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1.  Evaluating adherence to the International Committee of Medical Journal Editors’ policy of mandatory, timely clinical trial registration 
Objective
To determine whether two specific criteria in Uniform Requirements for Manuscripts (URM) created by the International Committee of Medical Journal Editors (ICMJE)—namely, including the trial ID registration within manuscripts and timely registration of trials, are being followed.
Materials and methods
Observational study using computerized analysis of publicly available Medline article data and clinical trial registry data. We analyzed a purposive set of five ICMJE founding journals looking at all trial articles published in those journals during 2010–2011, and data from the ClinicalTrials.gov (CTG) trial registry. We measured adherence to trial ID inclusion policy as the percentage of trial journal articles that contained a valid trial ID within the article (journal-based sample). Adherence to timely registration was measured as the percentage of trials that registered the trial before enrolling the first participant within a 60-day grace period. We also examined timely registration rates by year of all phase II and higher interventional trials in CTG (registry-based sample).
Results
To determine trial ID inclusion, we analyzed 698 clinical trial articles in five journals. A total of 95.8% (661/690) of trial journal articles included the trial ID. In 88.3% the trial-article link is stored within a structured Medline field. To evaluate timely registration, we analyzed trials referenced by 451 articles from the selected five journals. A total of 60% (272/451) of articles were registered in a timely manner with an improving trend for trials initiated in later years (eg, 89% of trials that began in 2008 were registered in a timely manner). In the registry-based sample, the timely registration rates ranged from 56% for trials registered in 2006 to 72% for trials registered in 2011.
Discussion
Adherence to URM requirements for registration and trial ID inclusion increases the utility of PubMed and links it in an important way to clinical trial repositories. This new integrated knowledge source can facilitate research prioritization, clinical guidelines creation, and precision medicine.
Conclusions
The five selected journals adhere well to the policy of mandatory trial registration and also outperform the registry in adherence to timely registration. ICMJE's URM policy represents a unique international mandate that may be providing a powerful incentive for sponsors and investigators to document clinical trials and trial result publications and thus fulfill important obligations to trial participants and society.
doi:10.1136/amiajnl-2012-001501
PMCID: PMC3715364  PMID: 23396544
clinical trials as topic/legislation; registries; cross-sectional analysis; Databases; publication policy; trial registration
2.  The publication of ethically uncertain research: attitudes and practices of journal editors 
BMC Medical Ethics  2012;13:4.
Background
Publication of ethically uncertain research occurs despite well-published guidelines set forth in documents such as the Declaration of Helsinki. Such guidelines exist to aide editorial staff in making decisions regarding ethical acceptability of manuscripts submitted for publication, yet examples of ethically suspect and uncertain publication exist. Our objective was to survey journal editors regarding practices and attitudes surrounding such dilemmas.
Methods
The Editor-in-chief of each of the 103 English-language journals from the 2005 Abridged Index Medicus list publishing original research were asked to complete a survey sent to them by email between September-December 2007.
Results
A response rate of 33% (n = 34) was obtained from the survey. 18% (n = 6) of respondents had published ethically uncertain or suspect research within the last 10 years. 85% (n = 29) of respondents stated they would always reject ethically uncertain articles submitted for publication on ethical grounds alone. 12% (n = 4) of respondents stated they would approach each submission on a case-by-case basis. 3% (n = 1) stated they would be likely to publish such research, but only with accompanying editorial. Only 38% (n = 13) give reviewers explicit instruction to reject submissions on ethical grounds if found wanting.
Conclusions
Editorial compliance with the Declaration of Helsinki in rejecting research that is conducted unethically was difficult to ascertain because of a poor response rate despite multiple attempts using different modalities. Of those who did respond, the majority do reject ethically suspect research but few explicitly advise reviewers to do so. In this study editors did not take advantage of the opportunity to describe their support for the rejection of the publication of unethical research.
doi:10.1186/1472-6939-13-4
PMCID: PMC3378458  PMID: 22494972
Editors; Ethics; Publication ethics
3.  What do letters to the editor publish about randomized controlled trials? A cross-sectional study 
BMC Research Notes  2013;6:414.
