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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2017

Wikipedia as a gateway to biomedical research: The relative distribution and use of citations in the English Wikipedia

Wikipedia is a gateway to knowledge. However, the extent to which this gateway ends at Wikipedia or continues via supporting citations is unknown. Wikipedias gateway functionality has implications for information design and education, notably in medicine. This study aims to establish benchmarks for the relative distribution and referral (click) rate of citations--as indicated by presence of a Digital Object Identifier (DOI)--from Wikipedia, with a focus on medical citations.\n\nDOIs referred from the English Wikipedia in August 2016 were obtained from Crossref.org. Next, based on a DOIs presence on a WikiProject Medicine page, all DOIs in Wikipedia were categorized as medical (WP:MED) or non-medical (non-WP:MED). Using this categorization, referred DOIs were classified as WP:MED, non-WP:MED, or BOTH, meaning the DOI may have been referred from either category. Data were analyzed using descriptive and inferential statistics.\n\nOut of 5.2 million Wikipedia pages, 4.42% (n=229,857) included at least one DOI. 68,870 were identified as WP:MED, with 22.14% (n=15,250) featuring one or more DOIs. WP:MED pages featured on average 8.88 DOI citations per page, whereas non-WP:MED pages had on average 4.28 DOI citations. For DOIs only on WP:MED pages, a DOI was referred every 2,283 pageviews and for non-WP-MED pages every 2,467 pageviews. DOIs from BOTH pages accounted for 12% (n=58,475) of referrals, making determining a referral rate for BOTH impossible.\n\nWhile these results cannot provide evidence of greater citation referral from WP:MED than non-WP:MED, they do provide benchmarks to assess strategies for changing referral patterns. These changes might include editors adopting new methods for designing and presenting citations or the introduction of teaching strategies that address the value of consulting citations as a tool for extending learning.

scientific communication and education↗

bioRxiv2014

How many digits in a mean are worth reporting?

Most bioscientists need to report mean values, yet many have little idea of how many digits are significant, and at what point further digits are mere random junk. Thus a recent report that the mean of 17 values was 3.863 with a standard error of the mean (SEM) of 2.162 revealed only that none of the seven authors understood the limitations of their work. The simple rule derived here by experiment for restricting a mean value to its significant digits (sig-digs) is this: the last sig-dig in the mean value is at the same decimal decade as the first sig-dig (the first non-zero) in the SEM. An extended rule for the mean, and a different rule for the SEM itself are also derived. For the example above the reported values should be a mean of 4 with SEM 2.2. Routine application of these simple rules will often show that a result is not as compelling as one had hoped.

Scientific Communication and Education↗

bioRxiv2014

A plea for evidence in ecosystem service science: a framework and its application

The ecosystem service concept is at the interface of ecology, economics and politcs, with scientific results rapidly translated into management or political action. This emphasises the importance of reliable recommendations provided by scientist. We propose to use evidence-based practice in ecosystem service science in order to evaluate and improve the reliability of scientific statements. For this purpose, we introduce a level-of-evidence scale ranking study designs (e.g. review, case-control, descriptive) in combination with a study quality checklist. For illustration, the concept was directly applied to 12 case studies. We also review criticisms levered against evidence-based practice and how it applies to ecosystem services science. We further discuss who should use the evidence-based concept and suggest important next steps, with a focus on the development of guidelines for methods used in ecosystem service assessments.

Scientific Communication and Education↗

bioRxiv2014

Characterization of the Peer Review Network at the Center for Scientific Review, National Institutes of Health

The National Institutes of Health (NIH) is the largest source of funding for biomedical research in the world. This funding is largely effected through a competitive grants process. Each year the Center for Scientific Review (CSR) at NIH manages the evaluation, by peer review, of more than 55,000 grant applications. A relevant management question is how this scientific evaluation system, supported by finite resources, could be continuously evaluated and improved for maximal benefit to the scientific community and the taxpaying public. Towards this purpose, we have created the first system-level description of peer review at CSR by applying text analysis, bibliometric, and graph visualization techniques to administrative records. We identify otherwise latent relationships across scientific clusters, which in turn suggest opportunities for structural reorganization of the system based on expert evaluation. Such studies support the creation of monitoring tools and provide transparency and knowledge to stakeholders.

