bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unbiased metagenomic sequencing for pediatric meningitis in Bangladesh reveals neuroinvasive Chikungunya virus outbreak and other unrealized pathogens
Authors: Saha Senjuti , Ramesh Akshaya , Kalantar Katrina , Malaker Roly , Hasanuzzaman Md , Khan Lillian M. , Mayday Madeline Y , Sajib M S I , Li Lucy M. , Langelier Charles , Rahman Hafizur , Crawford Emily D. , Tato Cristina M. , Islam Maksuda , Juan Yun-Fang , Bourcy Charles de , Dimitrov Boris , Wang James , Tang Jennifer , Sheu Jonathan , Egger Rebecca , De Carvalho Tiago Rodrigues , Wilson Michael R. , Saha Samir K , DeRisi Joseph L 
Published: March 2019

AbstractThe disease burden due to meningitis in low and middle-income countries remains significant and failure to determine an etiology impedes appropriate treatment for patients and evidence-based policy decisions for populations. Broad-range pathogen surveillance using metagenomic next-generation sequencing (mNGS) of RNA isolated from cerebral spinal fluid (CSF) provides an unbiased assessment for possible infectious etiologies. In this study, our objective was to use mNGS to identify etiologies of pediatric meningitis in Bangladesh.We conducted a retrospective case-control mNGS study on CSF from patients with known neurologic infections (n=36), idiopathic meningitis (n=25), without infection (n=30) and six environmental samples collected between 2012-2018. Using an open-access, cloud-based bioinformatics pipeline (IDseq) and machine learning, we identified potential pathogens which were confirmed through qPCR and Sanger sequencing. These cases were followed-up through phone/home-visits. The CSF samples were collected from children with WHO-defined meningeal signs during prospective meningitis surveillance at the largest pediatric referral hospital in Bangladesh.The 91 participants (42% female) ranged in age from 0-160 months (median: 9 months). In samples with known infectious causes of meningitis and without infections (n=66), there was 83% concordance between mNGS and conventional testing. In idiopathic cases (n=25), mNGS identified a potential etiology in 40% (n=10), including bacterial and viral pathogens. There were three instances of neuroinvasive Chikungunya virus (CHIKV). The CHIKV genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause systemic illness in 2017. CHIKV qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital (n=472) revealed 17 additional CHIKV meningitis cases. Orthogonal molecular confirmation of each mNGS-identified infection, case-based clinical data, and follow-up of patients substantiated the key findings.Using mNGS, we obtained a microbiological diagnosis for 40% of idiopathic meningitis cases and identified a previous unappreciated pediatric CHIKV meningitis outbreak. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis and facilitate informed policy decisions.
Sci-Hi-C: a single-cell Hi-C method for mapping 3D genome organization in large number of single cells
Authors: Ramani Vijay , Deng Xinxian , Qiu Ruolan , Lee Choli , Disteche Christine M , Noble William S , Duan Zhijun , Shendure Jay 
Published: March 2019

AbstractThe highly dynamic nature of chromosome conformation and three-dimensional (3D) genome organization leads to cell-to-cell variability in chromatin interactions within a cell population, even if the cells of the population appear to be functionally homogeneous. Hence, although Hi-C is a powerful tool for mapping 3D genome organization, this heterogeneity of chromosome higher order structure among individual cells limits the interpretive power of population based bulk Hi-C assays. Moreover, single-cell studies have the potential to enable the identification and characterization of rare cell populations or cell subtypes in a heterogeneous population. However, it may require surveying relatively large numbers of single cells to achieve statistically meaningful observations in single-cell studies. By applying combinatorial cellular indexing to chromosome conformation capture, we developed single-cell combinatorial indexed Hi-C (sci-Hi-C), a high throughput method that enables mapping chromatin interactomes in large number of single cells. We demonstrated the use of sci-Hi-C data to separate cells by karytoypic and cell-cycle state differences and to identify cellular variability in mammalian chromosomal conformation. Here, we provide a detailed description of method design and step-by-step working protocols for sci-Hi-C.
Simple Framework for Constructing Functional Spiking Recurrent Neural Networks
Authors: Kim Robert , Li Yinghao , Sejnowski Terrence J. 
Published: March 2019

