Most-cited articles · 2018

The 100 most-cited articles in PLoS ONE, 2018

Ranked by OpenAlex citation count on 29 October 2026, out of 17,870 eligible articles PLoS ONE published in 2018. Ranks are frozen; this page will not change. Number one, with 1,899 citations: The Ryerson Audio-Visual Database of Emotional Speech and Song (RAVDESS): A dynamic, multimodal set of facial and vocal expressions in North American English.

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The 2018 PLoS ONE articles with the most citations cluster around several recurring themes. Research tools and datasets are prominent, led by the Ryerson Audio-Visual Database of Emotional Speech and Song (RAVDESS), a multimodal database of emotional speech and song, with 1899 citations, followed by miRWalk, an open-source platform for predicting microRNA binding sites, with 1807 citations. Methodological and forecasting work also ranks highly, including a paper on statistical and machine learning forecasting methods with 1516 citations. Health-related reviews and measures are likewise well represented, such as a systematic review of emergency department crowding and a measure of the 5C psychological antecedents of vaccination.

For readers, the list offers a view of which 2018 PLoS ONE articles were cited most often, as counted by OpenAlex. The entries span database and software resources, forecasting methodology, systematic reviews, and measurement instruments. Because ranking reflects citation counts rather than quality or importance, the list can serve as a starting point for exploring frequently referenced work in these areas.

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  1. 1
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    The Ryerson Audio-Visual Database of Emotional Speech and Song (RAVDESS): A dynamic, multimodal set of facial and vocal expressions in North American English

    Steven Robert Livingstone, Frank Russo

    1,899 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0196391OpenAlex

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    The RAVDESS is a validated multimodal database of emotional speech and song. The database is gender balanced consisting of 24 professional actors, vocalizing lexically-matched statements in a neutral North American accent. Speech includes calm, happy, sad, angry, fearful, surprise, and disgust expressions, and song contains calm, happy, sad, angry, and fearful emotions. Each expression is produced at two levels of emotional intensity, with an additional neutral expression. All conditions are available in face-and-voice, face-only, and voice-only formats. The set of 7356 recordings were each rated 10 times on emotional validity, intensity, and genuineness. Ratings were provided by 247 individuals who were characteristic of untrained research participants from North America. A further set of 72 participants provided test-retest data. High levels of emotional validity and test-retest intrarater reliability were reported. Corrected accuracy and composite "goodness" measures are presented to assist researchers in the selection of stimuli. All recordings are made freely available under a…

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    miRWalk: An online resource for prediction of microRNA binding sites

    Carsten Sticht, Carolina De La Torre, Alisha Parveen, Norbert Gretz

    1,807 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0206239OpenAlex

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    miRWalk is an open-source platform providing an intuitive interface that generates predicted and validated miRNA-binding sites of known genes of human, mouse, rat, dog and cow. The core of miRWalk is the miRNA target site prediction with the random-forest-based approach software TarPmiR searching the complete transcript sequence including the 5'-UTR, CDS and 3'-UTR. Moreover, it integrates results other databases with predicted and validated miRNA-target interactions. The focus is set on a modular design and extensibility as well as a fast update cycle. The database is available using Python, MySQL and HTML/Javascript Database URL: http://mirwalk.umm.uni-heidelberg.de.

  3. 3
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    Statistical and Machine Learning forecasting methods: Concerns and ways forward

    Spyros Makridakis, Evangelos Spiliotis, Vassilios Assimakopoulos

    1,516 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194889OpenAlex

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    Machine Learning (ML) methods have been proposed in the academic literature as alternatives to statistical ones for time series forecasting. Yet, scant evidence is available about their relative performance in terms of accuracy and computational requirements. The purpose of this paper is to evaluate such performance across multiple forecasting horizons using a large subset of 1045 monthly time series used in the M3 Competition. After comparing the post-sample accuracy of popular ML methods with that of eight traditional statistical ones, we found that the former are dominated across both accuracy measures used and for all forecasting horizons examined. Moreover, we observed that their computational requirements are considerably greater than those of statistical methods. The paper discusses the results, explains why the accuracy of ML models is below that of statistical ones and proposes some possible ways forward. The empirical results found in our research stress the need for objective and unbiased ways to test the performance of forecasting methods that can be achieved through…

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    Emergency department crowding: A systematic review of causes, consequences and solutions

    Claire Morley, Maria Unwin, Gregory Mark Peterson, Jim M. Stankovich, Leigh Kinsman

    1,382 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203316OpenAlex

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    BACKGROUND: Emergency department crowding is a major global healthcare issue. There is much debate as to the causes of the phenomenon, leading to difficulties in developing successful, targeted solutions. AIM: The aim of this systematic review was to critically analyse and summarise the findings of peer-reviewed research studies investigating the causes and consequences of, and solutions to, emergency department crowding. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A structured search of four databases (Medline, CINAHL, EMBASE and Web of Science) was undertaken to identify peer-reviewed research publications aimed at investigating the causes or consequences of, or solutions to, emergency department crowding, published between January 2000 and June 2018. Two reviewers used validated critical appraisal tools to independently assess the quality of the studies. The study protocol was registered with the International prospective register of systematic reviews (PROSPERO 2017: CRD42017073439). RESULTS: From 4,131…

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    Beyond confidence: Development of a measure assessing the 5C psychological antecedents of vaccination

    Cornelia Betsch, Philipp Schmid, Dorothee K. Heinemeier, Lars Korn, Cindy Holtmann and 1 more

    1,289 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0208601OpenAlex

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    BACKGROUND: Monitoring the reasons why a considerable number of people do not receive recommended vaccinations allows identification of important trends over time, and designing and evaluating strategies to address vaccine hesitancy and increase vaccine uptake. Existing validated measures assessing vaccine hesitancy focus primarily on confidence in vaccines and the system that delivers them. However, empirical and theoretical work has stated that complacency (not perceiving diseases as high risk), constraints (structural and psychological barriers), calculation (engagement in extensive information searching), and aspects pertaining to collective responsibility (willingness to protect others) also play a role in explaining vaccination behavior. The objective was therefore to develop a validated measure of these 5C psychological antecedents of vaccination. METHODS AND FINDINGS: Three cross-sectional studies were conducted. Study 1 uses factor analysis to develop an initial scale and assesses the sub-scales' convergent, discriminant, and concurrent validity (N = 1,445, two German…

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    Anthropogenic contamination of tap water, beer, and sea salt

    Mary Kosuth, Sherri A. Mason, Elizabeth V. Wattenberg

    1,247 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194970OpenAlex

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    Plastic pollution has been well documented in natural environments, including the open waters and sediments within lakes and rivers, the open ocean and even the air, but less attention has been paid to synthetic polymers in human consumables. Since multiple toxicity studies indicate risks to human health when plastic particles are ingested, more needs to be known about the presence and abundance of anthropogenic particles in human foods and beverages. This study investigates the presence of anthropogenic particles in 159 samples of globally sourced tap water, 12 brands of Laurentian Great Lakes beer, and 12 brands of commercial sea salt. Of the tap water samples analyzed, 81% were found to contain anthropogenic particles. The majority of these particles were fibers (98.3%) between 0.1-5 mm in length. The range was 0 to 61 particles/L, with an overall mean of 5.45 particles/L. Anthropogenic debris was found in each brand of beer and salt. Of the extracted particles, over 99% were fibers. After adjusting for particles found in lab blanks for both salt and beer, the average number of…

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    Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

    Mary Furlan Feitosa, Aldi T. Kraja, Daniel I. Chasman, Yun J. Sung, Thomas W. Winkler and 25 more

    1,165 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0198166OpenAlex

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    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0…

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    Semaphorin3A induces nerve regeneration in the adult cornea-a switch from its repulsive role in development

    Min Zhang, Qiang Zhou, Yuncin Luo, Tara Nguyen, Mark I. Rosenblatt and 1 more

    990 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191962OpenAlex

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    The peripheral sensory nerves that innervate the cornea can be easily damaged by trauma, surgery, infection or diabetes. Several growth factors and axon guidance molecules, such as Semaphorin3A (Sema3A) are upregulated upon cornea injury. Nerves can regenerate after injury but do not recover their original density and patterning. Sema3A is a well known axon guidance and growth cone repellent protein during development, however its role in adult cornea nerve regeneration remains undetermined. Here we investigated the neuro-regenerative potential of Sema3A on adult peripheral nervous system neurons such as those that innervate the cornea. First, we examined the gene expression profile of the Semaphorin class 3 family members and found that all are expressed in the cornea. However, upon cornea injury there is a fast increase in Sema3A expression. We then corroborated that Sema3A totally abolished the growth promoting effect of nerve growth factor (NGF) on embryonic neurons and observed signs of growth cone collapse and axonal retraction after 30 min of Sema3A addition. However, in…

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    The Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2)

    Wolf E. Mehling, Michael C. Acree, Anita L. Stewart, Jonathan Silas, Alexander Jones

    788 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0208034OpenAlex

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    Interoception, the process by which the nervous system senses, interprets, and integrates signals originating from within the body, has become major research topic for mental health and in particular for mind-body interventions. Interoceptive awareness here is defined as the conscious level of interoception with its multiple dimensions potentially accessible to self-report. The Multidimensional Assessment of Interoceptive Awareness (MAIA) is an 8-scale state-trait questionnaire with 32 items to measure multiple dimensions of interoception by self-report and was published in November 2012. Its numerous applications in English and other languages revealed low internal consistency reliability for two of its scales. This study's objective was to improve these scales and the psychometrics of the MAIA by adding three new items to each of the two scales and evaluate these in a new sample. Data were collected within a larger project that took place as part of the Live Science residency programme at the Science Museum London, UK, where visitors to the museum (N = 1,090) completed the MAIA…

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    Enhancing the sample diversity of snowball samples: Recommendations from a research project on anti-dam movements in Southeast Asia

    Julian Kirchherr, Katrina Charles

    754 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0201710OpenAlex

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    Snowball sampling is a commonly employed sampling method in qualitative research; however, the diversity of samples generated via this method has repeatedly been questioned. Scholars have posited several anecdotally based recommendations for enhancing the diversity of snowball samples. In this study, we performed the first quantitative, medium-N analysis of snowball sampling to identify pathways to sample diversity, analysing 211 reach-outs conducted via snowball sampling, resulting in 81 interviews; these interviews were administered between April and August 2015 for a research project on anti-dam movements in Southeast Asia. Based upon this analysis, we were able to refine and enhance the previous recommendations (e.g., showcasing novel evidence on the value of multiple seeds or face-to-face interviews). This paper may thus be of particular interest to scholars employing or intending to employ snowball sampling.

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    Building long-term empathy: A large-scale comparison of traditional and virtual reality perspective-taking

    Fernanda Herrera, Jeremy N. Bailenson, Erika Weisz, Elise Ogle, Jamil Zaki

    720 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204494OpenAlex

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    Virtual Reality (VR) has been increasingly referred to as the "ultimate empathy machine" since it allows users to experience any situation from any point of view. However, empirical evidence supporting the claim that VR is a more effective method of eliciting empathy than traditional perspective-taking is limited. Two experiments were conducted in order to compare the short and long-term effects of a traditional perspective-taking task and a VR perspective-taking task (Study 1), and to explore the role of technological immersion when it comes to different types of mediated perspective-taking tasks (Study 2). Results of Study 1 show that over the course of eight weeks participants in both conditions reported feeling empathetic and connected to the homeless at similar rates, however, participants who became homeless in VR had more positive, longer-lasting attitudes toward the homeless and signed a petition supporting the homeless at a significantly higher rate than participants who performed a traditional perspective-taking task. Study 2 compared three different types of…

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    Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses

    Vanesa Bellou, Lazaros Belbasis, Ioanna Tzoulaki, Εvangelos Εvangelou

    713 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194127OpenAlex

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    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed. METHODS: We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria. RESULTS: We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adiposity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption…

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    Incidence and prevalence of patellofemoral pain: A systematic review and meta-analysis

    Benjamin Edward Smith, James Selfe, Damian Thacker, Paul A. Hendrick, Marcus Bateman and 4 more

    679 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0190892OpenAlex

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    BACKGROUND: Patellofemoral pain is considered one of the most common forms of knee pain, affecting adults, adolescents, and physically active populations. Inconsistencies in reported incidence and prevalence exist and in relation to the allocation of healthcare and research funding, there is a clear need to accurately understand the epidemiology of patellofemoral pain. METHODS: An electronic database search was conducted, as well as grey literature databases, from inception to June 2017. Two authors independently selected studies, extracted data and appraised methodological quality. If heterogeneous, data were analysed descriptively. Where studies were homogeneous, data were pooled through a meta-analysis. RESULTS: 23 studies were included. Annual prevalence for patellofemoral pain in the general population was reported as 22.7%, and adolescents as 28.9%. Incidence rates in military recruits ranged from 9.7-571.4/1,000 person-years, amateur runners in the general population at 1080.5/1,000 person-years and adolescents amateur athletes 5.1%-14.9% over 1 season. One study reported…