Scientific Communication and Education↗

bioRxiv2014

An evidence assessment tool for ecosystem services and conservation studies

Reliability of scientific findings is always important, but even more so in ecosystem service science, where results can directly lead to policy implementations. The assessment of reliability resulted in the introduction of the evidence-based concept in the medical sciences. It aims at identifying the best available information to answer the question of interest. In environmental sciences, the evidence-based concept is well developed [very few people actually use it!] in conservation, but so far no guidelines exists for ecosystem services science. To apply the evidence-based concept in practice we need a scale to rank study designs commonly used in ecosystem services science as well as an assessment of the actual quality of implementation in a specific study. Here, we define a framework for evidence-based ecosystem service science, together with a design scale and a critical-appraisal checklist. The approach is described with detailed examples and specific suggestions for different user groups.

Scientific Communication and Education↗

bioRxiv2014

From peer-reviewed to peer-reproduced: a role for data standards, models and computational workflows in scholarly publishing

MotivationReproducing the results from a scientific paper can be challenging due to the absence of data and the computational tools required for their analysis. In addition, details relating to the procedures used to obtain the published results can be difficult to discern due to the use of natural language when reporting how experiments have been performed. The Investigation/Study/Assay (ISA), Nanopublications (NP) and Research Objects (RO) models are conceptual data modelling frameworks that can structure such information from scientific papers. Computational workflow platforms can also be used to reproduce analyses of data in a principled manner. We assessed the extent by which ISA, NP and RO models, together with the Galaxy workflow system, can capture the experimental processes and reproduce the findings of a previously published paper reporting on the development of SOAPdenovo2, a de novo genome assembler.\n\nResultsExecutable workflows were developed using Galaxy which reproduced results that were consistent with the published findings. A structured representation of the information in the SOAPdenovo2 paper was produced by combining the use of ISA, NP and RO models. By structuring the information in the published paper using these data and scientific workflow modelling frameworks, it was possible to explicitly declare elements of experimental design, variables and findings. The models served as guides in the curation of scientific information and this led to the identification of inconsistencies in the original published paper, thereby allowing its authors to publish corrections in the form of an errata.\n\nAvailabilitySOAPdenovo2 scripts, data and results are available through the GigaScience Database: http://dx.doi.org/10.5524/100044; the workflows are available from GigaGalaxy: http://galaxy.cbiit.cuhk.edu.hk; and the representations using the ISA, NP and RO models are available through the SOAPdenovo2 case study website http://isa-tools.github.io/soapdenovo2/. Contact: philippe.rocca-serra@oerc.ox.ac.uk and susanna.assunta-sansone@oerc.ox.ac.uk

Scientific Communication and Education↗

bioRxiv2015

Association of TSH level above 2.1 mlU/L and first trimester pregnancy loss in anti-TPO antibody negative women

Although the exact level of TSH that is indicative of risk of pregnancy loss is not known, a number of studies have suggested a range of values for TSH level that are associated with first trimester pregnancy loss. We conducted an unmatched case-control study to test if a TSH level above 2.1 mlU/L is associated with first trimester pregnancy loss in anti-TPO antibody negative women. We found relatively higher number of women in the case group (18) whose TSH level was above 2.1 mlU/L compared to 7 women in control group. When considered patients in Group I (TSH [≤] 2.1 mlU/L), 45.74% had miscarriage while 54.26% did not have miscarriage within first trimester of pregnancy. Among the Group II patients (TSH > 2.1 mlU/L), 78% had miscarriage and 28% did not have miscarriage. Noticeably there is a larger proportion of miscarriage among the women with TSH level above 2.1 mlU/L. The association between TSH level and first trimester pregnancy loss was statistically significant (p=.0196). From the multivariate analysis, odds ratio for TSH level (OR 4.0, 95% CI: 1.44-11.16) indicates that odds of having miscarriage whose TSH level is above 2.1 mlU/L is 4 times compared to those with TSH level below 2.1 mlU/L after adjusting for the effects of age and BMI. At a global level, the findings of this study provide evidence to the existing discussion on redefining the upper limit of TSH level that is related to first trimester pregnancy loss. At the local level, the results will have direct implication in facilitating management of future pregnancies particularly during the first trimester among Bangladeshi thyroid autoantibody negative women. (268 words)