AbstractCortical microcircuits exhibit complex recurrent architectures that possess dynamically rich properties. The neurons that make up these microcircuits communicate mainly via discrete spikes, and it is not clear how spikes give rise to dynamics that can be used to perform computationally challenging tasks. In contrast, continuous models of rate-coding neurons can be trained to perform complex tasks. Here, we present a simple framework to construct biologically realistic spiking recurrent neural networks (RNNs) capable of learning a wide range of tasks. Our framework involves training a continuous-variable rate RNN with important biophysical constraints and transferring the learned dynamics and constraints to a spiking RNN in a one-to-one manner. The proposed framework introduces only one additional parameter to establish the equivalence between rate and spiking RNN models. We also study other model parameters related to the rate and spiking networks to optimize the one-to-one mapping. By establishing a close relationship between rate and spiking models, we demonstrate that spiking RNNs could be constructed to achieve similar performance as their counterpart continuous rate networks.
Epistatic Networks Associated with Parent-of-Origin Effects on Metabolic Traits
Authors: Macias-Velasco Juan F , Pierre Celine L. St. , Wayhart Jessica P , Yin Li , Spears Larry , Miranda Mario A. , Funai Katsuhiko , Cheverud James M , Semenkovich Clay F , Lawson Heather A 
Published: March 2019

ABSTRACTParent-of-origin effects (POE) are unexpectedly common in complex traits, including metabolic and neurological diseases. POE can also be modified by the environment, but the architecture of these gene-by-environmental effects on phenotypes remains to be unraveled. Previously, quantitative trait loci (QTL) showing context-specific POE on metabolic traits were mapped in the F16 generation of an advanced intercross between LG/J and SM/J inbred mice. However, these QTL were not enriched for known imprinted genes, suggesting another mechanism is needed to explain these POE phenomena. Here, we use a simple yet powerful F1 reciprocal cross model to test the hypothesis that non-imprinted genes can generate complex POE on metabolic traits through genetic interactions with imprinted genes. Male and female mice from a F1 reciprocal cross of LG/J and SM/J strains were fed either high or low fat diets. We generated expression profiles from three metabolically-relevant tissues: hypothalamus, white adipose, and liver. We identified two classes of parent-of-origin expression biases: genes showing parent-of-origin-dependent allele-specific expression and biallelic genes that are differentially expressed by reciprocal cross. POE patterns of both gene classes are highly tissue-and context-specific, sometimes occurring only in one sex and/or diet cohort in a particular tissue. We then constructed tissue-specific interaction networks among genes from these two classes of POE. A key subset of gene pairs show significant epistasis in the F16 LG/J x SM/J advanced intercross data in cases where the biallelic gene fell within a previously-identified metabolic POE QTL interval. We highlight one such interaction in adipose, between Nnat and Mogat1, which associates with POE on multiple adiposity traits. Both genes localize to the endoplasmic reticulum of adipocytes and play a role in adipogenesis. Additionally, expression of both genes is significantly correlated in human visceral adipose tissue. The genes and networks we present here represent a set of actionable interacting candidates that can be probed to further identify the machinery driving POE on complex traits.
ESCRT-III/Vps4 controls heterochromatin-nuclear envelope attachments
Authors: Pieper Gerard H. , Sprenger Simon , Teis David , Oliferenko Snezhana 
Published: March 2019

