters

    Edanz Group Ltd. | 52

    Dear Editor-in-Chief,

    I am sending you our manuscript entitled Large Scale Analysis of Cell Cycle Regulators inbladder cancer by A. Honda, K. Tanaka, J. Suzuki, and myself. We would like to have themanuscript 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

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    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 results

    Explain why your findings are important and why they would beof interest to the journals target audience

    Consult the journals Guide for Authors for cover letter

    requirements ( e.g., disclosures, statements, potential reviewers)Give corresponding author details

    Your cover letter

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    Dear Dr Lisberger,

    Please find enclosed our manuscript entitled Amyloid- like inclusions in the brains of Huntingtons disease patients, byMcGowan et al., which we would like to submit for publication as a Research Paper in Neuroscience .

    Recent immunohistochemical studies have revealed the presence of neuronal inclusions containing an N-terminal portionof the mutant huntingtin protein and ubiquitin in the brain tissues of Huntingtons disease (HD) patients; however, the roleof these inclusions in the disease process has remained unclear. One suspected disease-causing mechanism inHuntingtons disease and other polyglutamine disorders is the potential for the mutant protein to undergo aconformational change to a more stable anti-parallel -sheet structure

    To confirm if the immunohistochemically observed huntingtin- and ubiquitin-containing inclusions display amyloidfeatures, we performed Congo red staining and both polarizing and confocal microscopy on post-mortem human braintissues obtained from five HD patients, two AD patients, and two normal controls. Congo red staining revealed a smallnumber 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 HDadopt an amyloid-like structure.

    We believe our findings would appeal to a broad audience, such as the readership of Neuroscience . 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. Allauthors have approved the manuscript and agree with submission to Neuroscience . We have read and have abided by thestatement of ethical standards for manuscripts submitted to Neuroscience . The authors have no conflicts of interest todeclare.

    Please address all correspondence to.

    Give thebackground tothe research

    Explain whatwas done andwhat was found

    Explain why thisis interesting tothe journalsreadership

    Conforms tothe journalsrequirements

    Your cover letter

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    RecommendYour work supports their hypotheses and ideas

    Your research builds on their work

    International collaborators in the same fieldExclude

    Researchers working on the same research question

    Your study refutes their workThe findings in your manuscript are are opposite to theirfindings or ideas

    Reviewers Recommendations and exclusions

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    Journal editors are overloaded with quality manuscripts.They may make decisions on manuscripts based onformal criteria, like grammar or spelling.Don't get rejected for avoidable mistakes: make sureyour manuscript looks perfect

    Language

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    A senior executive at a large international publishing house

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    Introduction of languagescreening protocols to

    check submissions

    Editors dont want to send poorly written manuscripts forpeer reviewEditors receive enough well written submissions to rejectpoorly written manuscripts

    Language screening

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    Language

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    Some journals are very clear regarding their English requirements,and about what happens to manuscripts that do not meet theirstandards

    European Polymer Journal

    Language and Style: Manuscripts should bewritten in English in a clear and concise manner.

    Manuscripts which are not written in fluent

    English will be rejected automatically withoutrefereeing.

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    Clarity

    ConcisenessCorrectness (accuracy)

    Good scientific writing possesses the following three Cs :

    Key points:Be as brief as possible without omitting essential details

    Be as specific as possible

    Scientific writing

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    Avoid:Spelling and grammatical errors

    Insufficient detail/vagueness

    Repetition

    Redundancy

    Ambiguity

    Inconsistency

    They annoy editors, peer reviewers and readers

    Scientific writing Common problems

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    TenseArticlesPlural or singular

    Proper nounsHyphen or dashThat/whichMaking comparisonsRespectivelyBetween or among

    NomenclatureSuch as/namelyEtc.

    Asian fontsUK or US spellingPresenting numbers

    Language Common English problems

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    Language Dash or hyphen

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    Hyphen (-): for joining usually separate words

    Incorrect use can lead to ambiguity

    twenty-four hour reactions

    twenty four-hour reactions

    is different to

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    Language Dash or hyphen

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    En dash ( ): means through.October 28 29; pp. 2 5. (dont use ~)

    Em dash (): Used to break a sentence, introducesomething, or introduce an afterthought.These two metals that is, titanium and magnesium are very light.

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    Language Asian fonts

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    Be careful of Asian fonts such as MS Mincho and SimSumDo not use Asian fonts in your manuscripts

    For example:

    Why not?

    Because they look like this on some computers: or ?

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    Use simple language: it is often clearer, more precise andmore 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

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    Language UK or US spelling

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    Be consistent

    Check the journals Guide for Authors

    Generally, American journals require US spelling and British journals require British spelling, but many accept either formas long as the spelling used is consistent

    fibre or fiber

    centre or center

    labelling or labelingcolour or color

    Exceptions: Ministry of Health, Labo ur and Welfare; your references

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    Language Comparisons

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    Frequently made in the results sections of papersCompare like with like

    Do not be vague

    Use with , not to

    The material from the river bank was compared with thelandfill.

    The material from the river bank was compared with thatfrom the landfill.