Background
To identify published letters to the editor (LTE) written in response to randomized controlled trials (RCTs), determine the topics addressed in the letters, and to examine if these topics were affected by the characteristics and results of the RCTs.
Methods
Comparative cross-sectional study of a representative sample of RCTs from a set of high-impact medical journals (BMJ, Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published LTE were searched from these 5 journals in 2007. Data were collected on RCTs and their characteristics (author affiliation, funding source, intervention, and effect on the primary outcome) and the topics addressed in published LTE related to these RCTs. Analysis included chi-square and regression analysis (RCT characteristics) and thematic analysis (LTE topics).
Results
Of 334 identified RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were identified. Most RCTs, tested drug interventions (68%), were funded by government (54%) or industry (33%), and described an intervention that had a positive impact on the primary outcome (62%). RCT authors were primarily affiliated with an academic centre (78%). Ninety percent of the 623 LTE topics concerned methodological issues regarding the analysis, intervention, and population in the RCT. There was a significant association between funding source and impact on outcomes (p = 0.002) or type of intervention tested (p = 0.001) in these trials. Clinical and “Other” LTE topics were more likely to be published in response to a government funded RCT (p = 0.005 and p = 0.033, respectively); no other comparisons were significant.
Conclusions
This study showed that most LTE are about methodological topics, but found little evidence to support that these topics are affected by the characteristics or results of the RCTs. The lack of association may be explained by editorial censorship as a small proportion of LTE that are submitted are actually published.
doi:10.1186/1756-0500-6-414
PMCID: PMC3852599  PMID: 24124753
Letters to the editor; Randomized controlled trials; Journalogy
4.  Kinetic Proofreading at Single Molecular Level: Aminoacylation of tRNAIle and the Role of Water as an Editor 
PLoS ONE  2013;8(6):e66112.
Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNAIle which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively), in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i) the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8×102).(4.33×102) = 7.8×104, (ii) the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNAIle. The present study shows a non-michaelis type dependence of rate of reaction on tRNAIle concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNAIle whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.
doi:10.1371/journal.pone.0066112
PMCID: PMC3688713  PMID: 23840412
5.  Vision Science and Schizophrenia Research: Toward a Re-view of the Disorder Editors’ Introduction to Special Section 
Schizophrenia Bulletin  2011;37(4):681-689.
This theme section on vision science and schizophrenia research demonstrates that our understanding of the disorder could be significantly accelerated by a greater adoption of the methods of vision science. In this introduction, we briefly describe what vision science is, how it has advanced our understanding of schizophrenia, and what challenges and opportunities lay ahead regarding schizophrenia research. We then summarize the articles that follow. These include reviews of abnormal form perception (perceptual organization and backward masking) and motion processing, and an article on reduced size contrast illusions experienced by hearing but not deaf persons with schizophrenia. These articles reveal that the methods of basic vision research can provide insights into a number of aspects of the disorder, including pathophysiology, development, cognition, social cognition, and phenomenology. Importantly, studies of visual processing in schizophrenia make it clear that there are impairments in the functioning of basic neural mechanisms (eg, center-surround modulation, contextual modulation of feedforward processing, reentrant processing) that are found throughout the cortex and that are operative in multiple forms of cognitive dysfunction in the illness. Such evidence allows for an updated view of schizophrenia as a condition involving generalized failures in neural network formation and maintenance, as opposed to a primary failure in a higher level factor (eg, cognitive control) that accounts for all other types of perceptual and cognitive dysfunction. Finally, studies of vision in schizophrenia can identify sensitive probes of neural functioning that can be used as biomarkers of treatment response.
doi:10.1093/schbul/sbr053
PMCID: PMC3122283  PMID: 21700588
schizophrenia; perception; vision; cognition; CNTRICS; RDoC
6.  Photoletter to the editor: Hyperkeratosis lenticularis perstans (Flegel's disease) with unusual clinical presentation. Response to isotretinoin therapy. 