  14. 14
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    Association of loneliness with all-cause mortality: A meta-analysis

    Laura Alejandra Rico‐Uribe, Francisco Félix Caballero, Natalia Martín‐María, María Cabello, José Luís Ayuso‐Mateos and 1 more

    651 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0190033OpenAlex

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    INTRODUCTION: Loneliness has social and health implications. The aim of this article is to evaluate the association of loneliness with all-cause mortality. METHODS: Pubmed, PsycINFO, CINAHL and Scopus databases were searched through June 2016 for published articles that measured loneliness and mortality. The main characteristics and the effect size values of each article were extracted. Moreover, an evaluation of the quality of the articles included was also carried out. A meta-analysis was performed firstly with all the included articles and secondly separating by gender, using a random effects model. RESULTS: A total of 35 articles involving 77220 participants were included in the systematic review. Loneliness is a risk factor for all-cause mortality [pooled HR = 1.22, 95% CI = (1.10, 1.35), p < 0.001] for both genders together, and for women [pooled HR = 1.26, 95% CI = (1.07, 1.48); p = 0.005] and men [pooled HR = 1.44; 95% CI = (1.19, 1.76); p < 0.001] separately. CONCLUSIONS: Loneliness shows a harmful effect for all-cause mortality and this effect is slightly stronger in men…

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    Single-nucleus and single-cell transcriptomes compared in matched cortical cell types

    Trygve E. Bakken, Rebecca D. Hodge, Jeremy A. Miller, Zizhen Yao, Thuc Nghi Nguyen and 23 more

    608 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0209648OpenAlex

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    Transcriptomic profiling of complex tissues by single-nucleus RNA-sequencing (snRNA-seq) affords some advantages over single-cell RNA-sequencing (scRNA-seq). snRNA-seq provides less biased cellular coverage, does not appear to suffer cell isolation-based transcriptional artifacts, and can be applied to archived frozen specimens. We used well-matched snRNA-seq and scRNA-seq datasets from mouse visual cortex to compare cell type detection. Although more transcripts are detected in individual whole cells (~11,000 genes) than nuclei (~7,000 genes), we demonstrate that closely related neuronal cell types can be similarly discriminated with both methods if intronic sequences are included in snRNA-seq analysis. We estimate that the nuclear proportion of total cellular mRNA varies from 20% to over 50% for large and small pyramidal neurons, respectively. Together, these results illustrate the high information content of nuclear RNA for characterization of cellular diversity in brain tissues.

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    Burnout syndrome among medical residents: A systematic review and meta-analysis

    Hugo Rodrigues, Ricardo Ney Cobucci, António Gouveia Oliveira, João Victor Cabral, Leany Medeiros and 3 more

    589 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0206840OpenAlex

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    BACKGROUND: Burnout is a psychological syndrome that is very common among medical residents. It consists of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). OBJECTIVE: To estimate burnout among different medical residency specialties. METHODS: A systematic review with meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of bibliographic databases and grey literature was conducted, from inception to March 2018. The following databases were accessed: Embase, PubMed, Web of Science, Google Scholar and Scopus, and 3,575 studies were found. Methodological quality was evaluated by Agency for Healthcare Research and Quality Methodology Checklist for Cross-Sectional/Prevalence Study. In the final analysis, 26 papers were included. Their references were checked for additional studies, but none were included. RESULTS: 4,664 medical residents were included. High DP, EE and low PA proportions were compared. Specialties were distributed into three groups of different…

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    Production of methane and ethylene from plastic in the environment

    Sarah‐Jeanne Royer, Sara Ferrón, Samuel T. Wilson, David M. Karl

    572 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200574OpenAlex

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    Mass production of plastics started nearly 70 years ago and the production rate is expected to double over the next two decades. While serving many applications because of their durability, stability and low cost, plastics have deleterious effects on the environment. Plastic is known to release a variety of chemicals during degradation, which has a negative impact on biota. Here, we show that the most commonly used plastics produce two greenhouse gases, methane and ethylene, when exposed to ambient solar radiation. Polyethylene, which is the most produced and discarded synthetic polymer globally, is the most prolific emitter of both gases. We demonstrate that the production of trace gases from virgin low-density polyethylene increase with time, with rates at the end of a 212-day incubation of 5.8 nmol g-1 d-1 of methane, 14.5 nmol g-1 d-1 of ethylene, 3.9 nmol g-1 d-1 of ethane and 9.7 nmol g-1 d-1 of propylene. Environmentally aged plastics incubated in water for at least 152 days also produced hydrocarbon gases. In addition, low-density polyethylene emits these gases when…

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    Open-ended interview questions and saturation

    Susan C. Weller, Ben Vickers, H. Russell Bernard, Alyssa Blackburn, Stephen P. Borgatti and 2 more

    561 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0198606OpenAlex

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    Sample size determination for open-ended questions or qualitative interviews relies primarily on custom and finding the point where little new information is obtained (thematic saturation). Here, we propose and test a refined definition of saturation as obtaining the most salient items in a set of qualitative interviews (where items can be material things or concepts, depending on the topic of study) rather than attempting to obtain all the items. Salient items have higher prevalence and are more culturally important. To do this, we explore saturation, salience, sample size, and domain size in 28 sets of interviews in which respondents were asked to list all the things they could think of in one of 18 topical domains. The domains-like kinds of fruits (highly bounded) and things that mothers do (unbounded)-varied greatly in size. The datasets comprise 20-99 interviews each (1,147 total interviews). When saturation was defined as the point where less than one new item per person would be expected, the median sample size for reaching saturation was 75 (range = 15-194). Thematic…

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    Prevalence of psychotic disorders and its association with methodological issues. A systematic review and meta-analyses

    Berta Moreno‐Küstner, Carlos Martín, L. Delgado Pastor

    561 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195687OpenAlex

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    OBJECTIVES: The purpose of this study is to provide an updated systematic review to identify studies describing the prevalence of psychosis in order to explore methodological factors that could account for the variation in prevalence estimates. METHODS: Studies with original data related to the prevalence of psychosis (published between 1990 and 2015) were identified via searching electronic databases and reviewing manual citations. Prevalence estimates were sorted according to prevalence type (point, 12-months and lifetime). The independent association between key methodological variables and the mean effect of prevalence was examined (prevalence type, case-finding setting, method of confirming diagnosis, international classification of diseases, diagnosis category, and study quality) by meta-analytical techniques and random-effects meta-regression. RESULTS: Seventy-three primary studies were included, providing a total of 101 estimates of prevalence rates of psychosis. Across these studies, the pooled median point and 12-month prevalence for persons was 3.89 and 4.03 per 1000…

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    What matters to women during childbirth: A systematic qualitative review

    Soo M. Downe, Kenneth William Finlayson, Olufemi Taiwo Oladapo, Mercedes Bonet, Ahmet Metin Gülmezoglu

    549 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194906OpenAlex

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    INTRODUCTION: Design and provision of good quality maternity care should incorporate what matters to childbearing women. This qualitative systematic review was undertaken to inform WHO intrapartum guidelines. METHODS: Using a pre-determined search strategy, we searched Medline, CINAHL, PsycINFO, AMED, EMBASE, LILACS, AJOL, and reference lists of eligible studies published 1996-August 2016 (updated to January 2018), reporting qualitative data on womens' childbirth beliefs, expectations, and values. Studies including specific interventions or health conditions were excluded. PRISMA guidelines were followed. DATA COLLECTION AND ANALYSIS: Authors' findings were extracted, logged on a study-specific data form, and synthesised using meta-ethnographic techniques. Confidence in the quality, coherence, relevance and adequacy of data underpinning the resulting themes was assessed using GRADE-CERQual. A line of argument synthesis was developed. RESULTS: 35 studies (19 countries) were included in the primary search, and 2 in the update. Confidence in most results was moderate to high. What…

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    Effectiveness of school food environment policies on children’s dietary behaviors: A systematic review and meta-analysis

    Renata Micha, Dimitra Karageorgou, Ioanna Bakogianni, Eirini Trichia, Laurie P. Whitsel and 3 more

    526 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194555OpenAlex

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    BACKGROUND: School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear. OBJECTIVE: To systematically review and quantify the impact of school food environment policies on dietary habits, adiposity, and metabolic risk in children. METHODS: We systematically searched online databases for randomized or quasi-experimental interventions assessing effects of school food environment policies on children's dietary habits, adiposity, or metabolic risk factors. Data were extracted independently and in duplicate, and pooled using inverse-variance random-effects meta-analysis. Habitual (within+outside school) dietary intakes were the primary outcome. Heterogeneity was explored using meta-regression and subgroup analysis. Funnel plots, Begg's and Egger's test evaluated potential publication bias. RESULTS: From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in Europe/New Zealand) were included, on direct provision of healthful foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29), and…

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    Monitoring and predicting land use and land cover changes using remote sensing and GIS techniques—A case study of a hilly area, Jiangle, China

    Chen Li-ping, Sun Yujun, Sajjad Saeed

    511 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200493OpenAlex

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    Land use and land cover change research has been applied to landslides, erosion, land planning and global change. Based on the CA-Markov model, this study predicts the spatial patterns of land use in 2025 and 2036 based on the dynamic changes in land use patterns using remote sensing and geographic information system. CA-Markov integrates the advantages of cellular automata and Markov chain analysis to predict future land use trends based on studies of land use changes in the past. Based on Landsat 5 TM images from 1992 and 2003 and Landsat 8 OLI images from 2014, this study obtained a land use classification map for each year. Then, the genetic transition probability from 1992 to 2003 was obtained by IDRISI software. Based on the CA-Markov model, a predicted land use map for 2014 was obtained, and it was validated by the actual land use results of 2014 with a Kappa index of 0.8128. Finally, the land use patterns of 2025 and 2036 in Jiangle County were determined. This study can provide suggestions and a basis for urban development planning in Jiangle County.

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    Evaluating collinearity effects on species distribution models: An approach based on virtual species simulation

    Paulo de Marco Júnior, Caroline Corrêa Nóbrega

    483 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0202403OpenAlex

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    The increasing use of species distribution modeling (SDM) has raised new concerns regarding the inaccuracies, misunderstanding, and misuses of this important tool. One of those possible pitfalls - collinearity among environmental predictors - is assumed as an important source of model uncertainty, although it has not been subjected to a detailed evaluation in recent SDM studies. It is expected that collinearity will increase uncertainty in model parameters and decrease statistical power. Here we use a virtual species approach to compare models built using subsets of PCA-derived variables with models based on the original highly correlated climate variables. Moreover, we evaluated whether modelling algorithms and species data characteristics generate models with varying sensitivity to collinearity. As expected, collinearity among predictors decreases the efficiency and increases the uncertainty of species distribution models. Nevertheless, the intensity of the effect varied according to the algorithm properties: more complex procedures behaved better than simple envelope models. This…

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    The relationship between greenspace and the mental wellbeing of adults: A systematic review

    Victoria Houlden, Scott Weich, João Porto de Albuquerque, Stephen A. Jarvis, Karen Rees

    471 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203000OpenAlex

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    INTRODUCTION: The view that interacting with nature enhances mental wellbeing is commonplace, despite a dearth of evidence or even agreed definitions of 'nature'. The aim of this review was to systematically appraise the evidence for associations between greenspace and mental wellbeing, stratified by the different ways in which greenspace has been conceptualised in quantitative research. METHODS: We undertook a comprehensive database search and thorough screening of articles which included a measure of greenspace and validated mental wellbeing tool, to capture aspects of hedonic and/or eudaimonic wellbeing. Quality and risk of bias in research were assessed to create grades of evidence. We undertook detailed narrative synthesis of the 50 studies which met the review inclusion criteria, as methodological heterogeneity precluded meta-analysis. RESULTS: Results of a quality assessment and narrative synthesis suggest associations between different greenspace characteristics and mental wellbeing. We identified six ways in which greenspace was conceptualised and measured: (i) amount of…

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    Systematic review and meta-analysis of Mental Health First Aid training: Effects on knowledge, stigma, and helping behaviour

    Amy Joanna Morgan, Anna Ross, Nicola Jane Reavley

    460 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0197102OpenAlex

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    OBJECTIVE: To provide an up-to-date assessment of the effectiveness of the Mental Health First Aid (MHFA) training program on improving mental health knowledge, stigma and helping behaviour. DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of electronic databases was conducted in October 2017 to identify randomised controlled trials or controlled trials of the MHFA program. Eligible trials were in adults, used any comparison condition, and assessed one or more of the following outcomes: mental health first aid knowledge; recognition of mental disorders; treatment knowledge; stigma and social distance; confidence in or intentions to provide mental health first aid; provision of mental health first aid; mental health of trainees or recipients of mental health first aid. Risk of bias was assessed and effect sizes (Cohen's d) were pooled using a random effects model. Separate meta-analyses examined effects at post-training, up to 6 months post-training, and greater than 6 months post-training. RESULTS: A total of 18 trials (5936 participants) were included.…

