bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global trends in air travel: implications for connectivity and resilience to infectious disease threats
Authors: Tuite Ashleigh R. , Bhatia Deepit , Moineddin Rahim , Bogoch Isaac I. , Watts Alexander G. , Khan Kamran 
Published: April 2020

ABSTRACTBackgroundIncreased connectivity via air travel can facilitate the geographic spread of infectious diseases. The number of travelers alone does not explain risk; passenger origin and destination will also influence risk of disease introduction and spread. We described trends in international air passenger numbers and connectivity between countries with different capacities to detect and respond to infectious disease threats.MethodsWe used the Fragile States Index (FSI) as an annual measure of country-level resilience and capacity to respond to infectious disease events. Countries are categorized as: Sustainable, Stable, Warning, or Alert, in order of increasing fragility. We included data for 177 sovereign states for the years 2007 to 2016. Annual inbound and outbound international air passengers for each country were obtained for the same time period. We examined trends in FSI score, trends in worldwide air travel, and the association between a state’s FSI score and air travel.ResultsAmong countries included in the FSI rankings, the total number of passengers increased from 0.791 billion to 1.28 billion between 2007 and 2016. Increasing fragility was associated with a decrease in travel volumes, with a 2.9% (95% CI: 2.3-3.5%) reduction in passengers per 1-unit increase in FSI score. Overall, travel between countries of different FSI categories either increased or remained stable. The greatest increase was observed for travel to Warning countries from Warning countries, with an annual increase of 8,967,623 passengers (95%CI: 6,546,494 to 11,388,753) over the study period.ConclusionsThe world’s connectivity via air travel has increased dramatically over the past decade. There has been notable growth in travel from Warning and Stable countries, which comprise more than three-quarters of international air travel passengers. These countries may have suboptimal capacity to detect and respond to infectious disease threats that emerge within their borders.
Revealing the functions of supra-temporal and insular auditory responsive areas in humans
Authors: Wang Qian , Luo Lu , Xu Na , Wang Jing , Gao Yayue , Li Siqi , Wang Mengyang , Teng Pengfei , Guan Yuguang , Zhou Jian , Li Tianfu , Tian Xing , Luan Guoming 
Published: April 2020

ABSTRACTThe human auditory sensory area, which includes primary and non-primary auditory cortices, has been considered to locate in the supra-temporal lobe for more than a century. Recently, accumulating evidence shows that the posterior part of insula responses to sounds under non-task states with relevant short latencies. However, whether posterior insula (InsP) contribute to forming auditory sensation remains unclear. Here we addressed this issue by recording and stimulation directly on the supra-temporal and insular areas via intracranial electrodes from 53 epileptic patients. During passive listening to a non-speech sound, the high-γ (60-140 Hz) active rate of InsP (68.8%) was approximate to the non-primary auditory areas (72.4% and 79.0%). Moreover, we could not distinguish InsP from supra-temporal subareas by either activation, latency, temporal pattern or lateral dominance of sound induce high-γ. On the contrary, direct electrical stimulation evoked auditory sensations effectively on supra-temporal subareas (> 65%), while sparsely on InsP (9.49%). The results of cortico-cortical evoked potentials (CCEPs) showed strong bidirectional connectivity within supra-temporal areas, but weak connectivity between supra-temporal areas and InsP. These findings suggest that even the InsP has similar basic auditory response properties to the primary or non-primary cortex, it may not directly participate in the formation of auditory perception.
Facilitative priority effects drive parasite assembly under coinfection
Authors: Halliday Fletcher W. , Penczykowski Rachel M. , Barrès Benoit , Eck Jenalle L. , Numminen Elina , Laine Anna-Liisa 
Published: April 2020