Hyperkeratosis lenticularis perstans also known as Flegel's disease is a keratinisation disorder characterized by small keratotic papules with horny scales. Most cases have been reported in Europe with age of presentation between 35 and 60 years. We report a case of a 25-year-old man, who presented with 1-5 mm multiple asymptomatic hyperkeratotic papules of 15 years duration on both legs and hand along with lichenified plaques with Koebner phenomenon in the axillary folds, anticubital and popliteal fossae. Similar lesions were present in the eyelids also. There was no involvement elsewhere. Similar illness was found in the younger brother aged 13 years with the duration of illness for the past 5 years. Histopathology confirmed the clinical diagnosis. Patient was treated with oral isotretinoin in a daily dose of 20 mg per day to which he responded immediately with clearing of the lesions in two weeks.
doi:10.3315/jdcr.2012.1111
PMCID: PMC3470798  PMID: 23091588
Flegel's disease; hyperkeratosis lenticularis perstans; Koebner phenomenon; isotretinoin
7.  Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors 
Environmental Health  2013;12:69.
The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
doi:10.1186/1476-069X-12-69
PMCID: PMC3765603  PMID: 23981490
Endocrine disrupting chemicals; Environment; Health; Precautionary principle; Regulatory toxicology
8.  Photoletter to the editor: Diffuse cocaine-related purpura 
Diffuse purpura is an uncommon skin manifestation found in platelet and coagulation disorders, meningococcemia, vasculitides and cocaine use. Reports of cocaine-related purpura predominantly involve adulteration with the anti-helminthic, levamisole. Levamisole enhances the effects of cocaine and is known to cause vasculitis. Recently, the CDC also released an advisory of oxymorphone being used intravenously causing thrombogenic thrombocytopenic purpura (TTP). We report the case of a patient with diffuse purpura ultimately diagnosed with cocaine-related thrombogenic vasculopathy. In the current environment of adulterated cocaine usage and increased prescription narcotic abuse, it is crucial to investigate substance abuse as a cause of diffuse purpura.
doi:10.3315/jdcr.2013.1159
PMCID: PMC3888784  PMID: 24421868
cocaine; levamisole; oxymorphone; purpura
9.  A survey of the awareness, knowledge, policies and views of veterinary journal Editors-in-Chief on reporting guidelines for publication of research 
Background
Wider adoption of reporting guidelines by veterinary journals could improve the quality of published veterinary research. The aims of this study were to assess the knowledge and views of veterinary Editors-in-Chief on reporting guidelines, identify the policies of their journals, and determine their information needs. Editors-in-Chief of 185 journals on the contact list for the International Association of Veterinary Editors (IAVE) were surveyed in April 2012 using an online questionnaire which contained both closed and open questions.
Results
The response rate was 36.8% (68/185). Thirty-six of 68 editors (52.9%) stated they knew what a reporting guideline was before receiving the questionnaire. Editors said they had found out about reporting guidelines primarily through articles in other journals, via the Internet and through their own journal. Twenty of 57 respondents (35.1%) said their journal referred to reporting guidelines in its instructions to authors. CONSORT, REFLECT, and ARRIVE were the most frequently cited. Forty-four of 68 respondents (68.2%) believed that reporting guidelines should be adopted by all refereed veterinary journals. Qualitative analysis of the open questions revealed that lack of knowledge, fear, resistance to change, and difficulty in implementation were perceived as barriers to the adoption of reporting guidelines by journals. Editors suggested that reporting guidelines be promoted through communication and education of the veterinary community, with roles for the IAVE and universities. Many respondents believed a consensus policy on guideline implementation was needed for veterinary journals.
Conclusions
Further communication and education about reporting guidelines for editors, authors and reviewers has the potential to increase their adoption by veterinary journals in the future.
doi:10.1186/1746-6148-10-10
PMCID: PMC3922819
Veterinary journals; Veterinary research; Reporting guidelines; Reporting quality; Editors; Editorial policies; Views; Barriers
10.  An editor for pathway drawing and data visualization in the Biopathways Workbench 
BMC Systems Biology  2009;3:99.
Background
Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface.
Results
The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy) and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway) as well as from the LIPID MAPS web server . Data arises from metabolomic (lipidomic), microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language) contained in the local file system.