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    Biodegradability of polyethylene by bacteria and fungi from Dandora dumpsite Nairobi-Kenya

    Christabel Ndahebwa Muhonja, Huxley Mae Makonde, Gabriel N. Magoma, Mabel Imbuga

    452 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0198446OpenAlex

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    This study aimed at isolating and identifying bacteria and fungi with the capacity to degrade low density polyethylene (LDPE). The level of biodegradation of LDPE sheets with bacterial and fungal inoculums from different sampling points of Dandora dumpsite was evaluated under laboratory conditions. Incubation of the LDPE sheets was done for sixteen weeks at 37°C and 28°C for bacteria and fungi respectively in a shaker incubator. Isolation of effective candidates for biodegradation was done based on the recorded biodegradation outcomes. The extent of biodegradation on the polyethylene sheets was assessed by various techniques including weight loss analysis, Fourier Transform Infrared Spectroscopy (FTIR) and GC-MS. Fourier Transform Infra-Red spectroscopy (FTIR) analysis revealed the appearance of new functional groups attributed to hydrocarbon degradation after incubation with the bacteria and fungi. Analysis of the 16S rDNA and 18S rDNA sequences for bacteria and fungi respectively showed that bacteria belonging to genera Pseudomonas, Bacillus, Brevibacillus, Cellulosimicrobium,…

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    Remarkable agrivoltaic influence on soil moisture, micrometeorology and water-use efficiency

    Elnaz Hassanpour Adeh, John Steven Selker, Chad W. Higgins

    447 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203256OpenAlex

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    Power demands are set to increase by two-fold within the current century and a high fraction of that demand should be met by carbon free sources. Among the renewable energies, solar energy is among the fastest growing; therefore, a comprehensive and accurate design methodology for solar systems and how they interact with the local environment is vital. This paper addresses the environmental effects of solar panels on an unirrigated pasture that often experiences water stress. Changes to the microclimatology, soil moisture, water usage, and biomass productivity due to the presence of solar panels were quantified. The goal of this study was to show that the impacts of these factors should be considered in designing the solar farms to take advantage of potential net gains in agricultural and power production. Microclimatological stations were placed in the Rabbit Hills agrivoltaic solar arrays, located in Oregon State campus, two years after the solar array was installed. Soil moisture was quantified using neutron probe readings. Significant differences in mean air temperature,…

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    Global trends of local ecological knowledge and future implications

    Shankar Aswani, Anne Lemahieu, WHH Sauer

    431 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195440OpenAlex

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    Local and indigenous knowledge is being transformed globally, particularly being eroded when pertaining to ecology. In many parts of the world, rural and indigenous communities are facing tremendous cultural, economic and environmental changes, which contribute to weaken their local knowledge base. In the face of profound and ongoing environmental changes, both cultural and biological diversity are likely to be severely impacted as well as local resilience capacities from this loss. In this global literature review, we analyse the drivers of various types of local and indigenous ecological knowledge transformation and assess the directionality of the reported change. Results of this analysis show a global impoverishment of local and indigenous knowledge with 77% of papers reporting the loss of knowledge driven by globalization, modernization, and market integration. The recording of this loss, however, is not symmetrical, with losses being recorded more strongly in medicinal and ethnobotanical knowledge. Persistence of knowledge (15% of the studies) occurred in studies where…

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    Gender disparities in high-quality research revealed by Nature Index journals

    M. H. K. Bendels, Ruth Müller, Doerthe Brueggmann, David Alexander Groneberg

    428 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0189136OpenAlex

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    BACKGROUND: The present study aims to elucidate the state of gender equality in high-quality research by analyzing the representation of female authorships in the last decade (from 2008 to 2016). METHODS: Based on the Gendermetrics platform, 293,557 research articles from 54 journals listed in the Nature Index were considered covering the categories Life Science, Multidisciplinary, Earth & Environmental and Chemistry. The core method was the combined analysis of the proportion of female authorships and the female-to-male odds ratio for first, co- and last authorships. The distribution of prestigious authorships was measured by the Prestige Index. RESULTS: 29.8% of all authorships and 33.1% of the first, 31.8% of the co- and 18.1% of the last authorships were held by women. The corresponding female-to-male odds ratio is 1.19 (CI: 1.18-1.20) for first, 1.35 (CI: 1.34-1.36) for co- and 0.47 (CI: 0.46-0.48) for last authorships. Women are underrepresented at prestigious authorships compared to men (Prestige Index = -0.42). The underrepresentation accentuates in highly competitive…

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    Echo chambers and viral misinformation: Modeling fake news as complex contagion

    Petter Törnberg

    422 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203958OpenAlex

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    The viral spread of digital misinformation has become so severe that the World Economic Forum considers it among the main threats to human society. This spread have been suggested to be related to the similarly problematized phenomenon of "echo chambers", but the causal nature of this relationship has proven difficult to disentangle due to the connected nature of social media, whose causality is characterized by complexity, non-linearity and emergence. This paper uses a network simulation model to study a possible relationship between echo chambers and the viral spread of misinformation. It finds an "echo chamber effect": the presence of an opinion and network polarized cluster of nodes in a network contributes to the diffusion of complex contagions, and there is a synergetic effect between opinion and network polarization on the virality of misinformation. The echo chambers effect likely comes from that they form the initial bandwagon for diffusion. These findings have implication for the study of the media logic of new social media.

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    Heart rate variability in type 2 diabetes mellitus: A systematic review and meta–analysis

    Thomas Benichou, Bruno Pereira, Martial Mermillod, Igor Tauveron, Daniela Melitta Pfabigan and 2 more

    419 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195166OpenAlex

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    BACKGROUND: Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is the gold standard to measure cardiac autonomic neuropathy. We aimed to conduct a systematic review and meta-analysis to evaluate the impact of T2DM on HRV parameters. METHODS: The PubMed, Cochrane Library, Embase and Science Direct databases were searched on 1st October 2017 using the keywords "diabetes" AND ("heart rate variability" OR "HRV"). Included articles had to report HRV parameters in T2DM patients and healthy controls measured during 24 hours with a Holter-electrocardiogram. Measurements of HRV retieved were: RR-intervals (or Normal to Normal intervals-NN), standard deviation of RR intervals (SDNN), percetange of adjacent NN intervals differing by more than 50 milliseconds (pNN50), square root of the mean squared difference of successive RR intervals (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio, as per Task Force recommendations. RESULTS: We included twenty-five…

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    Effects of Mindfulness-Based Stress Reduction on employees’ mental health: A systematic review

    Math Janssen, Yvonne F. Heerkens, Wietske Kuijer‐Siebelink, BEATRICE I. J. M. VAN DER HEIJDEN, Josephine A. Engels

    415 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191332OpenAlex

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    OBJECTIVES: The purpose of this exploratory study was to obtain greater insight into the effects of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT) on the mental health of employees. METHODS: Using PsycINFO, PubMed, and CINAHL, we performed a systematic review in October 2015 of studies investigating the effects of MBSR and MBCT on various aspects of employees' mental health. Studies with a pre-post design (i.e. without a control group) were excluded. RESULTS: 24 articles were identified, describing 23 studies: 22 on the effects of MBSR and 1 on the effects of MBSR in combination with some aspects of MBCT. Since no study focused exclusively on MBCT, its effects are not described in this systematic review. Of the 23 studies, 2 were of high methodological quality, 15 were of medium quality and 6 were of low quality. A meta-analysis was not performed due to the emergent and relatively uncharted nature of the topic of investigation, the exploratory character of this study, and the diversity of outcomes in the studies reviewed. Based on our…

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    Estimated global overweight and obesity burden in pregnant women based on panel data model

    Cheng Chen, Xianglong Xu, Yan Yan

    414 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0202183OpenAlex

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    OBJECTIVE: To estimate the global and country-level burden of overweight and obesity among pregnant women from 2005 to 2014. METHODS: Publicly accessible country-level data were collected from the World Health Organization, the World Bank and the Food and Agricultural Organization. We estimated the number of overweight and obese pregnant women among 184 countries and determined the time-related trend from 2005 to 2014. Based on panel data model, we determined the effects of food energy supply, urbanization, gross national income and female employment on the number of overweight and obese pregnant women. RESULTS: We estimated that 38.9 million overweight and obese pregnant women and 14.6 million obese pregnant women existed globally in 2014. In upper middle income countries and lower middle income countries, there were sharp increases in the number of overweight and obese pregnant women. In 2014, the percentage of female with overweight and obesity in India was 21.7%, and India had the largest number of overweight and obese pregnant women (4.3 million), which accounted for 11.1% in…

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    Involving men to improve maternal and newborn health: A systematic review of the effectiveness of interventions

    Mariam Tokhi, Liz Comrie‐Thomson, Jessica Davis, Anayda Gerarda Portela, Matthew Chersich and 1 more

    414 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191620OpenAlex

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    BACKGROUND: Emerging evidence and program experience indicate that engaging men in maternal and newborn health can have considerable health benefits for women and children in low- and middle-income countries. Previous reviews have identified male involvement as a promising intervention, but with a complex evidence base and limited direct evidence of effectiveness for mortality and morbidity outcomes. OBJECTIVE: To determine the effect of interventions to engage men during pregnancy, childbirth and infancy on mortality and morbidity, as well as effects on mechanisms by which male involvement is hypothesised to influence mortality and morbidity outcomes: home care practices, care-seeking, and couple relationships. METHODS: Using a comprehensive, highly sensitive mapping of maternal health intervention studies conducted in low- and middle-income countries between 2000 and 2012, we identified interventions that have engaged men to improve maternal and newborn health. Primary outcomes were care-seeking for essential services, mortality and morbidity, and home care practices. Secondary…

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    Effectiveness of Motivational Interviewing on adult behaviour change in health and social care settings: A systematic review of reviews

    Helen Frost, Pauline Campbell, Margaret Maxwell, Ronan E. O’Carroll, Stephan U Dombrowski and 4 more

    413 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204890OpenAlex

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    BACKGROUND: The challenge of addressing unhealthy lifestyle choice is of global concern. Motivational Interviewing has been widely implemented to help people change their behaviour, but it is unclear for whom it is most beneficial. This overview aims to appraise and synthesise the review evidence for the effectiveness of Motivational Interviewing on health behaviour of adults in health and social care settings. METHODS: A systematic review of reviews. Methods were pre-specified and documented in a protocol (PROSPERO-CRD42016049278). We systematically searched 7 electronic databases: CDSR; DARE; PROSPERO; MEDLINE; CINAHL; AMED and PsycINFO from 2000 to May 2018. Two reviewers applied pre-defined selection criteria, extracted data using TIDIER guidelines and assessed methodological quality using the ROBIS tool. We used GRADE criteria to rate the strength of the evidence for reviews including meta-analyses. FINDINGS: Searches identified 5222 records. One hundred and four reviews, including 39 meta-analyses met the inclusion criteria. Most meta-analysis evidence was graded as low or…

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    Effect of maternal age on the risk of preterm birth: A large cohort study

    F. Fuchs, Barbara Monet, Thiérry Ducruet, Nils Chaillet, François Audibert

    412 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191002OpenAlex

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    BACKGROUND: Maternal age at pregnancy is increasing worldwide as well as preterm birth. However, the association between prematurity and advanced maternal age remains controversial. OBJECTIVE: To evaluate the impact of maternal age on the occurrence of preterm birth after controlling for multiple known confounders in a large birth cohort. STUDY DESIGN: Retrospective cohort study using data from the QUARISMA study, a large Canadian randomized controlled trial, which collected data from 184,000 births in 32 hospitals. Inclusion criteria were maternal age over 20 years. Exclusion criteria were multiple pregnancy, fetal malformation and intra-uterine fetal death. Five maternal age categories were defined and compared for maternal characteristics, gestational and obstetric complications, and risk factors for prematurity. Risk factors for preterm birth <37 weeks, either spontaneous or iatrogenic, were evaluated for different age groups using multivariate logistic regression. RESULTS: 165,282 births were included in the study. Chronic hypertension, assisted reproduction techniques,…

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    The twenty most charismatic species

    Céline Albert, Gloria M. Luque, Franck Courchamp

    403 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0199149OpenAlex

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    Charisma is a term commonly used in conservation biology to describe species. However, as the term "charismatic species" has never been properly defined, it needs to be better characterized to fully meet its potential in conservation biology. To provide a more complete depiction, we collected information from four different sources to define the species currently considered to be the most charismatic and to understand what they represent to the Western public. First, we asked respondents of two separate surveys to identify the 10 animal species that they considered to be the most charismatic and associate them with one to six traits: Rare, Endangered, Beautiful, Cute, Impressive, and Dangerous. We then identified the wild animals featured on the website homepages of the zoos situated in the world's 100 largest cities as well as on the film posters of all Disney and Pixar films, assuming in both cases that the most charismatic species were generally chosen to attract viewers. By combining the four approaches, we set up a ranked list of the 20 most charismatic animals. The majority…

