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Concept: Medical research

392

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Concepts: Medicine, Model organism, Animal testing, Drug discovery, Model, Medical research, Orphan drug

215

As social scientists have investigated the political and social factors influencing public opinion in science-related policy debates, there has been growing interest in the implications of this research for public communication and outreach. Given the level of political polarization in the United States, much of the focus has been on partisan differences in public opinion, the strategies employed by political leaders and advocates that promote those differences, and the counter-strategies for overcoming them. Yet this focus on partisan differences tends to overlook the processes by which core beliefs about science and society impact public opinion and how these schema are often activated by specific frames of reference embedded in media coverage and popular discourse. In this study, analyzing cross-sectional, nationally representative survey data collected between 2002 and 2010, we investigate the relative influence of political partisanship and science-related schema on Americans' support for embryonic stem cell research. In comparison to the influence of partisan identity, our findings suggest that generalized beliefs about science and society were more chronically accessible, less volatile in relation to media attention and focusing events, and an overall stronger influence on public opinion. Classifying respondents into four unique audience groups based on their beliefs about science and society, we additionally find that individuals within each of these groups split relatively evenly by partisanship but differ on other important dimensions. The implications for public engagement and future research on controversies related to biomedical science are discussed.

Concepts: Stem cell, Sociology, Science, Embryonic stem cell, Medical research, Social sciences, Political philosophy, Society

185

Next-generation sequencing (NGS) is increasingly being adopted as the backbone of biomedical research. With the commercialization of various affordable desktop sequencers, NGS will be reached by increasing numbers of cellular and molecular biologists, necessitating community consensus on bioinformatics protocols to tackle the exponential increase in quantity of sequence data. The current resources for NGS informatics are extremely fragmented. Finding a centralized synthesis is difficult. A multitude of tools exist for NGS data analysis; however, none of these satisfies all possible uses and needs. This gap in functionality could be filled by integrating different methods in customized pipelines, an approach helped by the open-source nature of many NGS programmes. Drawing from community spirit and with the use of the Wikipedia framework, we have initiated a collaborative NGS resource: The NGS WikiBook. We have collected a sufficient amount of text to incentivize a broader community to contribute to it. Users can search, browse, edit and create new content, so as to facilitate self-learning and feedback to the community. The overall structure and style for this dynamic material is designed for the bench biologists and non-bioinformaticians. The flexibility of online material allows the readers to ignore details in a first read, yet have immediate access to the information they need. Each chapter comes with practical exercises so readers may familiarize themselves with each step. The NGS WikiBook aims to create a collective laboratory book and protocol that explains the key concepts and describes best practices in this fast-evolving field.

Concepts: Molecular biology, Biology, Sequence, Medical research, Sustainability, Bench, Exponential growth, Wikipedia

174

BACKGROUND: MEDLINE®/PubMed® indexes over 20 million biomedical articles, providing curated annotation of contents using a controlled vocabulary known as Medical Subject Headings (MeSH). The MeSH vocabulary, developed over 50+ years, provides a broad coverage of topics across biomedical research. Distilling the essential biomedical themes for a topic of interest from the relevant literature is important to both understand the importance of related concepts and discover new relationships. RESULTS: We introduce a novel method for determining enriched curator-assigned MeSH annotations in a set of papers associated to a topic, such as a gene, an author or a disease. We generate MeSH Over-representation Profiles (MeSHOPs) to quantitatively summarize the annotations in a form convenient for further computational analysis and visualization. Based on a hyper geometric distribution of assigned terms, MeSHOPs statistically account for the prevalence of the associated biomedical annotation while highlighting unusually prevalent terms based on a specified background. MeSHOPs can be visualized using word clouds, providing a succinct quantitative graphical representation of the relative importance of terms. Using the publication dates of articles, MeSHOPs track changing patterns of annotation over time. Since MeSHOPs are quantitative vectors, MeSHOPs can be compared using standard techniques such as hierarchical clustering. The reliability of MeSHOP annotations is assessed based on the capacity to re-derive the subset of the Gene Ontology annotations with equivalent MeSH terms. CONCLUSIONS: MeSHOPs allows quantitative measurement of the degree of association between any entity and the annotated medical concepts, based directly on relevant primary literature. Comparison of MeSHOPs allows entities to be related based on shared medical themes in their literature. A web interface is provided for generating and visualizing MeSHOPs.

Concepts: Bioinformatics, Controlled vocabulary, Medical research, Mesh, Medical Subject Headings, GoPubMed

105

Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too.

Concepts: Endocrinology, Medical research, Orphan drug

84

The National Institutes of Health needs to make radical changes to ensure that biomedical research continues to thrive in the United States.

Concepts: United States, Poverty in the United States, U.S. state, Medical research, National Institutes of Health, Massachusetts, Radical Republicans, Health sciences

66

The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession-and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches. Instead, it is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research ecosystem.

Concepts: Time, Medical research, Biomedical scientist

58

Systematic reviews (SRs) can help decision makers interpret the deluge of published biomedical literature. However, a SR may be of limited use if the methods used to conduct the SR are flawed, and reporting of the SR is incomplete. To our knowledge, since 2004 there has been no cross-sectional study of the prevalence, focus, and completeness of reporting of SRs across different specialties. Therefore, the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs.

Concepts: Epidemiology, Disease, Randomized controlled trial, Medical research, Health sciences

57

The US research enterprise is under significant strain due to stagnant funding, an expanding workforce, and complex regulations that increase costs and slow the pace of research. In response, a number of groups have analyzed the problems and offered recommendations for resolving these issues. However, many of these recommendations lacked follow-up implementation, allowing the damage of stagnant funding and outdated policies to persist. Here, we analyze nine reports published since the beginning of 2012 and consolidate over 250 suggestions into eight consensus recommendations made by the majority of the reports. We then propose how to implement these consensus recommendations, and we identify critical issues, such as improving workforce diversity and stakeholder interactions, on which the community has yet to achieve consensus.

Concepts: Medical research, Policy, Implementation, Design, The Damage

47

A cross-campus, cross-career stage and cross-disciplinary series of discussions at a large public university has produced a series of recommendations for addressing the problems confronting the biomedical research community in the US.

Concepts: Medical research