Conclusion
Inclusion of access to multiple experimental data types and of pathway diagrams within a single interface, automatic updating through connectivity to an online database, and a focus on annotation, including reference to standardized lipid nomenclature as well as common lipid names, supports the view that the Pathway Editor represents a significant, practicable contribution to current pathway modeling tools.
doi:10.1186/1752-0509-3-99
PMCID: PMC2763869  PMID: 19799790
11.  Skyline: an open source document editor for creating and analyzing targeted proteomics experiments 
Bioinformatics  2010;26(7):966-968.
Summary: Skyline is a Windows client application for targeted proteomics method creation and quantitative data analysis. It is open source and freely available for academic and commercial use. The Skyline user interface simplifies the development of mass spectrometer methods and the analysis of data from targeted proteomics experiments performed using selected reaction monitoring (SRM). Skyline supports using and creating MS/MS spectral libraries from a wide variety of sources to choose SRM filters and verify results based on previously observed ion trap data. Skyline exports transition lists to and imports the native output files from Agilent, Applied Biosystems, Thermo Fisher Scientific and Waters triple quadrupole instruments, seamlessly connecting mass spectrometer output back to the experimental design document. The fast and compact Skyline file format is easily shared, even for experiments requiring many sample injections. A rich array of graphs displays results and provides powerful tools for inspecting data integrity as data are acquired, helping instrument operators to identify problems early. The Skyline dynamic report designer exports tabular data from the Skyline document model for in-depth analysis with common statistical tools.
Availability: Single-click, self-updating web installation is available at http://proteome.gs.washington.edu/software/skyline. This web site also provides access to instructional videos, a support board, an issues list and a link to the source code project.
Contact: brendanx@u.washington.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/btq054
PMCID: PMC2844992  PMID: 20147306
12.  Avogadro: an advanced semantic chemical editor, visualization, and analysis platform 
Background
The Avogadro project has developed an advanced molecule editor and visualizer designed for cross-platform use in computational chemistry, molecular modeling, bioinformatics, materials science, and related areas. It offers flexible, high quality rendering, and a powerful plugin architecture. Typical uses include building molecular structures, formatting input files, and analyzing output of a wide variety of computational chemistry packages. By using the CML file format as its native document type, Avogadro seeks to enhance the semantic accessibility of chemical data types.
Results
The work presented here details the Avogadro library, which is a framework providing a code library and application programming interface (API) with three-dimensional visualization capabilities; and has direct applications to research and education in the fields of chemistry, physics, materials science, and biology. The Avogadro application provides a rich graphical interface using dynamically loaded plugins through the library itself. The application and library can each be extended by implementing a plugin module in C++ or Python to explore different visualization techniques, build/manipulate molecular structures, and interact with other programs. We describe some example extensions, one which uses a genetic algorithm to find stable crystal structures, and one which interfaces with the PackMol program to create packed, solvated structures for molecular dynamics simulations. The 1.0 release series of Avogadro is the main focus of the results discussed here.
Conclusions
Avogadro offers a semantic chemical builder and platform for visualization and analysis. For users, it offers an easy-to-use builder, integrated support for downloading from common databases such as PubChem and the Protein Data Bank, extracting chemical data from a wide variety of formats, including computational chemistry output, and native, semantic support for the CML file format. For developers, it can be easily extended via a powerful plugin mechanism to support new features in organic chemistry, inorganic complexes, drug design, materials, biomolecules, and simulations. Avogadro is freely available under an open-source license from http://avogadro.openmolecules.net.
doi:10.1186/1758-2946-4-17
PMCID: PMC3542060  PMID: 22889332
13.  Photoletter to the editor: Dermoscopy for discriminating between pityriasis rubra pilaris and psoriasis 
Pityriasis rubra pilaris (PRP) is a relatively uncommon entity that often has to be clinically differentiated from other erythematosquamous skin diseases, such as psoriasis. Dermoscopy has already been shown to enhance clinical evaluation of inflammatory skin conditions and dermoscopic patterns of various diseases, including psoriasis, have been documented. In the current manuscript we present the dermoscopic findings observed in two patients suffering from PRP and psoriasis, respectively. The dermoscopic pattern of PRP consisted of round/oval yellowish areas surrounded by vessels of mixed morphology. The latter findings are clearly distinct from the dermoscopic features of psoriasis, which have been extensively investigated previously and are presented also in the psoriatic patient herein. This observation represents an initial indication that dermoscopy could be of value in differentiating between the two entities.