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    A novel attention-based hybrid CNN-RNN architecture for sEMG-based gesture recognition

    Yu Hu, Yongkang Wong, Wentao Wei, Yu Du, Mohan Kankanhalli and 1 more

    399 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0206049OpenAlex

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    The surface electromyography (sEMG)-based gesture recognition with deep learning approach plays an increasingly important role in human-computer interaction. Existing deep learning architectures are mainly based on Convolutional Neural Network (CNN) architecture which captures spatial information of electromyogram signal. Motivated by the sequential nature of electromyogram signal, we propose an attention-based hybrid CNN and RNN (CNN-RNN) architecture to better capture temporal properties of electromyogram signal for gesture recognition problem. Moreover, we present a new sEMG image representation method based on a traditional feature vector which enables deep learning architectures to extract implicit correlations between different channels for sparse multi-channel electromyogram signal. Extensive experiments on five sEMG benchmark databases show that the proposed method outperforms all reported state-of-the-art methods on both sparse multi-channel and high-density sEMG databases. To compare with the existing works, we set the window length to 200ms for NinaProDB1 and NinaProDB2,…

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    Automatic detection of cyberbullying in social media text

    Cynthia Van Hee, Gilles Jacobs, Chris Emmery, Bart Desmet, Els Lefever and 4 more

    385 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203794OpenAlex

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    While social media offer great communication opportunities, they also increase the vulnerability of young people to threatening situations online. Recent studies report that cyberbullying constitutes a growing problem among youngsters. Successful prevention depends on the adequate detection of potentially harmful messages and the information overload on the Web requires intelligent systems to identify potential risks automatically. The focus of this paper is on automatic cyberbullying detection in social media text by modelling posts written by bullies, victims, and bystanders of online bullying. We describe the collection and fine-grained annotation of a cyberbullying corpus for English and Dutch and perform a series of binary classification experiments to determine the feasibility of automatic cyberbullying detection. We make use of linear support vector machines exploiting a rich feature set and investigate which information sources contribute the most for the task. Experiments on a hold-out test set reveal promising results for the detection of cyberbullying-related posts. After…

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    Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria

    Lisa L. Littman

    377 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0202330OpenAlex

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    PURPOSE: In on-line forums, parents have reported that their children seemed to experience a sudden or rapid onset of gender dysphoria, appearing for the first time during puberty or even after its completion. Parents describe that the onset of gender dysphoria seemed to occur in the context of belonging to a peer group where one, multiple, or even all of the friends have become gender dysphoric and transgender-identified during the same timeframe. Parents also report that their children exhibited an increase in social media/internet use prior to disclosure of a transgender identity. Recently, clinicians have reported that post-puberty presentations of gender dysphoria in natal females that appear to be rapid in onset is a phenomenon that they are seeing more and more in their clinic. Academics have raised questions about the role of social media in the development of gender dysphoria. The purpose of this study was to collect data about parents’ observations, experiences, and perspectives about their adolescent and young adult (AYA) children showing signs of an apparent sudden or…

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    Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages

    Bartłomiej Taciak, Maciej Białasek, Agata Braniewska, Zuzanna Sas, Paulina Sawicka and 3 more

    377 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0198943OpenAlex

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    Established cell lines are widely used in research, however an appealing question is the comparability of the cells between various laboratories, their characteristics and stability in time. Problematic is also the cell line misidentification, genetic and phenotypic shift or Mycoplasma contamination which are often forgotten in research papers. The monocyte/macrophage-like cell line RAW 264.7 has been one of the most commonly used myeloid cell line for more than 40 years. Despite its phenotypic and functional stability is often discussed in literature or at various scientific discussion panels, their stability during the consecutive passages has not been confirmed in any solid study. So far, only a few functional features of these cells have been studied, for example their ability to differentiate into osteoclasts. Therefore, in the present paper we have investigated the phenotype and functional stability of the RAW 264.7 cell line from passage no. 5 till passage no. 50. We found out that the phenotype (expression of particular macrophage-characteristic genes and surface markers)…

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    Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice

    Vladimir Ilievski, Paulina Zuchowska, Stefan J. Green, Péter T. Tóth, Michael E. Ragozzino and 5 more

    371 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204941OpenAlex

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    BACKGROUND: The results from cross sectional and longitudinal studies show that periodontitis is closely associated with cognitive impairment (CI) and Alzhemer's Disease (AD). Further, studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain. However, neuropathology resulting from Pg oral application is not known. In this work, we tested the hypothesis that repeated exposure of wild type C57BL/6 mice to orally administered Pg results in neuroinflammation, neurodegeneration, microgliosis, astrogliosis and formation of intra- and extracellular amyloid plaque and neurofibrillary tangles (NFTs) which are pathognomonic signs of AD. METHODS: Experimental chronic periodontitis was induced in ten wild type 8-week old C57BL/6 WT mice by repeated oral application (MWF/week) of Pg/gingipain for 22 weeks (experimental group). Another 10 wild type 8-week old C57BL/6 mice received vehicle alone (control…

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    Exosome isolation from distinct biofluids using precipitation and column-based approaches

    Tânia Soares Martins, José A. M. Catita, Ilka Martins Rosa, Odete A. B. da Cruz e Silva, Ana Gabriela Henriques

    369 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0198820OpenAlex

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    The potential of exosomes as biomarker resources for diagnostics, prognostics and even for therapeutics is an area of intense research. Despite the various approaches available, there is no consensus with respect to the best methodology for isolating exosomes and to provide substantial yields with reliable quality. Differential centrifugation is the most commonly used method but it is time-consuming and requires large sample volumes, thus alternative methods are urgently needed. In this study two precipitation-based methods and one column-based approach were compared for exosome isolation from distinct biofluids (serum, plasma and cerebrospinal fluid). Exosome characterization included morphological analyses, determination of particle concentration, stability and exosome preparations' purity, using different complementary approaches such as Nanoparticle Tracking Analysis, Electrophoretic Light Scattering, Transmission Electron Microscopy, EXOCET colorimetric assay, protein quantification methods and western blotting. The three commercial kits tested successfully isolated exosomes…

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    The influence of political ideology and trust on willingness to vaccinate

    Bert O. Baumgaertner, Juliet E. Carlisle, Florian Justwan

    361 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191728OpenAlex

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    In light of the increasing refusal of some parents to vaccinate children, public health strategies have focused on increasing knowledge and awareness based on a "knowledge-deficit" approach. However, decisions about vaccination are based on more than mere knowledge of risks, costs, and benefits. Individual decision making about vaccinating involves many other factors including those related to emotion, culture, religion, and socio-political context. In this paper, we use a nationally representative internet survey in the U.S. to investigate socio-political characteristics to assess attitudes about vaccination. In particular, we consider how political ideology and trust affect opinions about vaccinations for flu, pertussis, and measles. Our findings demonstrate that ideology has a direct effect on vaccine attitudes. In particular, conservative respondents are less likely to express pro-vaccination beliefs than other individuals. Furthermore, ideology also has an indirect effect on immunization propensity. The ideology variable predicts an indicator capturing trust in government…

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    Relationship between food waste, diet quality, and environmental sustainability

    Zach Conrad, Meredith T. Niles, Deborah A. Neher, Eric D. Roy, Nicole Tichenor Blackstone and 1 more

    360 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0195405OpenAlex

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    Improving diet quality while simultaneously reducing environmental impact is a critical focus globally. Metrics linking diet quality and sustainability have typically focused on a limited suite of indicators, and have not included food waste. To address this important research gap, we examine the relationship between food waste, diet quality, nutrient waste, and multiple measures of sustainability: use of cropland, irrigation water, pesticides, and fertilizers. Data on food intake, food waste, and application rates of agricultural amendments were collected from diverse US government sources. Diet quality was assessed using the Healthy Eating Index-2015. A biophysical simulation model was used to estimate the amount of cropland associated with wasted food. This analysis finds that US consumers wasted 422g of food per person daily, with 30 million acres of cropland used to produce this food every year. This accounts for 30% of daily calories available for consumption, one-quarter of daily food (by weight) available for consumption, and 7% of annual cropland acreage. Higher quality…

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    Effective injury forecasting in soccer with GPS training data and machine learning

    Alessio Rossi, Luca Pappalardo, Paolo Cintia, Fedon Marcello Iaia, Javier Fernández and 1 more

    354 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0201264OpenAlex

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    Injuries have a great impact on professional soccer, due to their large influence on team performance and the considerable costs of rehabilitation for players. Existing studies in the literature provide just a preliminary understanding of which factors mostly affect injury risk, while an evaluation of the potential of statistical models in forecasting injuries is still missing. In this paper, we propose a multi-dimensional approach to injury forecasting in professional soccer that is based on GPS measurements and machine learning. By using GPS tracking technology, we collect data describing the training workload of players in a professional soccer club during a season. We then construct an injury forecaster and show that it is both accurate and interpretable by providing a set of case studies of interest to soccer practitioners. Our approach opens a novel perspective on injury prevention, providing a set of simple and practical rules for evaluating and interpreting the complex relations between injury risk and training performance in professional soccer.

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    Eye tracking cognitive load using pupil diameter and microsaccades with fixed gaze

    Krzysztof Krejtz, Andrew T. Duchowski, Anna Niedzielska, Cezary Biele, Izabela Krejtz

    352 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0203629OpenAlex

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    Pupil diameter and microsaccades are captured by an eye tracker and compared for their suitability as indicators of cognitive load (as beset by task difficulty). Specifically, two metrics are tested in response to task difficulty: (1) the change in pupil diameter with respect to inter- or intra-trial baseline, and (2) the rate and magnitude of microsaccades. Participants performed easy and difficult mental arithmetic tasks while fixating a central target. Inter-trial change in pupil diameter and microsaccade magnitude appear to adequately discriminate task difficulty, and hence cognitive load, if the implied causality can be assumed. This paper's contribution corroborates previous work concerning microsaccade magnitude and extends this work by directly comparing microsaccade metrics to pupillometric measures. To our knowledge this is the first study to compare the reliability and sensitivity of task-evoked pupillary and microsaccadic measures of cognitive load.

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    Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol

    Jingqiu Wang, Xianying Fang, Lin Ge, Fuliang Cao, Linguo Zhao and 2 more

    352 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0197563OpenAlex

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    Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells. A kae-induced increase in DPPH and ABTS radical scavenging activity, inhibition of concanavalin A (Con A)-induced activation of T cell proliferation and NO or ROS production in LPS-induced RAW 264.7 macrophage cells were also seen. Kae glycosides were used to produce kae via environment-friendly enzymatic hydrolysis. Kae-7-O-glu and kae-3-O-rut were hydrolyzed to kae by β-glucosidase and/or α-L-rhamnosidase. This paper demonstrates the application of enzymatic catalysis…

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    Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias

    Frederick Wolfe, Brian T. Walitt, Serge Perrot, Johannes Jacobus Rasker, Winfried Häuser

    346 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0203755OpenAlex

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    PURPOSE: Multiple clinical and epidemiological studies have provided estimates of fibromyalgia prevalence and sex ratio, but different criteria sets and methodology, as well as bias, have led to widely varying (0.4%->11%) estimates of prevalence and female predominance (>90% to <61%). In general, studies have failed to distinguish Criteria based fibromyalgia (CritFM) from Clinical fibromyalgia (ClinFM). In the current study we compare CritFM with ClinFM to investigate gender and other biases in the diagnosis of fibromyalgia. METHODS: We used a rheumatic disease databank and 2016 fibromyalgia criteria to study prevalence and sex ratios in a selection biased sample of 1761 referred and diagnosed fibromyalgia patients and in an unbiased sample of 4342 patients with no diagnosis with respect to fibromyalgia. We compared diagnostic and clinical variables according to gender, and we reanalyzed a German population study (GPS) (n = 2435) using revised 2016 criteria for fibromyalgia. RESULTS: In the selection-biased sample of referred patients with fibromyalgia, more than 90% were women.…

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    Questionable research practices in ecology and evolution

    Hannah S. Fraser, Tim Parker, Shinichi Nakagawa, Ashley Barnett, Fiona M. Fidler

    346 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200303OpenAlex

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    We surveyed 807 researchers (494 ecologists and 313 evolutionary biologists) about their use of Questionable Research Practices (QRPs), including cherry picking statistically significant results, p hacking, and hypothesising after the results are known (HARKing). We also asked them to estimate the proportion of their colleagues that use each of these QRPs. Several of the QRPs were prevalent within the ecology and evolution research community. Across the two groups, we found 64% of surveyed researchers reported they had at least once failed to report results because they were not statistically significant (cherry picking); 42% had collected more data after inspecting whether results were statistically significant (a form of p hacking) and 51% had reported an unexpected finding as though it had been hypothesised from the start (HARKing). Such practices have been directly implicated in the low rates of reproducible results uncovered by recent large scale replication studies in psychology and other disciplines. The rates of QRPs found in this study are comparable with the rates seen in…