AbstractIn eukaryotes chromosomes are compartmentalized within the nucleus delimited by the double membrane of the nuclear envelope (NE). Defects in the function and structure of the NE are linked to disease1,2. During interphase, the NE organizes the genome and regulates its expression3. As cells enter mitosis, chromosomes are released from the NE, which is then remodelled to form the daughter nuclei at mitotic exit4. Interactions between the NE and chromatin underpinning both interphase and post-mitotic NE functions are executed by inner nuclear membrane (INM) proteins such as members of the evolutionarily conserved chromatin-binding LEM-domain family5–8. How chromatin tethering by these transmembrane proteins is controlled in interphase and if such a regulation contributes to subsequent NE dynamics in mitosis remains unclear. Here we probe these fundamental questions using an emerging model organism, the fission yeastSchizosaccharomyces japonicus, which breaks and reforms the NE during mitosis9,10. We show that attachments between heterochromatin and the transmembrane Lem2-Nur1 complex are continuously remodelled in interphase by the ESCRT-III/AAA-ATPase Vps4 machinery. ESCRT-III/Vps4 mediates the release of Lem2-Nur1 from heterochromatin as a prerequisite for the timely progression through mitosis. Failure in this process leads to persistent association of chromosomes with the INM, which prevents Lem2-Nur1 from re-localizing to the sites of NE sealing around the mitotic spindle and severely delays re-establishment of nucleocytoplasmic compartmentalization. Our work establishes the INM transmembrane Lem2-Nur1 complex as a ‘substrate’ for ESCRT-III/Vps4 to couple dynamic tethering of chromosomes to the INM with the establishment of nuclear compartmentalization.
Multivariate Analysis Illuminates the Effects of Vacuum Drying on the Extractable and Nonextractable Polyphenols Profile of Loquat Fruit
Authors: Li Wenfeng , Wang Xv , Zhang Jing , Zhao Xin , Wu Yingmei , Tan Si , Zheng Qiaoran , Gao Xiaoxv 
Published: March 2019

AbstractThe current study evaluated the effects of vacuum drying on the whole polyphenol profile of loquat fruit, including extractive and nonextractive polyphenols. Absorbance analysis determined that total polyphenol content and antioxidant levels were higher in loquat fruit vacuum dried at 140 °C than in loquat fruit vacuum dried at 70 °C. The results of ultra‐HPLC–triple quadruple mass spectrum analysis showed that 15 phenolic acids and 17 flavonoids were found in dried loquat fruit. Multivariate integrative (MINT) sparse partial least square‐discriminant analysis showed that vacuum drying affects the polyphenol profile of loquat fruit. Co‐analysis of principal component analysis, partial least square‐discriminant analysis, and orthometric partial least square‐discriminant analysis revealed that vacuum drying mainly changed the content of chlorogenic acid, cryptochlorogenic acid, protocatechuic acid, phloretin, and hesperidin in loquat fruit. Chlorogenic acid (12.020 to 39.153 µg/g d.b. [dried base weight]), the main polyphenol in dried loquat fruit, was degraded to caffeic acid (0.028 to 2.365 µg/g d.b.) and protocatechuic acid (0.014 to 18.285 µg/g d.b.) during vacuum drying. Moreover, vacuum drying also induced the isomerization of chlorogenic acid into cryptochlorogenic acid (1.628 to 12.737 µg/g d.b.). These results might be used to develop dried loquat fruit with high levels of polyphenols and antioxidant activity.Practical ApplicationInterests in polyphenols of loquat fruit had increased greatly because of their possible role in health benefits. This work provided a holistic insight in the effects of vacuum drying on polyphenols profile of loquat fruit. Current results have contributed to the development of vacuum‐drying method, which produced loquat fruit rich in polyphenols. Furthermore, it also suggested that multivariate analysis was a feasible method to reveal the important changes of polyphenols profile during food processing.
Noise‐induced reduction in the attack rate of a planktivorous freshwater fish revealed by functional response analysis
Authors: Hanache Priscillia , Spataro Thierry , Firmat Cyril , Boyer Nicolas , Fonseca Paulo , Médoc Vincent 
Published: March 2019