doi:10.3315/jdcr.2013.1131
PMCID: PMC3622511  PMID: 23580911
blood vessels; dermatoscopy; dermoscopy; pityriasis rubra pilaris; psoriasis
14.  “Hardly worth the effort”? Medical journals’ policies and their editors’ and publishers’ views on trial registration and publication bias: quantitative and qualitative study 
Objectives To determine the proportion of medical journals requiring trial registration and to understand their reasons for adopting (or not adopting) such policies and other measures designed to reduce publication bias.
Design Quantitative study of journals’ instructions to authors (in June 2012) and qualitative study of editors’ and publishers’ views on trial registration and publication bias (carried out in Autumn 2012).
Setting Random selection of 200 medical journals publishing clinical trials identified from the Cochrane CENTRAL database.
Participants Editors (n=13) and publishers (n=3) of journals with different policies on trial registration (and with recently changed policies) identified from the survey of their instructions to authors.
Results Only 55/200 journals (28%) required trial registration according to their instructions and a further three (2%) encouraged it. The editors and publishers interviewed explained their journals’ reluctance to require registration in terms of not wanting to lose out to rival journals, not wanting to reject otherwise sound articles or submissions from developing countries, and perceptions that such policies were not relevant to all journals. Some interviewees considered that registration was unnecessary for small or exploratory studies.
Conclusions Although many major medical journals state that they will only publish clinical trials that have been prospectively registered, and such policies have been associated with a dramatic increase in the number of trials being registered, most smaller journals have not adopted such policies. Editors and publishers may be reluctant to require registration because they do not understand its benefits or because they fear that adopting such a policy would put their journal at a disadvantage to competitors.
doi:10.1136/bmj.f5248
PMCID: PMC3805489  PMID: 24014339
15.  PREP-Mt: predictive RNA editor for plant mitochondrial genes 
BMC Bioinformatics  2005;6:96.
Background
In plants, RNA editing is a process that converts specific cytidines to uridines and uridines to cytidines in transcripts from virtually all mitochondrial protein-coding genes. There are thousands of plant mitochondrial genes in the sequence databases, but sites of RNA editing have not been determined for most. Accurate methods of RNA editing site prediction will be important in filling in this information gap and could reduce or even eliminate the need for experimental determination of editing sites for many sequences. Because RNA editing tends to increase protein conservation across species by "correcting" codons that specify unconserved amino acids, this principle can be used to predict editing sites by identifying positions where an RNA editing event would increase the conservation of a protein to homologues from other plants. PREP-Mt takes this approach to predict editing sites for any protein-coding gene in plant mitochondria.
Results
To test the general applicability of the PREP-Mt methodology, RNA editing sites were predicted for 370 full-length or nearly full-length DNA sequences and then compared to the known sites of RNA editing for these sequences. Of 60,263 cytidines in this test set, PREP-Mt correctly classified 58,994 as either an edited or unedited site (accuracy = 97.9%). PREP-Mt properly identified 3,038 of the 3,698 known sites of RNA editing (sensitivity = 82.2%) and 55,956 of the 56,565 known unedited sites (specificity = 98.9%). Accuracy and sensitivity increased to 98.7% and 94.7%, respectively, after excluding the 489 silent editing sites (which have no effect on protein sequence or function) from the test set.