Scientific Communication and Education↗

bioRxiv2015

Why clinical trials are terminated

BackgroundEvidence-based clinical practice relies on unbiased reporting of negative results. Meta-analysis of drug safety and efficacy across many clinical trials is difficult given the unconstrained nature of reasons that are provided to ClinicalTrials.gov to explain clinical trial terminations.\n\nMethods and FindingsWe scanned all trials in ClinicalTrials.gov marked with the \"terminated\" status (N=3122), meaning the trial had been stopped before the scheduled end date. Under the current reporting framework, any number of reasons may be given for termination, and these need not conform to a controlled vocabulary. Here we develop a controlled vocabulary for trial termination, and map each terminated trial to as many as three vocabulary terms. Mapping to this \"ontology of termination\" allows further analysis and conclusions. First, we identify the subset of terminated trials that ended citing safety concerns (6.2%) or failure to establish efficacy (10.8%), and were further able to stratify these rates across trials of different phases. Second, we examine termination reasons where a stricter data model could have preserved more evidentiary value, either because the data model was misused (7.6%) or because the given reason left unclear whether the decision to terminate was based on analysis of the data (74.9%, with 20.4% mentioning a decision-maker that may have had access to the data). Third, we show that imposing a controlled vocabulary of reasons for termination would avoid ambiguity and improve the evidentiary value of clinical trials.\n\nConclusionsWe encourage wider use of an \"ontology of termination\" and propose four questions that should be posed on trial termination. These simple steps would promote transparency and enable ready access to negative trial results for meta-analysis.

Scientific Communication and Education↗

bioRxiv2015

Publishing descriptions of non-public clinical datasets: guidance for researchers, repositories, editors and funding organisations

Sharing of experimental clinical research data usually happens between individuals or research groups rather than via public repositories, in part due to the need to protect research participant privacy. This approach to data sharing makes it difficult to connect journal articles with their underlying datasets and is often insufficient for ensuring access to data in the long term. Voluntary data sharing services such as the Yale Open Data Access (YODA) and Clinical Study Data Request (CSDR) projects have increased accessibility to clinical datasets for secondary uses while protecting patient privacy and the legitimacy of secondary analyses but these resources are generally disconnected from journal articles - where researchers typically search for reliable information to inform future research. New scholarly journal and article types dedicated to increasing accessibility of research data have emerged in recent years and, in general, journals are developing stronger links with data repositories. There is a need for increased collaboration between journals, data repositories, researchers, funders, and voluntary data sharing services to increase the visibility and reliability of clinical research. We propose changes to the format and peer-review process for journal articles to more robustly link them to data that are only available on request. We also propose additional features for data repositories to better accommodate non-public clinical datasets, including Data Use Agreements (DUAs).

Scientific Communication and Education↗

bioRxiv2015

Accelerating Scientific Publication in Biology

Scientific publications enable results and ideas to be transmitted throughout the scientific community. The number and type of journal publications also have become the primary criteria used in evaluating career advancement. Our analysis suggests that publication practices have changed considerably in the life sciences over the past thirty years. Considerably more experimental data is now required for publication, and the average time required for graduate students to publish their first paper has increased and is approaching the desirable duration of Ph.D. training. Since publication is generally a requirement for career progression, schemes to reduce the time of graduate student and postdoctoral training may be difficult to implement without also considering new mechanisms for accelerating communication of their work. The increasing time to publication also delays potential catalytic effects that ensue when many scientists have access to new information. The time has come for the life scientists, funding agencies, and publishers to discuss how to communicate new findings in a way that best serves the interests of the public and scientific community.

Scientific Communication and Education↗

bioRxiv2015

Classifying Aging as a Disease in the context of ICD-11

Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organizations 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease.