AbstractAnthropogenic noise can affect animals physically, physiologically, and behaviourally. Although individual responses to noise are well documented, the consequences in terms of community structure, species coexistence, and ecosystem functioning remain fairly unknown.The impact of noise on predation has received a growing interest and alterations in trophic links are observed when animals shift from foraging to stress‐related behaviours, are distracted by noise, or because of acoustic masking. However, the experimental procedures classically used to quantify predation do not inform on the potential demographic impact on prey.We derived the relationship between resource use and availability (the functional response) for European minnows (Phoxinus phoxinus) feeding on dipteran larvae (Chaoborussp.) under two noise conditions: ambient noise and ambient noise supplemented with motorboat noise. The shape and magnitude of the functional response are powerful indicators of population outcomes and predator–prey dynamics. We also recorded fish behaviour to explore some proximate determinants of altered predation.For both noise conditions, fish displayed a saturating (typeII) functional response whose shape depends on two parameters: attack rate and handling time. Boat noise did not affect handling time but significantly reduced attack rate, resulting in a functional response curve of the same height but with a less steep initial slope. Fish exhibited a stress‐related response to noise including increased swimming distance, more social interactions, and altered spatial distribution.Our study shows the usefulness of the functional response approach to study the ecological impacts of noise and illustrates how the behavioural responses of predators to noise can modify the demographic pressure on prey. It also suggests that prey availability might mediate the negative effect of noise on predation. Community outcomes are expected if the reduced consumption of the main food sources goes with the overconsumption of alternative food sources, changing the distribution pattern of interaction strengths. Predation release could also trigger a trophic cascade, propagating the effect of noise to lower trophic levels.
Spatial and seasonal variability in the trophic role of aquatic insects: An assessment of functional feeding group applicability
Authors: Tierno de Figueroa José Manuel , López‐Rodríguez Manuel Jesús , Villar‐Argaiz Manuel 
Published: March 2019

AbstractFunctional feeding groups (FFGs) have been used over recent decades to classify aquatic insects according to their trophic resources and the mechanisms used to acquire them. Nonetheless, the classification of a taxon into anFFGis often based on its membership of a genus or family rather than on species level information. This extrapolation of theFFGmembership of one taxon to the remaining taxa within a group has led to misconceptions and erroneous conclusions.This study aimed to determine the amount of variation inFFGmembership within species among seasons and locations and whether this was related to resource availability. For this purpose, we sampled over two seasons (autumn and spring) at three altitudes in each of four basins, measuring the main trophic resources available for aquatic insects and collecting representatives of taxa traditionally assigned to each of the mainFFGs. Based on analyses of the diet of multiple individuals in each location and season, we calculated the percentage belonging to eachFFG.Diets differed widely among taxa, and within taxa they often varied significantly between sites in the same season and at the same site between different seasons. Species' diets could also differ between different river basins when specimens were collected at the same altitude and season. In some cases, although the primary food source remained the same, the contribution from a secondary source varied between sites. Although availability of the three main trophic resources (epilithic algae,fineand coarseparticulate organic matter) differed among sites, we found no association overall between the availability of these resources and insect diets.Our results agree with several recent studies that show that the diets of stream invertebrates vary widely in space and time, potentially indicative of widespread omnivory/opportunistic feeding. This makes classifying taxa into particularFFGs without collection of dietary data, or by assigning oneFFGto a taxon across all places and times, fraught with potential errors. These have possible repercussions for ecological studies related to matter cycles or food webs, amongst other issues. Some stream insects are consistently predaceous or have piercing mouthparts that constrain their diet. However, it appears increasingly likely that the majority of taxa, formerly labelled as scraper, shredder, and collector–gatherer or filterer, should be regarded as feeding on a range of sources and not routinely assigned into distinctFFGs (in the absence of local dietary data). We suggest researchers classify stream insect taxa as omnivores unless there are local data that show otherwise, or the taxa are obligate predators, feed by piercing or are otherwise physiologically constrained to a particular diet.
Oral health‐related quality of life and satisfaction of edentulous patients using conventional complete dentures and implant‐retained overdentures: An umbrella systematic review
Authors: Sharka Rayan , Abed Hassan , Hector Mark 
Published: March 2019