AbstractHost individuals are often coinfected with diverse parasite assemblages, resulting in complex interactions among parasites within hosts. Within hosts, priority effects occur when the infection sequence alters the outcome of interactions among parasites. Yet, the role of host immunity in this process remains poorly understood. We hypothesized that the host response to first infection could generate priority effects among parasites, altering the assembly of later arriving strains during epidemics. We tested this by infecting sentinel host genotypes ofPlantago lanceolatawith strains of the fungal parasite,Podosphaera plantaginis, and measuring susceptibility to subsequent infection during experimental and natural epidemics. In these experiments, prior infection by one strain often increased susceptibility to other strains, and these facilitative priority effects altered the structure of parasite assemblages, but this effect depended on host genotype, host population, and parasite genotype. Thus, host genotype, spatial structure, and priority effects among strains all independently altered parasite assembly. Then, using a fine-scale survey and sampling of infections on wild hosts in several populations, we identified a signal of facilitative priority effects, which altered parasite assembly during natural epidemics. Together, these results provide evidence that within host priority effects by early arriving strains can drive parasite assembly, with implications for how strain diversity is spatially and temporally distributed during epidemics.
Predicting candidate genes from phenotypes, functions, and anatomical site of expression
Authors: Chen Jun , Althagafi Azza , Hoehndorf Robert 
Published: April 2020

ABSTRACTMotivationOver the past years, many computational methods have been developed to incorporate information about phenotypes for disease gene prioritization task. These methods generally compute the similarity between a patient’s phenotypes and a database of gene-phenotype to find the most phenotypically similar match. The main limitation in these methods is their reliance on knowledge about phenotypes associated with particular genes, which is not complete in humans as well as in many model organisms such as the mouse and fish. Information about functions of gene products and anatomical site of gene expression is available for more genes and can also be related to phenotypes through ontologies and machine learning models.ResultsWe developed a novel graph-based machine learning method for biomedical ontologies which is able to exploit axioms in ontologies and other graph-structured data. Using our machine learning method, we embed genes based on their associated phenotypes, functions of the gene products, and anatomical location of gene expression. We then develop a machine learning model to predict gene–disease associations based on the associations between genes and multiple biomedical ontologies, and this model significantly improves over state of the art methods. Furthermore, we extend phenotype-based gene prioritization methods significantly to all genes which are associated with phenotypes, functions, or site of expression.AvailabilitySoftware and data are available athttps://github.com/bio-ontology-research-group/DL2Vec.Contactrobert.hoehndorf@kaust.edu.sa
PremalignantNf1, Trp53-null Oligodendrocyte Precursor Cells Become Stalled in a Heterogeneous State of Replication Stress Before Gliomagenesis
Authors: Sutcliffe Matthew D. , Galvao Rui P. , Wang Lixin , Kim Jungeun , Rosenfeld Lauren K. , Singh Shambhavi , Zong Hui , Janes Kevin A. 
Published: April 2020

AbstractCancer evolves from premalignant clones that accumulate mutations and adopt unusual cell states to achieve transformation. Previously, we pinpointed the oligodendrocyte precursor cell (OPC) as a cell-of-origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducibleNf1–Trp53loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection and determined gene-expression changes by bulk RNA sequencing and a fluctuation analysis, called stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days afterNf1–Trp53deletion, while bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, stochastic profiling revealed a spectrum of stem-progenitor (Axl, Aldh1a1), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected very few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, we identified mutant OPCs that strongly expressed key effectors of nonsense-mediated decay (Upf3b) and homology-dependent DNA repair (Rad51c, Slx1b, Ercc4) along with DNA-damage markers suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease (Mus81) andRin1,a Ras–Raf antagonist and possible counterbalance toNf1loss. At 150 days,Rin1was microdeleted in some gliomas and downregulated in all others. Replication stress may pose a considerable bottleneck that must be resolved for gliomas to initiate.Statement of significanceIn situ stochastic profiling of heterogeneous cell states in a mouse model of glioma uncovers regulatory confusion in a glioma cell-of-origin and defines a state of replication stress that precedes tumor initiation.
Using spatial genetics to quantify mosquito dispersal for control programs
Authors: Filipović I , Hapuarachchi HC , Tien WP , Muhammed ABAR , Lee C , Tan CH , Devine GJ , Rašić G 
Published: April 2020