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    Analysis of length of hospital stay using electronic health records: A statistical and data mining approach

    Hyunyoung Baek, Minsu Cho, Seok Kim, Hee Young Hwang, Minseok Song and 1 more

    346 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195901OpenAlex

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    BACKGROUND: The length of stay (LOS) is an important indicator of the efficiency of hospital management. Reduction in the number of inpatient days results in decreased risk of infection and medication side effects, improvement in the quality of treatment, and increased hospital profit with more efficient bed management. The purpose of this study was to determine which factors are associated with length of hospital stay, based on electronic health records, in order to manage hospital stay more efficiently. MATERIALS AND METHODS: Research subjects were retrieved from a database of patients admitted to a tertiary general university hospital in South Korea between January and December 2013. Patients were analyzed according to the following three categories: descriptive and exploratory analysis, process pattern analysis using process mining techniques, and statistical analysis and prediction of LOS. RESULTS: Overall, 55% (25,228) of inpatients were discharged within 4 days. The department of rehabilitation medicine (RH) had the highest average LOS at 15.9 days. Of all the conditions…

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    The unequal vulnerability of communities of color to wildfire

    Ian P. Davies, Ryan D. Haugo, James Craigie Robertson, Phillip S. Levin

    337 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0205825OpenAlex

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    Globally, environmental disasters impact billions of people and cost trillions of dollars in damage, and their impacts are often felt most acutely by minority and poor communities. Wildfires in the U.S. have similarly outsized impacts on vulnerable communities, though the ethnic and geographic distribution of those communities may be different than for other hazards. Here, we develop a social-ecological approach for characterizing fire vulnerability and apply it to >70,000 census tracts across the United States. Our approach incorporates both the wildfire potential of a landscape and socioeconomic attributes of overlying communities. We find that over 29 million Americans live with significant potential for extreme wildfires, a majority of whom are white and socioeconomically secure. Within this segment, however, are 12 million socially vulnerable Americans for whom a wildfire event could be devastating. Additionally, wildfire vulnerability is spread unequally across race and ethnicity, with census tracts that were majority Black, Hispanic or Native American experiencing ca. 50%…

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    Comparison of body composition assessment by DXA and BIA according to the body mass index: A retrospective study on 3655 measures

    Najate Achamrah, Guillaume Colange, Julie Delay, A. Rimbert, V. Folope and 4 more

    337 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200465OpenAlex

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    BACKGROUND AND AIMS: Body composition assessment is often used in clinical practice for nutritional evaluation and monitoring. The standard method, dual-energy X-ray absorptiometry (DXA), is hardly feasible in routine clinical practice contrary to Bioelectrical Impedance Analysis (BIA) method. We thus aimed to compare body composition assessment by DXA and BIA according to the body mass index (BMI) in a large cohort. METHODS: Retrospectively, we analysed DXA and BIA measures in patients followed in a Nutrition Unit from 2010 to 2016. Body composition was assessed under standardized conditions in the morning, after a fasting period of 12 h, by DXA (Lunar Prodigy Advance) and BIA (Bodystat QuadScan 4000, Manufacturer's equation). Bland-Altman test was performed for each class of BMI (kg/m2) and fat mass and fat free mass values were compared using Kruskal-Wallis test. Pearson correlations were also performed and the concordance coefficient of Lin was calculated. RESULTS: Whatever the BMI, BIA and DXA methods reported higher concordance for values of FM than FFM. Body composition…

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    Bias caused by sampling error in meta-analysis with small sample sizes

    Lifeng Lin

    336 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204056OpenAlex

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    BACKGROUND: Meta-analyses frequently include studies with small sample sizes. Researchers usually fail to account for sampling error in the reported within-study variances; they model the observed study-specific effect sizes with the within-study variances and treat these sample variances as if they were the true variances. However, this sampling error may be influential when sample sizes are small. This article illustrates that the sampling error may lead to substantial bias in meta-analysis results. METHODS: We conducted extensive simulation studies to assess the bias caused by sampling error. Meta-analyses with continuous and binary outcomes were simulated with various ranges of sample size and extents of heterogeneity. We evaluated the bias and the confidence interval coverage for five commonly-used effect sizes (i.e., the mean difference, standardized mean difference, odds ratio, risk ratio, and risk difference). RESULTS: Sampling error did not cause noticeable bias when the effect size was the mean difference, but the standardized mean difference, odds ratio, risk ratio, and…

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    Estimating genetic kin relationships in prehistoric populations

    José Manuel Monroy Kuhn, Mattias Jakobsson, Torsten Günther

    330 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195491OpenAlex

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    Archaeogenomic research has proven to be a valuable tool to trace migrations of historic and prehistoric individuals and groups, whereas relationships within a group or burial site have not been investigated to a large extent. Knowing the genetic kinship of historic and prehistoric individuals would give important insights into social structures of ancient and historic cultures. Most archaeogenetic research concerning kinship has been restricted to uniparental markers, while studies using genome-wide information were mainly focused on comparisons between populations. Applications which infer the degree of relationship based on modern-day DNA information typically require diploid genotype data. Low concentration of endogenous DNA, fragmentation and other post-mortem damage to ancient DNA (aDNA) makes the application of such tools unfeasible for most archaeological samples. To infer family relationships for degraded samples, we developed the software READ (Relationship Estimation from Ancient DNA). We show that our heuristic approach can successfully infer up to second degree…

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    More than a feeling: Autonomous sensory meridian response (ASMR) is characterized by reliable changes in affect and physiology

    Giulia Lara Poerio, Emma Blakey, Tom Hostler, Theresa Veltri

    329 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0196645OpenAlex

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    Autonomous Sensory Meridian Response (ASMR) describes the experience of tingling sensations in the crown of the head, in response to a range of audio-visual triggers such as whispering, tapping, and hand movements. Public interest in ASMR has risen dramatically and ASMR experiencers watch ASMR videos to promote relaxation and sleep. Unlike ostensibly similar emotional experiences such as "aesthetic chills" from music and awe-inspiring scenarios, the psychological basis of ASMR has not yet been established. We present two studies (one large-scale online experiment; one laboratory study) that test the emotional and physiological correlates of the ASMR response. Both studies showed that watching ASMR videos increased pleasant affect only in people who experienced ASMR. Study 2 showed that ASMR was associated with reduced heart rate and increased skin conductance levels. Findings indicate that ASMR is a reliable and physiologically-rooted experience that may have therapeutic benefits for mental and physical health.

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    Predicting hospital admission at emergency department triage using machine learning

    Woo Suk Hong, Adrian D. Haimovich, Richard Andrew Taylor

    325 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0201016OpenAlex

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    OBJECTIVE: To predict hospital admission at the time of ED triage using patient history in addition to information collected at triage. METHODS: This retrospective study included all adult ED visits between March 2014 and July 2017 from one academic and two community emergency rooms that resulted in either admission or discharge. A total of 972 variables were extracted per patient visit. Samples were randomly partitioned into training (80%), validation (10%), and test (10%) sets. We trained a series of nine binary classifiers using logistic regression (LR), gradient boosting (XGBoost), and deep neural networks (DNN) on three dataset types: one using only triage information, one using only patient history, and one using the full set of variables. Next, we tested the potential benefit of additional training samples by training models on increasing fractions of our data. Lastly, variables of importance were identified using information gain as a metric to create a low-dimensional model. RESULTS: A total of 560,486 patient visits were included in the study, with an overall admission…

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    The DREAMS core package of interventions: A comprehensive approach to preventing HIV among adolescent girls and young women

    Janet R. Saul, Gretchen L. Bachman, Shannon Allen, Nora Toiv, Caroline Cooney and 1 more

    321 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0208167OpenAlex

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    In sub-Saharan Africa, adolescent girls and young women (AGYW) are 5 to 14 times more likely to be infected with HIV than their male peers. Every day, more than 750 AGYW are infected with HIV. Many factors make girls and young women particularly vulnerable to HIV, including gender-based violence, exclusion from economic opportunities, and a lack of access to secondary school. The President's Emergency Plan for AIDS Relief (PEPFAR) is dedicating significant resources through the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) partnership to impact the lives of women and girls based on PEPFAR's mission to help countries achieve epidemic control of HIV/AIDS. The data show that new HIV infections must be reduced in AGYW, or the global community risks losing the extensive progress made towards reaching epidemic control. With support from PEPFAR and private sector partners-the Bill & Melinda Gates Foundation, Gilead Sciences, Girl Effect, Johnson & Johnson and ViiV Healthcare, DREAMS works together with partner governments to deliver a core package of…

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    Projecting shifts in thermal habitat for 686 species on the North American continental shelf

    James William Morley, Rebecca L. Selden, Robert J. Latour, Thomas Lukas Frölicher, Richard J. Seagraves and 1 more

    321 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0196127OpenAlex

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    Recent shifts in the geographic distribution of marine species have been linked to shifts in preferred thermal habitats. These shifts in distribution have already posed challenges for living marine resource management, and there is a strong need for projections of how species might be impacted by future changes in ocean temperatures during the 21st century. We modeled thermal habitat for 686 marine species in the Atlantic and Pacific oceans using long-term ecological survey data from the North American continental shelves. These habitat models were coupled to output from sixteen general circulation models that were run under high (RCP 8.5) and low (RCP 2.6) future greenhouse gas emission scenarios over the 21st century to produce 32 possible future outcomes for each species. The models generally agreed on the magnitude and direction of future shifts for some species (448 or 429 under RCP 8.5 and RCP 2.6, respectively), but strongly disagreed for other species (116 or 120 respectively). This allowed us to identify species with more or less robust predictions. Future shifts in species…

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    Video game loot boxes are linked to problem gambling: Results of a large-scale survey

    David I Zendle, Paul A. Cairns

    318 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0206767OpenAlex

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    Loot boxes are items in video games that can be paid for with real-world money and contain randomised contents. In recent years, loot boxes have become increasingly common. There is concern in the research community that similarities between loot boxes and gambling may lead to increases in problem gambling amongst gamers. A large-scale survey of gamers (n = 7,422) found evidence for a link (η2 = 0.054) between the amount that gamers spent on loot boxes and the severity of their problem gambling. This link was stronger than a link between problem gambling and buying other in-game items with real-world money (η2 = 0.004), suggesting that the gambling-like features of loot boxes are specifically responsible for the observed relationship between problem gambling and spending on loot boxes. It is unclear from this study whether buying loot boxes acts as a gateway to problem gambling, or whether spending large amounts of money on loot boxes appeals more to problem gamblers. However, in either case these results suggest that there may be good reason to regulate loot boxes in games.

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    Socio-economic determinants of physical activity across the life course: A "DEterminants of DIet and Physical ACtivity" (DEDIPAC) umbrella literature review

    Grainne O’Donoghue, Aileen Kennedy, Anna Puggina, Katina Aleksovska, Christoph Buck and 25 more

    311 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0190737OpenAlex

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    BACKGROUND: To date, the scientific literature on socioeconomic correlates and determinants of physical activity behaviours has been dispersed throughout a number of systematic reviews, often focusing on one factor (e.g. education or parental income) in one specific age group (e.g. pre-school children or adults). The aim of this umbrella review is to provide a comprehensive and systematic overview of the scientific literature from previously conducted research by summarising and synthesising the importance and strength of the evidence related to socioeconomic correlates and determinants of PA behaviours across the life course. METHODS: Medline, Embase, ISI Web of Science, Scopus and SPORTDiscus were searched for systematic literature reviews and meta-analyses of observational studies investigating the association between socioeconomic determinants of PA and PA itself (from January 2004 to September 2017). Data extraction evaluated the importance of determinants, strength of evidence, and methodological quality of the selected papers. The full protocol is available from PROSPERO…

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    Effects of microplastic exposure on the body condition and behaviour of planktivorous reef fish (Acanthochromis polyacanthus)

    Kay Critchell, Mia O. Hoogenboom

    310 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0193308OpenAlex

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    The effect of a pollutant on the base of the food web can have knock-on effects for trophic structure and ecosystem functioning. In this study we assess the effect of microplastic exposure on juveniles of a planktivorous fish (Acanthochromis polyacanthus), a species that is widespread and abundant on Indo-Pacific coral reefs. Under five different plastic concentration treatments, with plastics the same size as the natural food particles (mean 2mm diameter), there was no significant effect of plastic exposure on fish growth, body condition or behaviour. The amount of plastics found in the gastro-intestinal (GI) tract was low, with a range of one to eight particles remaining in the gut of individual fish at the end of a 6-week plastic-exposure period, suggesting that these fish are able to detect and avoid ingesting microplastics in this size range. However, in a second experiment the number of plastics in the GI tract vastly increased when plastic particle size was reduced to approximately one quarter the size of the food particles, with a maximum of 2102 small (< 300μm diameter)…

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    Disease-specific out-of-pocket and catastrophic health expenditure on hospitalization in India: Do Indian households face distress health financing?