BackgroundLoss of teeth has a negative influence on essential oral functions. It is important to understand edentulous patients’ perceptions about the impacts of treatment options on their oral health‐related quality of life (OHRQoL) and satisfaction.AimsTo appraise the systematic reviews (with/without meta‐analysis) that investigate the impacts of complete conventional dentures (CCDs) and/or implant‐retained overdentures (IRODs) on the oral health‐related quality of life (OHRQoL) and satisfaction among edentulous patients.MethodsThe Joanna Briggs Institute (JBI) methodology for conduct of an umbrella systematic review was followed. Three database systems were used: Medline, Google Scholar and Cochrane Library. PROSPERO was searched for ongoing or recently completed systematic reviews. The reviews must report OHRQoL and patients’ satisfaction as outcomes.ResultsA total of eight reviews were included in data synthesis (six were systematic reviews without meta‐analysis, one was systematic review with meta‐analysis, and one was meta‐analysis). The level of evidence of all included reviews based on the Scottish Intercollegiate Guidelines Network ranged between 1+ and 1−.ConclusionThe results of this umbrella systematic review demonstrate the superiority of using IRODs compared with CCDs on the OHRQoL and patients’ satisfaction outcomes. However, this positive impact is more accentuated when patients demand implant treatment or cannot adapt to CCDs treatment. Financial factors and adaptive capability indeed affect patient tolerance to both treatment modalities.
Mortality of patients with haemophilia in Brazil: First report
Authors: Jardim Leticia Lemos , van der Bom Johanna G. , Caram‐Deelder Camila , Gouw Samantha Claudia , Leal Cherchiglia Mariangela , Rezende Suely Meireles 
Published: March 2019

IntroductionBrazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown.AimTo analyse mortality and its causes in Brazilian patients with haemophilia from 2000 to 2014.MethodsThe number of deceased patients with haemophilia and causes of death were obtained from the Brazilian National Mortality Information System (SIM), according to the 10th International Classification of Diseases (ICD‐10). Standardized mortality ratios (SMR) were calculated to estimate the rate of overall death of patients with haemophilia relative to that of the Brazilian general male population.ResultsA total of 784 deaths were identified in the period of 15 years. Mortality of patients with haemophilia was 13% higher when compared with the general male population (SMR 1.13, 95% CI: 1.01‐1.16). Haemorrhage was the main cause of death (n = 254; 32.4%) of which 137 (54%) was intracranial haemorrhage. The total number of deaths due to HIV decreased over the years, and an increase in deaths due to cancer and cardiovascular disease was observed. A total of 129 deaths (16.5%) were related to hepatitis infection, of whom, 109 (86.5%) patients also presented with cirrhosis and hepatocellular carcinoma or other liver diseases.ConclusionMortality rate of Brazilian patients with haemophilia decreased over the evaluated period. Intracranial haemorrhage is still an important cause of death in these patients, which requires major effort for prevention. Death due to age‐related cardiovascular disease and cancer has increased over the years, following the same tendency observed in developed countries.
The peripheral differentiation of human natural killer T cells
Authors: Liu Jie , Hill Brenna J , Darko Sam , Song Kaimei , Quigley Máire F , Asher Tedi E , Morita Yohei , Greenaway Hui Y , Venturi Vanessa , Douek Daniel C , Davenport Miles P , Price David A , Roederer Mario 
Published: March 2019

AbstractThe peripheral maturation of human CD1d‐restricted natural killer T (NKT) cells has not been well described. In this study, we identified four major subsets of NKT cells in adults, distinguished by the expression of CD4, CD8 and CCR5. Phenotypic analysis suggested a hierarchical pattern of differentiation, whereby immature CD4+CD8−CCR5− cells progressed to an intermediate CD4+CD8−CCR5+ stage, which remained less differentiated than the CD4−CD8− and CD4−CD8+ subsets, both of which expressed CCR5. This interpretation was supported by functional data, including clonogenic potential and cytokine secretion profiles, as well as T‐cell receptor (TCR) excision circle analysis. Moreover, conventional and high‐throughput sequencing of the corresponding TCR repertoires demonstrated significant clonotypic overlap within individuals, especially between the more differentiated CD4−CD8− and CD4−CD8+ subsets. Collectively, these results mapped a linear differentiation pathway across the post‐thymic landscape of human CD1d‐restricted NKT cells.