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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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Zika Virus Disease: A Simple Model Approach to Rapid Impact Assessment

There has been substantial media attention regarding Zika infection as a threat to pregnancy, prompted by WHOs declaration of a Public Health Event of International Concern (PHEIC). Here we present a simple risk assessment model for two states within the continental United States at-risk for autochthonous transmission of Zika virus, Texas and Florida. Our simple impact assessment model is partially validating at this early interval in the crisis.

Scientific Communication and Education

Has the time come for preprints in biology?

Preprints, non-peer reviewed drafts of manuscripts available on the internet, have been used in conjunction with peer review and publication in journals in the physical sciences for almost 25 years. Recently, more scientists have been discussing whether preprints can play a similar role in biological and biomedical research. Here, I discuss my excitement and concerns about the role that preprints can play in disseminating research findings in the life sciences.

Scientific Communication and Education

Discrimination between Onchocerca volvulus and O. ochengi filarial larvae in Simulium damnosum (s.l.) and their distribution throughout central Ghana using a versatile high-resolution speciation assay

BackgroundGenetic surveillance of the human filarial parasite, Onchocerca volvulus, from onchocerciasis endemic regions will ideally focus on genotyping individual infective larval stages collected from their intermediate host, Simuliid blackflies. However, blackflies also transmit other Onchocerca species, including the cattle parasite O. ochengi, which are difficult to distinguish from the human parasite based on morphological characteristics alone. This study describes a versatile approach to discriminate between O. volvulus and O. ochengi that is demonstrated using parasite infective larvae dissected from blackflies.\n\nResultsA speciation assay was designed based on genetic differentiation between O. volvulus and O. ochengi mitochondrial genome sequences that can be performed in highthroughput high-resolution melt (HRM)- or lower throughput conventional restriction fragment length polymorphism (RFLP) analyses. This assay was validated on 185 Onchocerca larvae dissected from blackflies captured from 14 communities in Ghana throughout 2011-13. The frequency of O. ochengi was approximately 67 % of all larvae analysed, which is significantly higher than previously reported in this region. Furthermore, the species distribution was not uniform throughout the study region, with 25 %, 47 % and 93 % of O. volvulus being found in the western-most (Black Volta, Tain and Tombe), the central (Pru) and eastern-most (Daka) river basins, respectively.\n\nConclusionsThis tool provides a simple and cost-effective approach to determine the identity and distribution of two Onchocerca species, and will be valuable for future genetic studies that focus on parasites collected from blackflies. The results presented highlight the need to discriminate Onchocerca species in transmission studies, as the frequency of each species varied significantly between the communities studied.

Scientific Communication and Education

The Prevalence of Inappropriate Image Duplication in Biomedical Research Publications

Inaccurate data in scientific papers can result from honest error or intentional falsification. This study attempted to determine the percentage of published papers containing inappropriate image duplication, a specific type of inaccurate data. The images from a total of 20,621 papers in 40 scientific journals from 1995-2014 were visually screened. Overall, 3.8% of published papers contained problematic figures, with at least half exhibiting features suggestive of deliberate manipulation. The prevalence of papers with problematic images rose markedly during the past decade. Additional papers written by authors of papers with problematic images had an increased likelihood of containing problematic images as well. As this analysis focused only on one type of data, it is likely that the actual prevalence of inaccurate data in the published literature is higher. The marked variation in the frequency of problematic images among journals suggest that journal practices, such as pre-publication image screening, influence the quality of the scientific literature.

Scientific Communication and Education

Is most published research really false?

There has been an increasing concern that most published medical findings are false. But what does it mean to be false? Here we describe the range of definitions of false discoveries in the scientific literature. We summarize the philosophical, statistical, and experimental evidence for each type of false discovery. We discuss common underpinning problems with the scientific and data analytic practices and point to tools and behaviors that can be implemented to reduce the problems with published scientific results.

Scientific Communication and Education

search.bioPreprint: a discovery tool for cutting edge, preprint biomedical research articles

The time it takes for a completed manuscript to be published traditionally can be extremely lengthy. Article publication delay, which occurs in part due to constraints associated with peer review, can prevent the timely dissemination of critical and actionable data associated with new information on rare diseases or developing health concerns such as Zika virus. Preprint servers are open access online repositories housing preprint research articles that enable authors (1) to make their research immediately and freely available and (2) to receive commentary and peer review prior to journal submission. There is a growing movement of preprint advocates aiming to change the current journal publication and peer review system, proposing that preprints catalyze biomedical discovery, support career advancement, and improve scientific communication. While the number of articles submitted to and hosted by preprint servers are gradually increasing, there has been no simple way to identify biomedical research published in a preprint format, as they are not typically indexed and are only discoverable by directly searching the specific preprint server websites. To address this issue, we created a search engine that quickly compiles preprints from disparate host repositories and provides a one-stop search solution. Additionally, we developed a web application that bolsters the discovery of preprints by enabling each and every word or phrase appearing on any website to be integrated with articles from preprint servers. The bioPreprint search engine is publicly available at http://www.hsls.pitt.edu/resources/preprint.