    Anshul Kastor, Sanjay Kumar Mohanty

    309 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0196106OpenAlex

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    BACKGROUND: Rising non-communicable diseases (NCDs) coupled with increasing injuries have resulted in a significant increase in health spending in India. While out-of-pocket expenditure remains the major source of health care financing in India (two-thirds of the total health spending), the financial burden varies enormously across diseases and by the economic well-being of the households. Though prior studies have examined the variation in disease pattern, little is known about the financial risk to the families by type of diseases in India. In this context, the present study examines disease-specific out-of-pocket expenditure (OOPE), catastrophic health expenditure (CHE) and distress health financing. METHODS AND MATERIALS: Unit data from the 71st round of the National Sample Survey Organization (2014) was used for this study. OOPE is defined as health spending on hospitalization net of reimbursement, and CHE is defined as household health spending exceeding 10% of household consumption expenditure. Distress health financing is defined as a situation when a household has to borrow…

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    Patient navigators for people with chronic disease: A systematic review

    Kerry McBrien, Noah Michael Ivers, Lianne Barnieh, Jacob J. Bailey, Diane Lorenzetti and 7 more

    307 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191980OpenAlex

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    BACKGROUND: People with chronic diseases experience barriers to managing their diseases and accessing available health services. Patient navigator programs are increasingly being used to help people with chronic diseases navigate and access health services. OBJECTIVE: The objective of this review was to summarize the evidence for patient navigator programs in people with a broad range of chronic diseases, compared to usual care. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO, and Social Work Abstracts from inception to August 23, 2017. We also searched the reference lists of included articles. We included original reports of randomized controlled trials of patient navigator programs compared to usual care for adult and pediatric patients with any one of a defined set of chronic diseases. RESULTS: From a total of 14,672 abstracts, 67 unique studies fit our inclusion criteria. Of these, 44 were in cancer, 8 in diabetes, 7 in HIV/AIDS, 4 in cardiovascular disease, 2 in chronic kidney disease, 1 in dementia and 1 in patients with more than one condition. Program…

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    Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictus under changing climate

    Mahmoud Kamal, Mohamed Kenawy, Magda H. Rady, Amany Soliman Khaled, Abdallah M Samy

    303 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0210122OpenAlex

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    BACKGROUND: Aedes aegypti and Ae. albopictus are the primary vectors that transmit several arboviral diseases, including dengue, chikungunya, and Zika. The world is presently experiencing a series of outbreaks of these diseases, so, we still require to better understand the current distributions and possible future shifts of their vectors for successful surveillance and control programs. Few studies assessed the influences of climate change on the spatial distributional patterns and abundance of these important vectors, particularly using the most recent climatic scenarios. Here, we updated the current potential distributions of both vectors and assessed their distributional changes under future climate conditions. METHODS: We used ecological niche modeling approach to estimate the potential distributions of Ae. aegypti and Ae. albopictus under present-day and future climate conditions. This approach fits ecological niche model from occurrence records of each species and environmental variables. For each species, future projections were based on climatic data from 9 general…

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    Fast and inexpensive protocols for consistent extraction of high quality DNA and RNA from challenging plant and fungal samples for high-throughput SNP genotyping and sequencing applications

    Peter Ward Inglis, Marília de Castro Rodrigues Pappas, Lucileide Vilela Resende, Dario G. Grattapaglia

    302 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0206085OpenAlex

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    Modern genotyping techniques, such as SNP analysis and genotyping by sequencing (GBS), are hampered by poor DNA quality and purity, particularly in challenging plant species, rich in secondary metabolites. We therefore investigated the utility of a pre-wash step using a buffered sorbitol solution, prior to DNA extraction using a high salt CTAB extraction protocol, in a high throughput or miniprep setting. This pre-wash appears to remove interfering metabolites, such as polyphenols and polysaccharides, from tissue macerates. We also investigated the adaptability of the sorbitol pre-wash for RNA extraction using a lithium chloride-based protocol. The method was successfully applied to a variety of tissues, including leaf, cambium and fruit of diverse plant species including annual crops, forest and fruit trees, herbarium leaf material and lyophilized fungal mycelium. We consistently obtained good yields of high purity DNA or RNA in all species tested. The protocol has been validated for thousands of DNA samples by generating high data quality in dense SNP arrays. DNA extracted from…

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    Deep neural networks show an equivalent and often superior performance to dermatologists in onychomycosis diagnosis: Automatic construction of onychomycosis datasets by region-based convolutional deep neural network

    Seung Seog Han, Gyeong‐Hun Park, Woohyung Lim, Myoung Shin Kim, Jung‐Im Na and 2 more

    302 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191493OpenAlex

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    Although there have been reports of the successful diagnosis of skin disorders using deep learning, unrealistically large clinical image datasets are required for artificial intelligence (AI) training. We created datasets of standardized nail images using a region-based convolutional neural network (R-CNN) trained to distinguish the nail from the background. We used R-CNN to generate training datasets of 49,567 images, which we then used to fine-tune the ResNet-152 and VGG-19 models. The validation datasets comprised 100 and 194 images from Inje University (B1 and B2 datasets, respectively), 125 images from Hallym University (C dataset), and 939 images from Seoul National University (D dataset). The AI (ensemble model; ResNet-152 + VGG-19 + feedforward neural networks) results showed test sensitivity/specificity/ area under the curve values of (96.0 / 94.7 / 0.98), (82.7 / 96.7 / 0.95), (92.3 / 79.3 / 0.93), (87.7 / 69.3 / 0.82) for the B1, B2, C, and D datasets. With a combination of the B1 and C datasets, the AI Youden index was significantly (p = 0.01) higher than that of 42…

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    Can species distribution models really predict the expansion of invasive species?

    Morgane Barbet‐Massin, Quentin Rome, Claire Villemant, Franck Courchamp

    296 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0193085OpenAlex

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    Predictive studies are of paramount importance for biological invasions, one of the biggest threats for biodiversity. To help and better prioritize management strategies, species distribution models (SDMs) are often used to predict the potential invasive range of introduced species. Yet, SDMs have been regularly criticized, due to several strong limitations, such as violating the equilibrium assumption during the invasion process. Unfortunately, validation studies-with independent data-are too scarce to assess the predictive accuracy of SDMs in invasion biology. Yet, biological invasions allow to test SDMs usefulness, by retrospectively assessing whether they would have accurately predicted the latest ranges of invasion. Here, we assess the predictive accuracy of SDMs in predicting the expansion of invasive species. We used temporal occurrence data for the Asian hornet Vespa velutina nigrithorax, a species native to China that is invading Europe with a very fast rate. Specifically, we compared occurrence data from the last stage of invasion (independent validation points) to the…

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    Reduced microbiome alpha diversity in young patients with ADHD

    Alexander Prehn‐Kristensen, Alexandra Zimmermann, Lukas Tittmann, Wolfgang Lieb, Stefan Schreiber and 2 more

    295 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200728OpenAlex

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    ADHD is a psychiatric disorder which is characterized by hyperactivity, impulsivity and attention problems. Due to recent findings of microbial involvement in other psychiatric disorders like autism and depression, a role of the gut microbiota in ADHD pathogenesis is assumed but has not yet been investigated. In this study, the gut microbiota of 14 male ADHD patients (mean age: 11.9 yrs.) and 17 male controls (mean age: 13.1 yrs.) was examined via next generation sequencing of 16S rDNA and analyzed for diversity and biomarkers. We found that the microbial diversity (alpha diversity) was significantly decreased in ADHD patients compared to controls (pShannon = 0.036) and that the composition (beta diversity) differed significantly between patients and controls (pANOSIM = 0.033, pADONIS = 0.006, pbetadisper = 0.002). In detail, the bacterial family Prevotellacae was associated with controls, while patients with ADHD showed elevated levels of Bacteroidaceae, and both Neisseriaceae and Neisseria spec. were found as possible biomarkers for juvenile ADHD. Our results point to a possible…

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    Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis

    Siddharth Singh, Antonio Facciorusso, Abha Goyal Singh, Niels Vande Casteele, Amir Zarrinpar and 4 more

    294 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195123OpenAlex

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    OBJECTIVES: We sought to evaluate the association between obesity and response to anti-tumor necrosis factor-α (TNF) agents, through a systematic review and meta-analysis. METHODS: Through a systematic search through January 24, 2017, we identified randomized controlled trials (RCTs) or observational studies in adults with select immune-mediated inflammatory diseases-inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathies (SpA), psoriasis and psoriatic arthritis (PsA)-treated with anti-TNF agents, and reporting outcomes, stratified by body mass index (BMI) categories or weight. Primary outcome was failure to achieve clinical remission or response or treatment modification. We performed random effects meta-analysis and estimated odds ratios (OR) and 95% confidence interval (CI). RESULTS: Based on 54 cohorts including 19,372 patients (23% obese), patients with obesity had 60% higher odds of failing therapy (OR,1.60; 95% CI,1.39-1.83;I2 = 71%). Dose-response relationship was observed (obese vs. normal BMI: OR,1.87 [1.39-2.52]; overweight vs. normal BMI:…

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    Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments

    Ryan S. Noyce, Seth M. Lederman, David H. Evans

    294 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0188453OpenAlex

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    Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, we explored whether HPXV could be obtained by large-scale gene synthesis. Ten large (10-30 kb) fragments of DNA were synthesized based on the HPXV sequence along with two 157 nt VACV terminal sequences, and were recombined into a live synthetic chimeric HPXV (scHPXV) in cells infected with Shope fibroma virus (SFV). Sequencing of the 212 kbp scHPXV confirmed it encoded a faithful copy of the input DNA. We believe this is the first complete synthesis of a poxvirus using synthetic biology approaches. This scHPXV produced smaller plaques, produced less extracellular virus and exhibited less virulence in mice than VACV, but…

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    Development, characterization and comparisons of targeted and non-targeted metabolomics methods

    Anton Ribbenstedt, Haizea Ziarrusta, Jonathan P. Benskin

    290 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0207082OpenAlex

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    The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision, unequivocal identification, and broad metabolomic coverage. While the former two metrics are usually associated with targeted metabolomics and the latter with non-targeted metabolomics, a systematic comparison of the performance of both approaches has not yet been carried out. The present work reports on the development and performance evaluation of separate targeted and non-targeted metabolomics methods. The targeted approach facilitated determination of 181 metabolites (quantitative analysis of 18 amino acids, 11 biogenic amines, 5 neurotransmitters, 5 nucleobases and semi-quantitative analysis of 50 carnitines, 83 phosphatidylcholines, and 9 sphingomyelins) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and flow injection-tandem mass spectrometry (FI-MS/MS). Method accuracy and/or precision were assessed using replicate samples of NIST SRM1950 as well as fish liver and brain…

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    Global and regional trends of people living with HIV aged 50 and over: Estimates and projections for 2000–2020

    Christine S. Autenrieth, Eduard J. Beck, Dominik Stelzle, Christoforos Mallouris, Mary I. Mahy and 1 more

    287 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0207005OpenAlex

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    BACKGROUND: The increasing numbers of people living with HIV (PLHIV) who are receiving antiretroviral therapy (ART) have near normal life-expectancy, resulting in more people living with HIV over the age of 50 years (PLHIV50+). Estimates of the number of PLHIV50+ are needed for the development of tailored therapeutic and prevention interventions at country, regional and global level. METHODS: The AIDS Impact Module of the Spectrum software was used to compute the numbers of PLHIV, new infections, and AIDS-related deaths for PLHIV50+ for the years 2000-2016. Projections until 2020 were calculated based on an assumed ART scale-up to 81% coverage by 2020, consistent with the UNAIDS 90-90-90 treatment targets. RESULTS: Globally, there were 5.7 million [4.7 million- 6.6 million] PLHIV50+ in 2016. The proportion of PLHIV50+ increased substantially from 8% in 2000 to 16% in 2016 and is expected to increase to 21% by 2020. In 2016, 80% of PLHIV50+ lived in low- and middle-income countries (LMICs), with Eastern and Southern Africa containing the largest number of PLHIV50+. While the…

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    Global etiology of bacterial meningitis: A systematic review and meta-analysis

    Anouk M. Oordt-Speets, Renee Bolijn, Rosa C. van Hoorn, Amit B. Bhavsar, Moe Hein Kyaw

    287 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0198772OpenAlex

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    Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the…

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    Patient and public engagement in priority setting: A systematic rapid review of the literature

    Elizabeth Manafò, Lisa Petermann, Virginia Vandall‐Walker, Ping Mason-Lai

    286 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0193579OpenAlex

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    BACKGROUND: Current research suggests that while patients are becoming more engaged across the health delivery spectrum, this involvement occurs most often at the pre-preparation stage to identify 'high-level' priorities in health ecosystem priority setting, and at the preparation phase for health research. OBJECTIVE: The purpose of this systematic rapid review of the literature is to describe the evidence that does exist in relation to patient and public engagement priority setting in both health ecosystem and health research. DATA SOURCES: HealthStar (via OVID); CINAHL; Proquest Databases; and Scholar's Portal. STUDY ELIGIBILITY CRITERIA: i) published in English; ii) published within the timeframe of 2007-Current (10 years) unless the report/article was formative in synthesizing key considerations of patient engagement in health ecosystem and health research priority setting; iii) conducted in Canada, the US, Europe, UK, Australia/New Zealand, or Scandinavian countries. STUDY APPRAISAL AND SYNTHESIS: i) Is the research valid, sound, and applicable?; ii) what outcomes can we…