Conclusion
These results indicate that PREP-Mt is effective at identifying C to U RNA editing sites in plant mitochondrial protein-coding genes. Thus, PREP-Mt should be useful in predicting protein sequences for use in molecular, biochemical, and phylogenetic analyses. In addition, PREP-Mt could be used to determine functionality of a mitochondrial gene or to identify particular sequences with unusual editing properties. The PREP-Mt methodology should be applicable to any system where RNA editing increases protein conservation across species.
doi:10.1186/1471-2105-6-96
PMCID: PMC1087475  PMID: 15826309
16.  Representation of authors and editors from countries with different human development indexes in the leading literature on tropical medicine: survey of current evidence 
BMJ : British Medical Journal  2004;328(7450):1229-1232.
Objective To assess the current international representation of members of editorial and advisory boards and authors in the leading peer reviewed literature on tropical medicine.
Design Systematic review.
Main outcome measures Country affiliations, as classified by the human development index, of editorial and advisory board members of all tropical medicine journals referenced by the Institute of Scientific Information (ISI) as of late 2003 and of all contributing authors of full articles published in the six leading journals on tropical medicine in 2000-2.
Results Sixteen (5.1%) of the 315 editorial and advisory board members from the 12 ISI referenced journals on tropical medicine are affiliated to countries with a low human development index and 223 (70.8%) to countries with a high index. Examination of the 2384 full articles published in 2000-2 in the six highest ranking tropical medicine journals showed that 48.1% of contributing authors are affiliated to countries with a high human development index, whereas the percentage of authors from countries with a low index was 13.7%. Articles written exclusively by authors from low ranked countries accounted for 5.0%. Our data indicate that research collaborations between a country with a high human development index and one that has either a medium or a low index are common and account for 26.5% and 16.1% of all full articles, respectively.
Conclusion Current collaborations should be transformed into research partnerships, with the goals of mutual learning and institutional capacity strengthening in the developing world.
doi:10.1136/bmj.38069.518137.F6
PMCID: PMC416596  PMID: 15059851
17.  A Diagram Editor for Efficient Biomedical Knowledge Capture and Integration 
Understanding the molecular mechanisms underlying complex disorders requires the integration of data and knowledge from different sources including free text literature and various biomedical databases. To facilitate this process, we created the Biomedical Concept Diagram Editor (BCDE) to help researchers distill knowledge from data and literature and aid the process of hypothesis development. A key feature of BCDE is the ability to capture information with a simple drag-and-drop. This is a vast improvement over manual methods of knowledge and data recording and greatly increases the efficiency of the biomedical researcher. BCDE also provides a unique concept matching function to enforce consistent terminology, which enables conceptual relationships deposited by different researchers in the BCDE database to be mined and integrated for intelligible and useful results. We hope BCDE will promote the sharing and integration of knowledge from different researchers for effective hypothesis development.
PMCID: PMC3041526  PMID: 21347131
18.  Can a core outcome set improve the quality of systematic reviews? – a survey of the Co-ordinating Editors of Cochrane review groups 
Trials  2013;14:21.
Background
Missing outcome data or the inconsistent reporting of outcome data in clinical research can affect the quality of evidence within a systematic review. A potential solution is an agreed standardized set of outcomes known as a core outcome set (COS) to be measured in all studies for a specific condition. We investigated the amount of missing patient data for primary outcomes in Cochrane systematic reviews, and surveyed the Co-ordinating Editors of Cochrane Review Groups (CRGs) on issues related to the standardization of outcomes in their CRG’s reviews. These groups are responsible for the more than 7,000 protocols and full versions of Cochrane Reviews that are currently available, and the several hundred new reviews published each year, presenting the world’s largest collection of standardized systematic reviews in health care.
Methods
Using an unselected cohort of Cochrane Reviews, we calculated and presented the percentage of missing patient data for the primary outcome measure chosen for each review published by each CRG. We also surveyed the CRG Co-ordinating Editors to see what their policies are with regards to outcome selection and outcomes to include in the Summary of Finding (SoF) tables in their Cochrane Reviews. They were also asked to list the main advantages and challenges of standardizing outcomes across all reviews within their CRG.
Results
In one fifth of the 283 reviews in the sample, more than 50% of the patient data for the primary outcome was missing. Responses to the survey were received from 90% of Co-ordinating Editors. Thirty-six percent of CRGs have a centralized policy regarding which outcomes to include in the SoF table and 73% of Co-ordinating Editors thought that a COS for effectiveness trials should be used routinely for a SoF table.