AbstractBackgroundHundreds of millions of people get a mosquito-borne disease every year, of which nearly one million die. Mosquito-borne diseases are primarily controlled and mitigated through the control of mosquito vectors. Accurately quantified mosquito dispersal in a given landscape is critical for the design and optimization of the control programs, yet the field experiments that measure dispersal of mosquitoes recaptured at certain distances from the release point (mark-release-recapture MRR studies) are challenging for such small insects and often unrepresentative of the insect’s true field behavior. Using Singapore as a study site, we show how mosquito dispersal patterns can be characterized from the spatial analyses of genetic relatedness among individuals sampled over a short time span without interruption of their natural behaviors.Methods and FindingsWe captured ovipositing females ofAedes aegypti, a major arboviral disease vector, across floors of high-rise apartment blocks and genotyped them using thousands of genome-wide SNP markers. We developed a methodology that produces a dispersal kernel for distance that results from one generation of successful breeding (effective dispersal), using the distances separating full siblings, 2ndand 3rddegree relatives (close kin). In Singapore, the estimated dispersal distance kernel was exponential (Laplacian), giving the mean effective dispersal distance (and dispersal kernel spread σ) of 45.2 m (95%CI: 39.7-51.3 m), and 10% probability of dispersal >100 m (95%CI: 92-117 m). Our genetic-based estimates matched the parametrized dispersal kernels from the previously reported MRR experiments. If few close-kin are captured, a conventional genetic isolation-by-distance analysis can be used, and we show that it can produce σ estimates congruent with the close-kin method, conditioned on the accurate estimation of effective population density. We also show that genetic patch size, estimated with the spatial autocorrelation analysis, reflects the spatial extent of the dispersal kernel ‘tail’ that influences e.g. predictions of critical radii of release zones andWolbachiawave speed in mosquito replacement programs.ConclusionsWe demonstrate that spatial genetics (the newly developed close-kin analysis, and conventional IBD and spatial autocorrelation analyses) can provide a detailed and robust characterization of mosquito dispersal that can guide operational vector control decisions. With the decreasing cost of next generation sequencing, acquisition of spatial genetic data will become increasingly accessible, and given the complexities and criticisms of conventional MRR methods, but the central role of dispersal measures in vector control programs, we recommend genetic-based dispersal characterization as the more desirable means of parameterization.
Assessment of prevalence and risk factors for intestinal parasitosis, malnutrition and anemia among school children in Ghindae area, Eritrea
Authors: Kesete Yafet , Tesfahiwet Huruy , Fessehaye Ghimja , Kidane Yohana , Tekle Yafet , Yacob Asmerom , Seltene Biemnet 
Published: April 2020

AbstractBackgroundIntestinal parasitic infections, anemia, and malnutrition are very endemic in resource-limited regions. School-aged children are at greater risk for the disease than any other age group as they are more susceptible to parasitosis, associated undergrowth and anemia. This study is aimed at evaluating the risk factors of intestinal parasitosis, malnutrition and anemia amongst elementary and junior school students in Ghindae area, Eritrea.MethodsA cross sectional study was conducted in 6 schools around Ghindae from February to April 2018. 450 children were randomly selected for analysis and consent was taken from guardians. The pertinent sociodemographic data was collected and anthropometric measurements were carried out to determine the proportion of students with malnutrition, stunting and thinness. Fecal samples were examined by formal concentration technique and blood specimen was collected for the assessment of hemoglobin using hemocue analyzer.ResultsThe overall prevalence of intestinal parasitosis was 45.3%. Protozoa infections (38.2%) were more prevalent than soil-transmitted helminthes infections (10.4%). The presence of different intestinal parasitic infections has statistically significant association with the residence area, washing habits, source of water, types of schools and type of latrine used with (p < 0.05). The prevalence of malnutrition was 37.1% with 18.5% stunting and 21.2% thinness. Malnutrition was in higher prevalence in semi-urban areas outside Ghindae. Students from Embatkala and Dongolo had 4.77 and 2.86 times higher odds of having low BMI for age than their counterpart respectively. The current prevalence of anemia was 12.4%, out of which, 7.6 % had mild while 4.4% of them had moderate anemia and 0.4% were severely anemic.ConclusionThe prevalence of intestinal parasitic infections, especially, protozoan infection was very high in the school children. Stunting was increased rate in rural areas around Ghindae. The prevalence of anemia was regarded as mild health burden. The high prevalence of parasitic infections in these children indicates that the protozoa and helminthes concerned are very common in the environment of these area and results of the risk factors analysis suggest that the transmission is from several routes. Access to clean water and latrines, with some hygiene and sanitation communication activities, in addition to introduction of micronutrient programs could improve health of children in that area.
Early behavior of Madrid Covid-19 disease outbreak: A mathematical model
Authors: García-Iglesias Daniel , de Cos Juez Francisco Javier 
Published: April 2020