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    Stroke survivors' and informal caregivers' experiences of primary care and community healthcare services – A systematic review and meta-ethnography

    Dominika M. Pindus, Ricky Mullis, Lisa Lim, Ian Wellwood, A. Viona Rundell and 2 more

    284 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0192533OpenAlex

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    OBJECTIVE: To describe and explain stroke survivors and informal caregivers' experiences of primary care and community healthcare services. To offer potential solutions for how negative experiences could be addressed by healthcare services. DESIGN: Systematic review and meta-ethnography. DATA SOURCES: Medline, CINAHL, Embase and PsycINFO databases (literature searched until May 2015, published studies ranged from 1996 to 2015). ELIGIBILITY CRITERIA: Primary qualitative studies focused on adult community-dwelling stroke survivors' and/or informal caregivers' experiences of primary care and/or community healthcare services. DATA SYNTHESIS: A set of common second order constructs (original authors' interpretations of participants' experiences) were identified across the studies and used to develop a novel integrative account of the data (third order constructs). Study quality was assessed using the Critical Appraisal Skills Programme checklist. Relevance was assessed using Dixon-Woods' criteria. RESULTS: 51 studies (including 168 stroke survivors and 328 caregivers) were synthesised.…

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    So many genes, so little time: A practical approach to divergence-time estimation in the genomic era

    Stephen A. Smith, Joseph W. Brown, Joseph F. Walker

    282 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0197433OpenAlex

    Show abstract

    Phylogenomic datasets have been successfully used to address questions involving evolutionary relationships, patterns of genome structure, signatures of selection, and gene and genome duplications. However, despite the recent explosion in genomic and transcriptomic data, the utility of these data sources for efficient divergence-time inference remains unexamined. Phylogenomic datasets pose two distinct problems for divergence-time estimation: (i) the volume of data makes inference of the entire dataset intractable, and (ii) the extent of underlying topological and rate heterogeneity across genes makes model mis-specification a real concern. "Gene shopping", wherein a phylogenomic dataset is winnowed to a set of genes with desirable properties, represents an alternative approach that holds promise in alleviating these issues. We implemented an approach for phylogenomic datasets (available in SortaDate) that filters genes by three criteria: (i) clock-likeness, (ii) reasonable tree length (i.e., discernible information content), and (iii) least topological conflict with a focal species…

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    Anatomy of an online misinformation network

    Chengcheng Shao, Pik-Mai Hui, Lei Wang, Xinwen Jiang, Alessandro Flammini and 2 more

    282 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0196087OpenAlex

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    Massive amounts of fake news and conspiratorial content have spread over social media before and after the 2016 US Presidential Elections despite intense fact-checking efforts. How do the spread of misinformation and fact-checking compete? What are the structural and dynamic characteristics of the core of the misinformation diffusion network, and who are its main purveyors? How to reduce the overall amount of misinformation? To explore these questions we built Hoaxy, an open platform that enables large-scale, systematic studies of how misinformation and fact-checking spread and compete on Twitter. Hoaxy captures public tweets that include links to articles from low-credibility and fact-checking sources. We perform k-core decomposition on a diffusion network obtained from two million retweets produced by several hundred thousand accounts over the six months before the election. As we move from the periphery to the core of the network, fact-checking nearly disappears, while social bots proliferate. The number of users in the main core reaches equilibrium around the time of the…

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    Automated measurement of fetal head circumference using 2D ultrasound images

    Thomas L. A. van den Heuvel, Dagmar de Bruijn, Chris L. de Korte, Bram van Ginneken

    280 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200412OpenAlex

    Show abstract

    In this paper we present a computer aided detection (CAD) system for automated measurement of the fetal head circumference (HC) in 2D ultrasound images for all trimesters of the pregnancy. The HC can be used to estimate the gestational age and monitor growth of the fetus. Automated HC assessment could be valuable in developing countries, where there is a severe shortage of trained sonographers. The CAD system consists of two steps: First, Haar-like features were computed from the ultrasound images to train a random forest classifier to locate the fetal skull. Secondly, the HC was extracted using Hough transform, dynamic programming and an ellipse fit. The CAD system was trained on 999 images and validated on an independent test set of 335 images from all trimesters. The test set was manually annotated by an experienced sonographer and a medical researcher. The reference gestational age (GA) was estimated using the crown-rump length measurement (CRL). The mean difference between the reference GA and the GA estimated by the experienced sonographer was 0.8 ± 2.6, -0.0 ± 4.6 and 1.9 ±…

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    Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance

    Albert M. Isaacs, Jay K. Riva-Cambrin, Daniel Yavin, Aaron Hockley, Tamara Milka Pringsheim and 5 more

    279 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204926OpenAlex

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    BACKGROUND: Hydrocephalus is a debilitating disorder, affecting all age groups. Evaluation of its global epidemiology is required for healthcare planning and resource allocation. OBJECTIVES: To define age-specific global prevalence and incidence of hydrocephalus. METHODS: Population-based studies reporting prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text articles and abstracted data. Metanalysis and meta-regressions were used to assess associations between key variables. Heterogeneity and publication bias were assessed. Main outcome of interest was hydrocephalus prevalence among pediatric (≤ 18 years), adults (19-64 years), and elderly (≥ 65) patients. Annual hydrocephalus incidence stratified by country income level and folate fortification requirements were obtained (2003-2014) from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). RESULTS: Of 2,460…

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    On the overestimation of random forest’s out-of-bag error

    Silke Janitza, Roman Hornung

    279 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0201904OpenAlex

    Show abstract

    The ensemble method random forests has become a popular classification tool in bioinformatics and related fields. The out-of-bag error is an error estimation technique often used to evaluate the accuracy of a random forest and to select appropriate values for tuning parameters, such as the number of candidate predictors that are randomly drawn for a split, referred to as mtry. However, for binary classification problems with metric predictors it has been shown that the out-of-bag error can overestimate the true prediction error depending on the choices of random forests parameters. Based on simulated and real data this paper aims to identify settings for which this overestimation is likely. It is, moreover, questionable whether the out-of-bag error can be used in classification tasks for selecting tuning parameters like mtry, because the overestimation is seen to depend on the parameter mtry. The simulation-based and real-data based studies with metric predictor variables performed in this paper show that the overestimation is largest in balanced settings and in settings with few…

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    Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly

    Kathrin Rehfeld, Angie Lüders, Anita Hökelmann, Volkmar Leßmann, Joern Kaufmann and 3 more

    275 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0196636OpenAlex

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    Animal research indicates that a combination of physical activity and sensory enrichment has the largest and the only sustaining effect on adult neuroplasticity. Dancing has been suggested as a human homologue to this combined intervention as it poses demands on both physical and cognitive functions. For the present exploratory study, we designed an especially challenging dance program in which our elderly participants constantly had to learn novel and increasingly difficult choreographies. This six-month-long program was compared to conventional fitness training matched for intensity. An extensive pre/post-assessment was performed on the 38 participants (63-80 y), covering general cognition, attention, memory, postural and cardio-respiratory performance, neurotrophic factors and-most crucially-structural MRI using an exploratory analysis. For analysis of MRI data, a new method of voxel-based morphometry (VBM) designed specifically for pairwise longitudinal group comparisons was employed. Both interventions increased physical fitness to the same extent. Pronounced differences were…

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    Gender-transformative Bandebereho couples’ intervention to promote male engagement in reproductive and maternal health and violence prevention in Rwanda: Findings from a randomized controlled trial

    Kate Doyle, Ruti Levtov, Gary Barker, Gautam Gustav Bastian, Jeffrey B. Bingenheimer and 6 more

    275 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0192756OpenAlex

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    BACKGROUND: Rigorous evidence of the effectiveness of male engagement interventions, particularly on how these interventions impact relationship power dynamics and women's decision-making, remains limited. This study assessed the impact of the Bandebereho gender-transformative couples' intervention on impact on multiple behavioral and health-related outcomes influenced by gender norms and power relations. METHODS: We conducted a multi-site randomised controlled trial in four Rwandan districts with expectant/current fathers and their partners, who were randomised to the intervention (n = 575 couples) or control group (n = 624 couples). Primary outcomes include women's experience of physical and sexual IPV, women's attendance and men's accompaniment at ANC, modern contraceptive use, and partner support during pregnancy. At 21-months post-baseline, 1123 men and 1162 partners were included in intention to treat analysis. Generalized estimating equations with robust standard errors were used to fit the models. FINDINGS: The Bandebereho intervention led to substantial improvements in…

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    Comparing the cost effectiveness of nature-based and coastal adaptation: A case study from the Gulf Coast of the United States

    Borja G. Reguero, Michael W. Beck, David Niklaus Bresch, Juliano Calil, Imèn Meliane

    271 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0192132OpenAlex

    Show abstract

    Coastal risks are increasing from both development and climate change. Interest is growing in the protective role that coastal nature-based measures (or green infrastructure), such as reefs and wetlands, can play in adapting to these risks. However, a lack of quantitative information on their relative costs and benefits is one principal factor limiting their use more broadly. Here, we apply a quantitative risk assessment framework to assess coastal flood risk (from climate change and economic exposure growth) across the United States Gulf of Mexico coast to compare the cost effectiveness of different adaptation measures. These include nature-based (e.g. oyster reef restoration), structural or grey (e.g., seawalls) and policy measures (e.g. home elevation). We first find that coastal development will be a critical driver of risk, particularly for major disasters, but climate change will cause more recurrent losses through changes in storms and relative sea level rise. By 2030, flooding will cost $134-176.6 billion (for different economic growth scenarios), but as the effects of…

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    Social support and subjective burden in caregivers of adults and older adults: A meta-analysis

    Rafael del Pino Casado, Antonio Frías Osuna, Pedro Ángel Palomino Moral, María Ruzafa‐Martínez, Antonio Jesús Ramos‐Morcillo

    271 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0189874OpenAlex

    Show abstract

    BACKGROUND: Despite the generally accepted belief that social support improves caregiver adjustment in general and subjective burden in particular, the literature shows mixed findings, and a recent review concluded that the predictive strength of caregiver social support in determining caregiver burden is less evident, due to the conceptual diversity of this determinant. OBJECTIVE: The purpose of this review is to analyse the relationship of perceived and received social support with subjective burden among informal caregivers of an adult or older adult. METHODS: A systematic search was carried out up to September 2017 in the following databases: MEDLINE (PubMed), CINAHL, EMBASE, PsycINFO), Scopus and ISI Proceedings, and a meta-analysis was performed with the results of the selected and included studies. RESULTS: Fifty-six studies were included in the meta-analysis, which provided 46 independent comparisons for perceived support and 16 for received support. Most of these studies were cross-sectional. There was a moderate, negative association of perceived social support on…

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    The prevalence and trends of waterpipe tobacco smoking: A systematic review

    Mohammed Jawad, Rana Charide, Reem Waziry, Andrea J. Darzi, Rami A. Ballout and 1 more

    270 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0192191OpenAlex

    Show abstract

    INTRODUCTION: Waterpipe tobacco smoking is harmful to health however its prevalence estimates remain uncertain. We aimed to systematically review the medical literature on waterpipe tobacco prevalence and trends. METHODS: We searched Medline, Embase and ISI Web of Science for 'waterpipe' and its synonyms, without using language or date restrictions. We included any measure of waterpipe tobacco smoking prevalence in jurisdictionally representative populations. We stratified findings by prevalence measure (past 30 day, ever, regular or occasional, daily, other or unspecified) and age (adults or youth). RESULTS: We included 129 studies reporting 355 estimates for 68 countries. In general, prevalence estimates among adults were highest in the Eastern Mediterranean, and among youth were about equal between Eastern Mediterranean and European regions. Past 30 day use was highest among Lebanese youth (37.2% in 2008), ever use was highest among Lebanese youth in 2002 and Lebanese university students in 2005 (both 65.3%), regular or occasional use was highest in among Iranian university…

  87. 87
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    Virtual reality perspective-taking increases cognitive empathy for specific others

    Austin van Loon, Jeremy N. Bailenson, Jamil Zaki, Joshua Bostick, Robb Willer

    267 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0202442OpenAlex

    Show abstract

    Previous research shows that virtual reality perspective-taking experiences (VRPT) can increase prosocial behavior toward others. We extend this research by exploring whether this effect of VRPT is driven by increased empathy and whether the effect extends to ostensibly real-stakes behavioral games. In a pre-registered laboratory experiment (N = 180), participants interacted with an ostensible partner (a student from the same university as them) on a series of real-stakes economic games after (a) taking the perspective of the partner in a virtual reality, "day-in-the-life" simulation, (b) taking the perspective of a different person in a "day-in-the-life" simulation, or (c) doing a neutral activity in a virtual environment. The VRPT experience successfully increased participants' subsequent propensity to take the perspective of their partner (a facet of empathy), but only if the partner was the same person whose perspective participants assumed in the virtual reality simulation. Further, this effect of VRPT on perspective-taking was moderated by participants' reported feeling of…