Conclusions
The reliability of systematic reviews, in particular meta-analyses they contain, can be improved if more attention is paid to missing outcome data. The availability of COSs for specific health conditions might help with this and the concept has support from the majority of Co-ordinating Editors in CRGs.
doi:10.1186/1745-6215-14-21
PMCID: PMC3575292  PMID: 23339751
COMET; Cochrane review groups; Co-ordinating editors; Core outcome set; ORBIT; Systematic reviews; Survey
19.  Conflicts of interest in biomedical publications: considerations for authors, peer reviewers, and editors 
Croatian Medical Journal  2013;54(6):600-608.
This article overviews evidence on common instances of conflict of interest (COI) in research publications from general and specialized fields of biomedicine. Financial COIs are viewed as the most powerful source of bias, which may even distort citation outcomes of sponsored publications. The urge to boost journal citation indicators by stakeholders of science communication is viewed as a new secondary interest, which may compromize the interaction between authors, peer reviewers, and editors. Comprehensive policies on disclosure of financial and non-financial COIs in scholarly journals are presented as proxies of their indexing in evidence-based databases, and examples of successful medical journals are discussed in detail. Reports on clinical trials, systematic reviews, meta-analyses, and clinical practice guidelines may be unduly influenced by author-pharmaceutical industry relations, but these publications do not always contain explicit disclosures to allow the readers to judge the reliability of the published conclusions and practice-changing recommendations. The article emphasizes the importance of adhering to the guidance on COI from learned associations such as the International Committee of Medical Journal Editors (ICMJE). It also considers joint efforts of authors, peer reviewers, and editors as a foundation for appropriately defining and disclosing potential COIs.
doi:10.3325/cmj.2013.54.600
PMCID: PMC3893982  PMID: 24382859
20.  FORG3D: Force-directed 3D graph editor for visualization of integrated genome scale data 
BMC Systems Biology  2009;3:26.
Background
Genomics research produces vast amounts of experimental data that needs to be integrated in order to understand, model, and interpret the underlying biological phenomena. Interpreting these large and complex data sets is challenging and different visualization methods are needed to help produce knowledge from the data.
Results
To help researchers to visualize and interpret integrated genomics data, we present a novel visualization method and bioinformatics software tool called FORG3D that is based on real-time three-dimensional force-directed graphs. FORG3D can be used to visualize integrated networks of genome scale data such as interactions between genes or gene products, signaling transduction, metabolic pathways, functional interactions and evolutionary relationships. Furthermore, we demonstrate its utility by exploring gene network relationships using integrated data sets from a Caenorhabditis elegans Parkinson's disease model.
Conclusion
We have created an open source software tool called FORG3D that can be used for visualizing and exploring integrated genome scale data.
doi:10.1186/1752-0509-3-26
PMCID: PMC2651117  PMID: 19239683
21.  Jalview Version 2—a multiple sequence alignment editor and analysis workbench 
Bioinformatics  2009;25(9):1189-1191.
Summary: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server.
Availability: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org
Contact: g.j.barton@dundee.ac.uk
doi:10.1093/bioinformatics/btp033
PMCID: PMC2672624  PMID: 19151095
22.  Do Author-Suggested Reviewers Rate Submissions More Favorably than Editor-Suggested Reviewers? A Study on Atmospheric Chemistry and Physics 
PLoS ONE  2010;5(10):e13345.
Background
Ratings in journal peer review can be affected by sources of bias. The bias variable investigated here was the information on whether authors had suggested a possible reviewer for their manuscript, and whether the editor had taken up that suggestion or had chosen a reviewer that had not been suggested by the authors. Studies have shown that author-suggested reviewers rate manuscripts more favorably than editor-suggested reviewers do.
Methodology/Principal Findings
Reviewers' ratings on three evaluation criteria and the reviewers' final publication recommendations were available for 552 manuscripts (in total 1145 reviews) that were submitted to Atmospheric Chemistry and Physics, an interactive open access journal using public peer review (authors' and reviewers' comments are publicly exchanged). Public peer review is supposed to bring a new openness to the reviewing process that will enhance its objectivity. In the statistical analysis the quality of a manuscript was controlled for to prevent favorable reviewers' ratings from being attributable to quality instead of to the bias variable.