Scientific Communication and Education

Building a Web of Linked Data Resources to Advance Neuroscience Research

The fundamental goal of neuroscience is to understand the nervous system at all levels of description, from molecular components to behavior. The complexity of achieving this goal in neuroscience, and biomedicine in general, poses many technical and sociological challenges. Among these are the need to organize neuroscientific data, information, and knowledge to facilitate new scientific endeavors, provide credibility and visibility of research findings, and increase the efficiency of data reuse. Linked Data is a set of principles based on Web technology that can aid this process as it organizes data as an interconnected network of information. This review examines the history, practical impact, potential, and challenges of applying Linked Data principles to neuroscience.

Scientific Communication and Education

Diagnostic assessments of student thinking about stochastic processes.

A number of research studies indicate that students often have difficulties in understanding the presence and/or the implications of stochastic processes within biological systems. While critical to a wide range of phenomena, the presence and implications of stochastic processes are rarely explicitly considered in the course of formal instruction. To help instructors identify gaps in student understanding, we have designed and tested six open source activities covering a range of scenarios, from death rates to noise in gene expression, that can be employed, alone or in combination, as diagnostics to reveal student thinking as a prelude to the presentation of stochastic processes within a course or a curriculum.

Scientific Communication and Education

Illuminating Uveitis: Metagenomic Deep Sequencing Identifies Common and Rare Pathogens

BackgroundOcular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~ 50% of presumed infectious uveitis cases.1,2 We aimed to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.\n\nMethodsThis is a proof-of-concept study, in which intraocular fluid samples were obtained from 5 subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS.\n\nFindingsUnbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n=4) and without (n=1) uveitis. Rubella virus (RV) was identified in one case of chronic bilateral idiopathic uveitis. The subjects strain was most closely related to a German RV strain isolated in 1992, one year before he developed a fever and rash while living in Germany.\n\nInterpretationMDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular RV infection highlights the eyes role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics.

Scientific Communication and Education

Zika in Rio de Janeiro: Assessment of basic reproduction number and comparison with dengue outbreaks

Zika virus infection was declared a public health emergency of international concern in February 2016 in response to the outbreak in Brazil and its suspected link with congenital anomalies. In this study we use notification data and disease natural history parameters to estimate the basic reproduction number (R0) of Zika in Rio de Janeiro, Brazil. We also obtain estimates of R0 of dengue from time series of dengue cases in the outbreaks registered in 2002 and 2012 in the city, when DENV-3 and DENV-4 serotypes respectively, had just emerged. Our estimates of the basic reproduction number for Zika in Rio de Janeiro based on surveillance notifications (R0 = 2.33, 95% CI: 1.97 - 2.97) were higher than those obtained for dengue in the city (year 2002: R0 = 1.70 [1.50 - 2.02]; year 2012: Ro = 1.25 [1.18 - 1.36]). Given the role of Aedes aegypti as vector of both the Zika and dengue viruses, we also derive Ro of Zika as a function of both dengue reproduction number and entomological and epidemiological parameters for dengue and Zika. Using the dengue outbreaks from previous years allowed us to estimate the potential R0 of Zika. Our estimates were closely in agreement with our first Zikas R0 estimation from notification data. Hence, these results validate deriving the potential risk of Zika transmission in areas with recurring dengue outbreaks. Whether transmission routes other than vector-based can sustain a Zika epidemic still deserves attention, but our results suggest that the Zika outbreak in Rio de Janeiro emerged due to population susceptibility and ubiquitous presence of Ae. aegypti.

Scientific Communication and Education

Biogeographic Ancestry and Socioeconomic Outcomes in the Americas: a Meta-analysis

Narrative reports suggest that socioeconomic status (SES) is associated with biogeographic ancestry (BGA) in the Americas. If so, SES potentially acts as a confound that needs to be taken into account when evaluating the relation between medical outcomes and BGA. To explore how systematic BGA-SES associations are, a meta-analysis of American studies was conducted. 41 studies were identified, yielding a total of 64 independent samples with directions of associations, including 48 independent samples with effect sizes. An analysis of association directions found a high degree of consistency. The square root n-weighted directions were 0.83 (K = 36), -0.81 (K = 41) and -0.82 (K = 39) for European, Amerindian and African BGA, respectively. An analysis of effect size magnitudes found that European BGA was positively associated with SES, with a meta-analytic effect size of r = .18 [95% CI: .13 to .24, K = 28, n = 35,476.50], while both Amerindian and African BGA were negatively associated with SES, having meta-analytic effect sizes of -.14 [-.18 to -.10, k =31, n = 28,937.50] and -.11 [-.15 to -.07, K = 28, n = 32,710.50], respectively. There was considerable cross-sample variation in effect sizes (mean I2 = 92%), but the sample size was not enough for performing credible moderator analysis. Implications for future studies are discussed.