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    Language Comparisons

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    Expression levels of p53 in smokers were compared with non-smokers

    Expression levels of p53 in smokers were compared with p53levels in non-smokers

    Expression levels of p53 in smokers were compared withthose in non-smokers

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    69

    Language Comparisons

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    Relative terms, such as more, higher and greater, require areference for comparison

    Use than or compared with

    Reactions with the new machine were faster than those with theold machine.

    Reactions with the new machine were faster. than what?

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    Language Between or among

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    Use between for comparisons of two groups

    Use among for comparisons of more than two groups

    ..significant differences were observed in the H values among bio-, fully- and semi- synthetic

    the only difference between the original molecule and the newmolecule is...

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    Language Respectively

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    Use to refer to two corresponding lists, but not moreFor example:

    Oxygen detector flow Nitrogen detector flow Hydrogen detector flow

    85 mL/min 7 mL/min 4 mL/min

    Oxygen, Nitrogen and Hydrogen detector flows were set at85, 7 and 4 mL/min, respectively.

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    Language Presenting numbers

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    AMA Manual of Style is a good guide:Spell out numbers one through nine, numerals for 10 and up

    EXCEPTUnits of measurement, times, and dates: 2 mL; 1996

    Beginning of a sentence

    Fifteen days previouslyNOT: 15 days previouslyA mixture of numbers in one sentence:The sample included 34 men with type A blood, 15 with type Band 3 with type AB.

    Differentiating consecutive numbers:Five, 50- kg women.NOT 5, 50 -kg women

    Large numbers in general expressions:A hundred; several thousand.

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    Language Presenting numbers

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    SpacingNo space between numeral and percent sign: 48%Space between numeral and unit of measurement: 178 mm

    Decimals

    Use zero before decimal: 0.28 mL BUT Not when reporting P values: P= .04

    Rates, proportions and fractionsUse the virgule (/) for proportions, colon (:) for ratiosAbout 1/3 of samples the ratio was 3:4.5The rate averaged 40/100,000 people BUT Spell out noun-modifying fractions:Half the cases showed..; a two -thirds majority

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    Language Such as or namely

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    such as: to give examples

    namely: to define

    .there were other factors, such as nutrient status, primaryproduction, microbial biomass, and coagulation processes.

    we used certified reference materials, namely C36 n -alkane andphenanthrene , obtained from

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    Language Colon or semi-colon

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    The colon : is used to introduce a list or a clause thatexplains what precedes it

    Semicolon ; is used to separate the items in a list too longfor commas or where commas could be ambiguous. Useand before the last item in the list.

    There are a number of journals for surgery manuscripts :Surgery, produced by Elsevier ; Journal of Surgery, producedby NMS; British Journal of Surgery

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    Language Colon or semi-colon

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    Use a semicolon to join two sentences that are not independent

    In previous sediments of all salinities, MeHg production washighest at previous sediment depths just below the oxic/anoxic

    transition ; that is, depths where microbial sulfate reduction waspresent, but where sulfide, which inhibits methylation, wasrelatively low.

    One sentence is too long ; but the two sentences must be connected

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    Language Minimizing errors

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    The internet can help youGoogle Scholar to check for word usageCheck your target journals home page for full instructions

    MS Word

    Track changes functionComment functionFind (and replace) to check for consistencyWord Count functionSpell Check (but be careful)Custom Dictionaries (provided by some academic societies forspecific fields)Online glossaries provided by academic societies

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    Is the manuscript sufficiently novel?Is the manuscript of broad enough interest?

    Reviewers What do they look for?

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    NoveltySignificance

    Aims and ScopeImpact Factor

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    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?

    Reviewers About the research

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    Reviewers About the manuscript

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    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?

    b

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    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 appropriateresolution or size?

    Is your spelling/grammar correct?Do you have contact information for all authors?

    Have you completed online registration?

    Or have you prepared the requested number of print copiesplus CD?Have you written a persuasive cover letter?

    Submission Final checks

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    R i i

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    Rejection from journals is an important part of thepublication processIt is not a negative experience

    It exists to ensure that your paper is as scientificallyrobust and complete as possible before joining thecollective knowledge as part of the literature

    Revisions Post-referee revisions

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    R i i

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    Only 1.5% of papers are immediately accepted withoutneed for any revisions

    Journal editordecision

    Complete rejection

    Acceptance

    Rejection with major revisions

    Rejection with minor revisions

    Revisions Post-referee revisions

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    R i i

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    Revisions Post-referee revisions

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    When revising your manuscript:

    Address all points raised by the editor and/or reviewersDescribe the revisions in your response letterPerform any additional experiments or analyses requested

    (unless you feel that they would not add to the strength of yourpaper: explain why not in your response letter)Provide a polite and scientific rebuttal to any points or commentsyou disagree with

    Differentiate comments and responses in your letterClearly show the major revisions in the textReturn revised manuscript and response letter within therequested time period

    S

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    Appropriate study designCompliance with ethics guidelinesAppropriate statistical tests

    Novel and interesting resultsClear, concise, accurate writingCompliance with the Guide for Authors

    Significance of findings explainedAppropriate choice of journal

    Summary Checklist for acceptance