Scientific Communication and Education↗

bioRxiv2015

Relative Citation Ratio (RCR): A new metric that uses citation rates to measure influence at the article level

Despite their recognized limitations, bibliometric assessments of scientific productivity have been widely adopted. We describe here an improved method that makes novel use of the co-citation network of each article to field-normalize the number of citations it has received. The resulting Relative Citation Ratio is article-level and field-independent, and provides an alternative to the invalid practice of using Journal Impact Factors to identify influential papers. To illustrate one application of our method, we analyzed 88,835 articles published between 2003 and 2010, and found that the National Institutes of Health awardees who authored those papers occupy relatively stable positions of influence across all disciplines. We demonstrate that the values generated by this method strongly correlate with the opinions of subject matter experts in biomedical research, and suggest that the same approach should be generally applicable to articles published in all areas of science. A beta version of iCite, our web tool for calculating Relative Citation Ratios of articles listed in PubMed, is available at https://icite.od.nih.gov.

Scientific Communication and Education↗

bioRxiv2015

Evolving cohesion metrics of a research network on rare diseases: a longitudinal study over 14 years

Research collaboration is necessary, rewarding, and beneficial. Cohesion between team members is related to their collective efficiency. To assess collaboration processes and their eventual outcomes, agencies need innovative methods - and social network approaches are emerging as a useful analytical tool. We identified the research output and citation data of a network of 61 research groups formally engaged in publishing rare disease research between 2000 and 2013. We drew the collaboration networks for each year and computed the global and local measures throughout the period, relating connectivity with the normalized impact. Although global network measures remained steady over the whole period, the local and subgroup metrics revealed a growing cohesion between the teams. Transitivity and density showed little or no variation throughout the period. In contrast the following points indicated an evolution towards greater network cohesion: the emergence of a giant component (which grew from just 30% to reach 85% of groups); the decreasing number of communities (following a tripling in the average number of members); the growing number of fully connected subgroups; and increasing average strength. Normalized citation measures, although ranking the member groups as above average impact for Spanish biomedical output, do not support correlation between collaboration and citation impact. The Spanish research network on rare diseases has evolved towards a growing cohesion - as revealed by local and subgroup metrics following social network analysis. This greater cohesion does not translate into a greater impact, as measured by the citation analysis of the papers.

Scientific Communication and Education↗

bioRxiv2015

Sequential Multiple Assignment Randomized Trials: An Opportunity for Improved Design of Stroke Reperfusion Trials

Background: Modern clinical trials in stroke reperfusion fall into two categories: alternative systemic pharmacological regimens to alteplase and \"rescue\" endovascular approaches using targeted thrombectomy devices and/or medications delivered directly for persistently vessel occlusions. Clinical trials in stroke have not evaluated how initial pharmacological thrombolytic management might influence subsequent rescue strategy. A sequential multiple assignment randomized trial (SMART) is a novel trial design that can test these dynamic treatment regimens and lead to treatment guidelines which more closely mimic practice.\n\nAim: To characterize a SMART design in comparison to traditional approaches for stroke reperfusion trials.\n\nMethods: We conducted a numerical simulation study that evaluated the performance of contrasting acute stroke clinical trial designs of both initial reperfusion and rescue therapy. We compare a SMART design where the same patients are followed through initial reperfusion and rescue therapy within one trial to a standard phase III design comparing two reperfusion treatments and a separate phase II futility design of rescue therapy in terms of sample size, power, and ability to address particular research questions.\n\nResults: Traditional trial designs can be well powered and have optimal design characteristics for independent treatment effects. When treatments, such as the reperfusion and rescue therapies, may interact, commonly used designs fail to detect this. A SMART design, with similar sample size to standard designs, can detect treatment interactions.\n\nConclusions: The use of SMART designs to investigate effective and realistic dynamic treatment regimens is a promising way to accelerate the discovery of new, effective treatments for stroke.

Scientific Communication and Education↗

bioRxiv2016

Comparing the Citation Performance of PNAS Papers by Submission Track

Purpose: To determine whether papers contributed by National Academy of Sciences (NAS) members perform differently than direct submissions.\n\nData/Methods: 55,889 original papers published in PNAS from 1997 through 2014. Regression analysis measuring total citations, controlling for editorial track (Contributed, Direct, Communicated), date of publication, and paper topic.\n\nMain findings: Contributed papers consistently underperformed against Direct submissions, receiving 9% fewer citations, ceteris paribus. The effect was greatest for Social Sciences papers (12% fewer citations). Nonetheless, the main effect has attenuated over the past decade, from 13.6% fewer citations in 2005 to just 2.2% fewer citations in 2014.\n\nSignificance: Successive editorial policies placing limits, restrictions, and other qualifications on the publication privileges of NAS members may be responsible for the submission of better performing Contributed papers.