Scientific Communication and Education

Learning from critical care management of sheep receiving extra-corporeal membrane oxygenation for smoke-induced acute lung injury as a tool for processing large clinical datasets

BackgroundNumerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. MethodsNineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. ResultsCompared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio. The oxygen extraction index changes mirrored those of the PaO2/FiO2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. ConclusionsThese novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.

Scientific Communication and Education

A formula to estimate a Researcher’s impact by prioritizing highly cited publications

Here we suggest a new index to estimate the scientific impact of an individual researcher, namely the S-index. This index has been designed to emphasize highly cited, truly important works and to be minimally affected by poorly cited ones, without setting any arbitrary threshold. The first property makes it advantageous over the h-index, which does not discriminate between highly and moderately cited articles, while the second property - over the total number of citations, preventing the possibility of overclocking an index by publishing many trivial articles. Contrary to the h-index, which has an upper limit of the total number of publications regardless of their citation numbers, the S-index is not limited by the publication count. This allows scientists having few but very influential works to receive appropriate and respectable index values, which is impossible with the h-index. Moreover, only 10 most cited publications of an individual are typically required to calculate an S-index to 99% accuracy. Collectively, the S-index is principally different from the existing scientometric indicators and should facilitate better recognition of prominent researchers.

Scientific Communication and Education

Scanning the Horizon: challenges and solutions for neuroimaging research

Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors, and lack of direct replication apply to many fields, but perhaps particularly to fMRI. Here we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful answers to neuroscientific questions.

Scientific Communication and Education

A signal detection theoretic argument against claims of unmeritocratic faculty hiring

To get a faculty job, graduating doctoral students have to substantially outperform their peers, given the competitive nature of the academic job market. In an ideal, meritocratic world, factors such as prestige of degree-granting university ought not to play a substantial role. However, it has recently been reported that top-ranked universities produced about 2-6 times more faculty than did universities that were ranked lower (Clauset, Arbesman, and Larremore 2015), necessitating un-meritocratic factors: how could students from top-ranked universities be six times more productive than their peers from lower-ranked universities? Here we present a signal detection model to demonstrate that substantially higher rates of faculty production need not require substantially (and unrealistically) higher levels of student productivity. Instead, it is a high hiring threshold due to keen competition that causes small difference in average student productivity between universities to result in manifold differences in placement rates. Under this framework, the previously reported results are compatible with a purely meritocratic system. As a simple proof of concept, we examined the association between university ranking and the impact factors of students publications from a small selected sample of psychology departments in the U.S. The results are in agreement with our theoretical model. Whereas these results do not necessarily mean that the actual faculty hiring market is purely meritocratic, they highlight the difficulty in empirically demonstrating that it is not so.

Scientific Communication and Education

A simple proposal for the publication of journal citation distributions

Although the Journal Impact Factor (JIF) is widely acknowledged to be a poor indicator of the quality of individual papers, it is used routinely to evaluate research and researchers. Here, we present a simple method for generating the citation distributions that underlie JIFs. Application of this straightforward protocol reveals the full extent of the skew of distributions and variation in citations received by published papers that is characteristic of all scientific journals. Although there are differences among journals across the spectrum of JIFs, the citation distributions overlap extensively, demonstrating that the citation performance of individual papers cannot be inferred from the JIF. We propose that this methodology be adopted by all journals as a move to greater transparency, one that should help to refocus attention on individual pieces of work and counter the inappropriate usage of JIFs during the process of research assessment.

Scientific Communication and Education

A statistical definition for reproducibility and replicability

Everyone agrees that reproducibility and replicability are fundamental characteristics of scientific studies. These topics are attracting increasing attention, scrutiny, and debate both in the popular press and the scientific literature. But there are no formal statistical definitions for these concepts, which leads to confusion since the same words are used for different concepts by different people in different fields. We provide formal and informal definitions of scientific studies, reproducibility, and replicability that can be used to clarify discussions around these concepts in the scientific and popular press.

Scientific Communication and Education

Lost dollars threaten research in public academic health centers

Decreasing federal and state support threaten long-term sustainability of research in publicly supported academic health centers. In weathering these financial threats, research at the University of California, San Francisco (UCSF) has undergone three substantial changes: (i) institutional salary support goes preferentially to senior faculty, while the young increasingly depend on grants; (ii) private and government support for research grows apace in clinical departments, but slowly declines in basic science departments; and (iii) research is judged more on its quantity (numbers of investigators and federal and private dollars) than on its goals, achievements, or scientific quality. We propose measures to alleviate these problems. Other large public academic health centers probably confront similar issues, but--except for UCSF--such centers have not been subjected to detailed public analysis.

Scientific Communication and Education