Conclusions/Significance
Our results agree with those from other studies that editor-suggested reviewers rated manuscripts between 30% and 42% less favorably than author-suggested reviewers. Against this backdrop journal editors should consider either doing without the use of author-suggested reviewers or, if they are used, bringing in more than one editor-suggested reviewer for the review process (so that the review by author-suggested reviewers can be put in perspective).
doi:10.1371/journal.pone.0013345
PMCID: PMC2954795  PMID: 20976226
23.  DeviceEditor visual biological CAD canvas 
Background
Biological Computer Aided Design (bioCAD) assists the de novo design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.
Results
We report the development and deployment of web-based bioCAD software, DeviceEditor, which provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. We demonstrate how biological designs are rendered on the DeviceEditor canvas, and we present effective visualizations of genetic component ordering and combinatorial variations within complex designs.
Conclusions
DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs.
doi:10.1186/1754-1611-6-1
PMCID: PMC3317443  PMID: 22373390
bioCAD; Visual design abstraction; Correct-by-construction design; Design specification rules; Combinatorial library; DNA assembly
24.  Effect of editors’ implementation of CONSORT guidelines on the reporting of abstracts in high impact medical journals: interrupted time series analysis  
Objective To investigate the effect of the CONSORT for Abstracts guidelines, and different editorial policies used by five leading general medical journals to implement the guidelines, on the reporting quality of abstracts of randomised trials.
Design Interrupted time series analysis.
Sample We randomly selected up to 60 primary reports of randomised trials per journal per year from five high impact, general medical journals in 2006-09, if indexed in PubMed with an electronic abstract. We excluded reports that did not include an electronic abstract, and any secondary trial publications or economic analyses. We classified journals in three categories: those not mentioning the guidelines in their instructions to authors (JAMA and New England Journal of Medicine), those referring to the guidelines in their instructions to authors but with no specific policy to implement them (BMJ), and those referring to the guidelines in their instructions to authors with an active policy to implement them (Annals of Internal Medicine and Lancet). Two authors extracted data independently using the CONSORT for Abstracts checklist.
Main outcome Mean number of CONSORT items reported in selected abstracts, among nine items reported in fewer than 50% of the abstracts published across the five journals in 2006.
Results We assessed 955 reports of abstracts of randomised trials. Journals with an active policy to enforce the guidelines showed an immediate increase in the level of mean number of items reported (increase of 1.50 items; P=0.0037). At 23 months after publication of the guidelines, the mean number of items reported per abstract for the primary outcome was 5.41 of nine items, a 53% increase compared with the expected level estimated on the basis of pre-intervention trends. The change in level or trend did not increase in journals with no policy to enforce the guidelines (BMJ, JAMA, and New England Journal of Medicine).
Conclusion Active implementation of the CONSORT for Abstracts guidelines by journals can lead to improvements in the reporting of abstracts of randomised trials.
doi:10.1136/bmj.e4178
PMCID: PMC3382226  PMID: 22730543
25.  Letter to the Editor: On the stability and ranking of predictors from random forest variable importance measures 
Briefings in Bioinformatics  2011;12(4):369-373.
A recent study examined the stability of rankings from random forests using two variable importance measures (mean decrease accuracy (MDA) and mean decrease Gini (MDG)) and concluded that rankings based on the MDG were more robust than MDA. However, studies examining data-specific characteristics on ranking stability have been few. Rankings based on the MDG measure showed sensitivity to within-predictor correlation and differences in category frequencies, even when the number of categories was held constant, and thus may produce spurious results. The MDA measure was robust to these data characteristics. Further, under strong within-predictor correlation, MDG rankings were less stable than those using MDA.
doi:10.1093/bib/bbr016
PMCID: PMC3137934  PMID: 21498552
Random forest; variable importance measures; stability; ranking; correlation; linkage disequilibrium

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