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    Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis

    Agneta H. Fischer, Mariska Esther Kret, Joost Broekens

    266 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0190712OpenAlex

    Show abstract

    Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of…

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    Choosing an appropriate probiotic product for your patient: An evidence-based practical guide

    Jason C. Sniffen, Lynne Vernice McFarland, Charlesnika Tyon Evans, Ellie J. C. Goldstein

    265 citationsOpen access (PUBLIC-DOMAIN)doi:10.1371/journal.pone.0209205OpenAlex

    Show abstract

    INTRODUCTION: Clinicians and patients face a daunting task when choosing the most appropriate probiotic for their specific needs. Available preparations encompass a diverse and continuously expanding product base, with most available products lacking evidence-based trials that support their use. Even when evidence exists, not all probiotic products are equally effective for all disease prevention or treatment indications. At this point in time, drug regulatory agencies offer limited assistance with regard to guidance and oversight in most countries, including the U.S. METHODS: We reviewed the current medical literature and sources on the internet to survey the types of available probiotic products and to determine which probiotics had evidence-based efficacy data. Standard medical databases from inception to June 2018 were searched and discussions with experts in the field were conducted. We graded the strength of the evidence for probiotics having multiple, randomized controlled trials and developed a guide for the practical selection of current probiotic products for specific…

  90. 90
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    Identification of RNA-binding proteins in exosomes capable of interacting with different types of RNA: RBP-facilitated transport of RNAs into exosomes

    Luisa Statello, Marco Maugeri, Elena Garré, Muhammad Nawaz, Jessica Wahlgren and 10 more

    262 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195969OpenAlex

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    The RNA that is packaged into exosomes is termed as exosomal-shuttle RNA (esRNA); however, the players, which take this subset of RNA (esRNA) into exosomes, remain largely unknown. We hypothesized that RNA binding proteins (RBPs) could serve as key players in this mechanism, by making complexes with RNAs and transporting them into exosomes during the biosynthesis of exosomes. Here, we demonstrate the presence of 30 RBPs in exosomes that were shown to form RNA-RBP complexes with both cellular RNA and exosomal-RNA species. To assess the involvement of these RBPs in RNA-transfer into exosomes, the gene transcripts encoding six of the proteins identified in exosomes (HSP90AB1, XPO5, hnRNPH1, hnRNPM, hnRNPA2B1, and MVP) were silenced by siRNA and subsequent effect on esRNA was assessed. A significant reduction of total esRNA was observed by post-transcriptional silencing of MVP, compared to other RBPs. Furthermore, to confirm the binding of MVP with esRNA, a biotinylated-MVP was transiently expressed in HEK293F cells. Higher levels of esRNA were recovered from MVP that was eluted from…

  91. 91
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    Declining racial and ethnic representation in clinical academic medicine: A longitudinal study of 16 US medical specialties

    Elle Lett, Whitney U. Orji, Ronnie Sebro

    260 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0207274OpenAlex

    Show abstract

    OBJECTIVE: To evaluate trends in racial, ethnic, and sex representation at US medical schools across 16 specialties: internal medicine, pediatrics, surgery, psychiatry, radiology, anesthesiology, obstetrics and gynecology, neurology, family practice, pathology, emergency medicine, orthopedic surgery, ophthalmology, otolaryngology, physical medicine and rehabilitation, and dermatology. Using a novel, Census-derived statistical measure of diversity, the S-score, we quantified the degree of underrepresentation for racial minority groups and female faculty by rank for assistant, associate, and full professors from 1990-2016. METHODS: This longitudinal study of faculty diversity uses data obtained from the American Association of Medical Colleges (AAMC) Faculty Roster from US allopathic medical schools. The proportion of professors of racial minority groups and female faculty by rank was compared to the US population based on data from the US Census Bureau. The Roster includes data on 52,939 clinical medical faculty in 1990, and 129,545 in 2016, at the assistant professor level or…

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    Nighttime lights as a proxy for human development at the local level

    Anna Bruederle, Roland Hodler

    259 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0202231OpenAlex

    Show abstract

    Nighttime lights, calculated from weather satellite recordings, are increasingly used by social scientists as a proxy for economic activity or economic development in subnational regions of developing countries where disaggregated data from statistical offices are not available. However, so far, our understanding of what nighttime lights capture in these countries is limited. We use geo-referenced Demographic and Health Surveys (DHS) from 29 African countries to construct indicators of household wealth, education and health for DHS cluster locations as well as for grid cells of roughly 50 × 50 km. We show that nighttime lights are positively associated with these location-specific indicators of human development, and that the variation in nighttime lights can explain a substantial share in the variation in these indicators. We conclude that nighttime lights are a good proxy for human development at the local level.

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    VEGF may contribute to macrophage recruitment and M2 polarization in the decidua

    Karen C. Wheeler, Manoj K. Jena, Bhola Shankar Pradhan, Neha Nayak, Subhendu Das and 4 more

    258 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0191040OpenAlex

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    It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the…

  94. 94
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    Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid

    Samantha Yuille, Nicole Reichardt, Suchita Panda, Hayley Dunbar, Imke E. Mulder

    257 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0201073OpenAlex

    Show abstract

    Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric…

  95. 95
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    Metabolic equivalent of task (METs) thresholds as an indicator of physical activity intensity

    Márcio de Almeida Mendes, Inácio Crochemore‐Silva, Virgílio Viana Ramires, Felipe Fossati Reichert, Rafaela Costa Martins and 2 more

    256 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0200701OpenAlex

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    The purpose of the study was to identify and compare validity parameters of different absolute intensity thresholds in METs, using relative intensity classification as criterion measure. Convenience sampling was used to recruit total of 112 adults. The participants carried out an incremental maximal cycle ergometer test and asked to perform nine free-living activities. The oxygen uptake was measured by a VO2000® gas analyser throughout the tests. The intensity thresholds were identified using Receiver Operator Characteristic (ROC) curve analysis, having relative intensity categories as criterion measure. A total of 103 participants attended the two visits. Among 54 men and 49 women, the mean (± SD) ages were 36.1 (± 11.1) and 33.9 (± 10.6) years, respectively. The intensity thresholds identified were 4.9 METs for moderate and 6.8 METs for vigorous physical activity. In conclusion, the physical activity thresholds, generated according to the entire sample, were higher and presented improved specificity when compared to thresholds currently recommended. Moreover, these parameters…

  96. 96
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    Fear of falling in community-dwelling older adults: A cause of falls, a consequence, or both?

    Ana Lavedán, Maria Viladrosa, Pilar Jürschik, Teresa Botigué, Carmen Nuín and 2 more

    256 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194967OpenAlex

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    BACKGROUND: Despite the number of studies that have tried to demonstrate that there is an association between previous falls and the fear of falling, the relationship between these two variables remains a matter of controversy. OBJECTIVES: Our objective was to investigate whether the fear of falling is a cause of falls, a consequence, or both in community-dwelling adults aged ≥ 75 years old. METHODS: A descriptive, longitudinal, prospective study was performed. A total of 640 individuals were interviewed between 2009 and 2011. Sociodemographic data, health status, history of falls and fear of falling were assessed at baseline and at 24 months. RESULTS: The prevalence of falls at baseline was 25% as opposed to 35.2% at 24 months. The prevalence of the fear of falling was 41.5% at baseline. Logistic regression analysis showed a significant association between a history of falls and the fear of falling. Other factors associated with the fear of falling were female gender, comorbidity, depressive symptoms, and disability. In total, 41.7% of the subjects who had reported a fear of…

  97. 97
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    Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis

    Rupert Major, Mark R. I. Cheng, Robert A. Grant, Saran Shantikumar, Gang Xu and 3 more

    254 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0192895OpenAlex

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    BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is a global health burden and is independently associated with increased cardiovascular disease risk. Assessment of cardiovascular risk in the general population using prognostic models based on routinely collected risk factors is embedded in clinical practice. In CKD, prognostic models may misrepresent risk due to the interplay of traditional atherosclerotic and non-traditional risk factors. This systematic review's aim was to identify routinely collected risk factors for inclusion in a CKD-specific cardiovascular prognostic model. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Systematic review and meta-analysis of observational cohort studies and randomized controlled trials. Studies identified from MEDLINE and Embase searches using a pre-defined and registered protocol (PROSPERO ID-2016:CRD42016036187). The main inclusion criteria were individuals ≥18 years of age with non-endstage CKD. Routinely collected risk factors where multi-variable adjustment for established cardiovascular risk factors had occurred were extracted.…

  98. 98
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    Phosphate solubilizing bacteria with glucose dehydrogenase gene for phosphorus uptake and beneficial effects on wheat

    Muhammad Suleman, Sumera Yasmin, Maria Rasul, Mahreen Yahya, Babar Manzoor Atta and 1 more

    253 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0204408OpenAlex

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    The aim of this study was to isolate, characterize and use phosphate solubilizing bacteria to enhance the bioavailability of insoluble Ca-phosphate for wheat plants. For this purpose, 15 phosphorus solubilizing bacteria (PSB) were isolated from wheat rhizospheric soils of Peshawar and southern Punjab region, Pakistan. These isolates were identified using light microscopy and 16S rRNA gene. Among the isolated bacteria, two strains (Pseudomonas sp. MS16 and Enterobacter sp. MS32) were the efficient P solubilizers based on their P solubilization activity determined qualitatively (solubilization index 3.2-5.8) as well as quantitatively (136-280 μg mL-1). These two strains produced indole-3-acetic acid (25.6-28.1 μg mL-1), gibberellic acid (2.5-11.8), solubilized zinc compounds (SI 2.8-3.3) and showed nitrogenase and 1-Aminocyclopropane-1-carboxylic acid deaminase activity in vitro. Phosphate solubilization activity of Pseudomonas sp. MS16 was further validated by amplification, sequencing and phylogenetic analysis of glucose dehydrogenase (gcd) gene (LT908484) responsible for P…

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    Niosomes, an alternative for liposomal delivery

    Rianne Bartelds, Mohammad Hadi Nematollahi, Tjeerd Pols, Marc C. A. Stuart, Abbas Pardakhty and 2 more

    252 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0194179OpenAlex

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    Niosomes are used in studies for drug delivery or gene transfer. However, their physical properties and features relative to liposomes are not well documented. To characterize and more rationally optimize niosome formulations, the properties of these vesicle systems are compared to those of liposomes composed of phosphatidylcholine and phosphatidylethanolamine lipids plus cholesterol. Niosomes are highly stable and only slightly more leaky than liposomes as assayed by calcein leakage; the permeability for ions (KCl) is higher than that of liposomes. Contrary to liposomes, the size of niosomes decreases substantially upon freezing in liquid nitrogen and subsequent thawing, as shown by cryo-EM and dynamic light scattering. The packing of niosomal membranes was determined by laurdan fluorescence and is slightly lower than that of liposomes. We did not succeed in the functional reconstitution of the L-arginine/L-ornithine antiporter ArcD2 in niosomes, which we attribute to the non-ionic nature of the surfactants. The antimicrobial peptides alamethicin and melittin act similarly on…

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    Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody with extended duration of action

    Douglas L. Sheridan, Zhao-Xue Yu, Yuchun Zhang, Rekha Patel, Fang Zhen Sun and 6 more

    252 citationsOpen access (CC-BY)doi:10.1371/journal.pone.0195909OpenAlex

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    Eculizumab, a monoclonal antibody (mAb) directed against complement protein C5, is considered to be the current standard of care for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. This study describes the generation and preclinical attributes of ALXN1210, a new long-acting anti-C5 mAb, obtained through select modifications to eculizumab to both largely abolish target-mediated drug disposition (TMDD) and increase recycling efficiency via the neonatal Fc receptor (FcRn). To attenuate the effect of TMDD on plasma terminal half-life (t1/2), histidine substitutions were engineered into the complementarity-determining regions of eculizumab to enhance the dissociation rate of the mAb:C5 complex in the acidic early endosome relative to the slightly basic pH of blood. Antibody variants with optimal pH-dependent binding to C5 exhibited little to no TMDD in mice in the presence of human C5. To further enhance the efficiency of FcRn-mediated recycling of the antibody, two additional substitutions were introduced to increase affinity for human…

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The cohort is every article, review and book chapter OpenAlex attributes to PLoS ONE with publication year 2018, excluding retracted works and paratext such as editorials and errata. The top 100 by citation count are listed; the percentile is the rank divided by the cohort size. 100 of the 100 entries have an abstract in OpenAlex. Counts were read on 29 October 2026 and will not be updated on this page, so a quoted rank stays verifiable. Full rules on the methodology page.

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