Scientific Communication and Education↗

bioRxiv2016

Two Similarity Metrics for Medical Subject Headings (MeSH): An Aid to Biomedical Text Mining and Author Name Disambiguation

In the present paper, we have created and characterized several similarity metrics for relating any two Medical Subject Headings (MeSH terms) to each other. The article-based metric measures the tendency of two MeSH terms to appear in the MEDLINE record of the same article. The author-based metric measures the tendency of two MeSH terms to appear in the body of articles written by the same individual (using the 2009 Author-ity author name disambiguation dataset as a gold standard). The two metrics are only modestly correlated with each other (r = 0.50), indicating that they capture different aspects of term usage. The article-based metric provides a measure of semantic relatedness, and MeSH term pairs that co-occur more often than expected by chance may reflect relations between the two terms. In contrast, the author metric is indicative of how individuals practice science, and may have value for author name disambiguation and studies of scientific discovery. We have calculated article metrics for all MeSH terms appearing in at least 25 articles in MEDLINE (as of 2014) and author metrics for MeSH terms published as of 2009. The dataset is freely available for download and can be queried at http://arrowsmith.psych.uic.edu/arrowsmith_uic/mesh_pair_metrics.html.

Scientific Communication and Education↗

bioRxiv2016

Evaluation of Techniques for Performing Cellular Isolation and Preservation during Microgravity Conditions

Genomic and epigenomic studies require the precise transfer of small volumes from one container to another. Epigenomic and transcriptional analysis require separation of purified cell types, and long term preservation of cells requires their isolation and transfer into appropriate freezing media. There are currently no protocols for these procedures on the ISS. Currently samples are either frozen as mixed cell populations, with poor yield, or returned under ambient conditions, requiring timing with Soyuz missions. Here, we evaluate the feasibility of translating terrestrial cell purification techniques to the ISS. Our evaluations were performed in microgravity conditions during parabolic atmospheric flight. The pipetting of open liquids in microgravity was evaluated using analog blood fluids and several types of pipette hardware. The best performing pipettes were used to evaluate the pipetting steps required for peripheral blood mononuclear cell (PBMC) isolation via density gradient centrifugation (DGC). Evaluation of actual blood products was performed for both the overlay of diluted blood, and the extraction of isolated PBMCs. We also validated magnetic purification of cells. We found that positive displacement pipettes avoided air bubbles, and the tips allowed the strong surface tension of water, glycerol and blood to maintain a patent meniscus and withstand robust pipetting in microgravity. These procedures will greatly increase the breadth of research that can be performed onboard the ISS, and allow improvised experimentation on extraterrestrial missions.

Scientific Communication and Education↗

bioRxiv2016

Advancing insect vector biology research: a community survey for future directions, research applications and infrastructure requirements

BackgroundVector-borne pathogens impact public health and economies worldwide. It has long been recognized that research on arthropod vectors such as mosquitoes, ticks, sandflies and midges which transmit parasites and arboviruses to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is an increasing issue. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies. This has increased interest in vector biology and genetics as well as vector-pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructures will benefit from community input.\n\nMethodology/Principal FindingsA survey initiated by the European Horizon2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key issues that should be addressed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such work to be carried out.\n\nConclusions/SignificanceWe summarize the key findings of the survey which in particular reflect priorities in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations.\n\nAuthor SummaryResearch on arthropod vectors that transmit so-called arboviruses or parasites, such as mosquitoes, ticks, sandflies and midges is important for the development of control measures that target transmission of these pathogens. Important developments in this research area, for example vector genome sequencing, genome manipulation and use of transmission-blocking endosymbionts such as Wolbachia have increased interest in vector biology. As such, strategic decisions on research directions as well as research infrastructures will benefit from community input. A survey initiated by the European Horizon2020 INFRAVEC-2 consortium set out to investigate priorities in the vector biology research community as well as key issues that impact on research, and access to the structures and services that allow such studies to be carried out. Here we summarize the key findings of this survey, which in particular reflect priorities in European countries. The survey data will be of use to decision makers such as governments and research organizations, but also researchers and others in the field.

Scientific Communication and Education↗