AbstractIntroductionMadrid Covid-19 disease outbreak started on 28 February 2020 and since then it became the main Covid-19 disease cluster in Spain. On 26 March 2020, a total of 17166 cases were already reported, with 2090 deaths. Globally a R0 index of 2-3 has been reported. We aimed to build an experimental mathematical model that help to analyze the early characteristics of Madrid Covid-19 disese outbreak and to explore the actual R0 index on Madrid Covid-19 outbreak.Material and MethodsA simulated mathematical model was built, based on a SIR epidemiological model and the reported characteristics of Wuhan Covid-19 disease outbreak. Monte Carlo simulations were further done to estimate the R0 value over time in the Madrid Covid-19 disease outbreak.ResultsMean estimated R0 value along the early period is of 2.22 (+/-1.21 SD). A significant increase of 0.093 (+/-0.037, p=0.025) in R0 value each day of outbreak is found.ConclussionsOur proposed Mathematical Simulation model may be useful to evaluate early characteristics of this outbreak. The present work is the first reported estimation of R0 value in the Spanish Madrid Covid-19 outbreak, with similar results to the previous reported in the Wuhan outbreak, although it may suggest a slightly increase on R0 along time.
Autonomous Magnetic Resonance Imaging
Authors: Ravi Keerthi Sravan , Geethanath Sairam 
Published: April 2020

AbstractAccess to Magnetic Resonance Imaging (MRI) across developing countries from being prohibitive to scarcely available. For example, eleven countries in Africa have no scanners. One critical limitation is the absence of skilled manpower required for MRI usage. Some of these challenges can be mitigated using autonomous MRI (AMRI) operation. In this work, we demonstrate AMRI to simplify MRI workflow by separating the required intelligence and user interaction from the acquisition hardware. AMRI consists of three components: user node, cloud and scanner. The user node voice interacts with the user and presents the image reconstructions at the end of the AMRI exam. The cloud generates pulse sequences and performs image reconstructions while the scanner acquires the raw data. An AMRI exam is a custom brain screen protocol comprising of one T1-, T2- and T2*-weighted exams. A neural network is trained to incorporate Intelligent Slice Planning (ISP) at the start of the AMRI exam. A Look Up Table was designed to perform intelligent protocolling by optimising for contrast value while satisfying signal to noise ratio and acquisition time constraints. Data were acquired from four healthy volunteers for three experiments with different acquisition time constraints to demonstrate standard and self-administered AMRI. The source code is available online. AMRI achieved an average SNR of 22.86 ± 0.89 dB across all experiments with similar contrast. Experiment #3 (33.66% shorter table time than experiment #1) yielded a SNR of 21.84 ± 6.36 dB compared to 23.48 ± 7.95 dB for experiment #1. AMRI can potentially enable multiple scenarios to facilitate rapid prototyping and research and streamline radiological workflow. We believe we have demonstrated the first Autonomous MRI of the brain.
Double trouble? When a pandemic and seasonal virus collide
Authors: Zipfel Casey , Colizza Vittoria , Bansal Shweta 
Published: April 2020

AbstractAs healthcare capacities in the US and Europe reach their limits due to a surge in the COVID-19 pandemic, both regions enter the 2020-2021 influenza season. Southern hemisphere countries that had suppressed influenza seasons provide a hopeful example, but the lack of reduction in influenza in the 2019-2020 influenza season and heterogeneity in nonpharmaceutical and pharmaceutical interventions show that we cannot assume the same effect will occur globally. The US and Europe must promote the implementation and continuation of these measures in order to prevent additional burden to healthcare systems due to influenza.
RNF213variation, a broader role in neurovascular disease in Caucasian and Japanese populations
Authors: Lorenzo-Betancor Oswaldo , Blackburn Patrick R. , Farrugia Luca , Soto-Beasley Alexandra I. , Walton Ronald L. , Edwards Emily , Tawk Rabih G. , Klee Eric W. , Freeman William D. , Miller David , Meschia James , Ross Owen A. 
Published: April 2020

AbstractMoyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease that predominantly affects East Asian populations. The major genetic mutation associated with MMD in Asian populations is the p.R4810K substitution in Ring Finger Protein 213 (RNF213). Interestingly, variants in theRNF213gene have also been implicated in intracranial aneurysms (IA) in French-Canadian population, suggesting that variation in this gene may play a broader role in cerebrovascular phenotypes. In a recent genome-wide association study (GWAS) in a Caucasian population, variants rs6565653 and rs12601526 in theSolute Carrier Family 26 Member 11(SLC26A11) gene, which is less than 10kb away fromRNF213, showed a suggestive association with young onset ischemic stroke. We propose that the signal could be tagging an association with common variation in theRNF213gene. We analyzed the linkage disequilibrium (LD) pattern in theSLC26A11-RNF213gene region and we observed a high LD between variants in this region based on D’ values. We show thatSLC26A11rs6565653 variant tagsRNF213rs12944088, a missense variant that is more common among subjects with IA than in healthy individuals. Given the fact that rs6565653 tags severalRNF213variants, it is highly likely that some of these tagged variants modify the risk of suffering stroke. The LD analyses suggest that theSLC26A11signal from the young onset ischemic stroke GWAS performed in a Caucasian population is also tagging variation at theRNF213loci, supporting the hypothesis thatRNF213variation may result in a variety of neurovascular disorders including an increased risk and/or worse prognosis following ischemic stroke in Caucasian population.
The Crohn’s disease-related AIEC strain LF82 assembles a biofilm-like matrix to protect intracellular microcolonies from phagolysosomal attack
Authors: Prudent Victoria , Demarre Gaëlle , Vazeille Emilie , Wery Maxime , Ravet Antinéa , Quenech’Du Nicole , Girault Julie Dauverd , Bringer Marie-Agnès , Descrimes Marc , Barnich Nicolas , Rimsky Sylvie , Morillon Antonin , Espéli Olivier 
Published: April 2020

AbstractPatients with Crohn’s disease exhibit abnormal colonization of the intestine by proteobacteria, and among these bacteria, the adherent invasiveE. coli(AIEC) family. They are predominant in the mucus, adhere to epithelial cells, colonize them and survive inside macrophages. We recently demonstrated that the acclimation of the AIEC strain LF82 to phagolysosomal stress requires stringent and SOS responses. Such adaptation involves a long lag phase in which many LF82 cells become antibiotic tolerant. Later during infection, they proliferate in vacuoles and form colonies harboring dozens of LF82 bacteria. In the present work, we investigated the mechanism sustaining this phase of growth. We found that intracellular LF82 produced an extrabacterial matrix composed of exopolysaccharides and amyloid fibers that surrounded each individual LF82 cell. This matrix acts as a biofilm and controls the formation of LF82 intracellular bacterial communities (IBCs) inside phagolysosomes for several days post infection. Using genomics assays, we characterized the gene set involved in IBCs formation and revealed the crucial role played by a pathogenicity island presents in the genome of most AIEC strains in this process. Iron capture, by the yersiniabactin system encoded by this pathogenicity island, is essential to form IBC and LF82 survival within macrophages. These results demonstrate that AIEC have developed a sophisticated strategy to establish their replicative niche within macrophages, which might have implications for envisioning future antibacterial strategies for Crohn’s disease.
Culture conditions antagonize lineage-promoting signaling in the mouse blastocyst
Authors: Frum Tristan , Ralston Amy 
Published: April 2020

AbstractThe mouse preimplantation embryo is a paradigm for discovery of the molecular principles governing formation of specific cell types during development. We show that conditions commonly used forex vivoculture of preimplantation development are themselves antagonistic to a pathway that is critical for blastocyst lineage commitment.