bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants: a prospective cohort study
Authors: Parker Edward P. K. , Bronowski Christina , Sindhu Kulandaipalayam Natarajan C. , Babji Sudhir , Benny Blossom , Carmona-Vicente Noelia , Chasweka Nedson , Chinyama End , Cunliffe Nigel A. , Dube Queen , Giri Sidhartha , Grassly Nicholas C. , Gunasekaran Annai , Howarth Deborah , Immanuel Sushil , Jere Khuzwayo C. , Kampmann Beate , Lowe Jenna , Mandolo Jonathan , Praharaj Ira , Rani Bakthavatsalam Sandya , Silas Sophia , Srinivasan Vivek Kumar , Turner Mark , Venugopal Srinivasan , Verghese Valsan Philip , Darby Alistair C. , Kang Gagandeep , Iturriza-Gómara Miren 
Published: November 2020

AbstractIdentifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. We measured maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. ORV shedding and seroconversion rates were significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk were negatively correlated with ORV response in India and Malawi, and this was mediated partly by a reduction in ORV replication. In the UK, ORV replication was not inhibited despite comparable maternal antibody levels. In both India and Malawi, pre-vaccination microbiota diversity was negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.
HIV TREATMENT OUTCOMES IN RURAL GEORGIA USING TELEMEDICINE
Authors: Lawal Folake J. , Omotayo Moshood O. , Lee Tae Jin , Rao Arni S.R. Srinivasan , Vazquez Jose A. 
Published: November 2020

AbstractBackgroundThe dearth of specialized healthcare services contributes to the ongoing HIV epidemic. Telemedicine (TM) is a potential tool to improve HIV care, but little is known about its effectiveness when compared to traditional (face-to-face) (F2F) care in rural populations. The objective of this study is to examine the effectiveness of HIV care delivered through TM compared to F2F care.MethodsWe conducted a retrospective chart review of a subset of HIV patients who attended TM clinic in Dublin Georgia, and conventional F2F clinic in Augusta, Georgia between May 2017 to April 2018. All TM patients were matched to F2F patients based on gender, age, and race. HIV Viral Load (VL) and gain in CD4 counts were compared using T-test and Snedecor Statistics.Results385 patients were included in the analyses (F2F=200, TM=185). Mean CD4 in the TM group was higher (643.9 cells/mm3) than the F2F group (596.3 cells/mm3) (p< 0.001). There was no statistically significant difference in VL reduction and control. Thirty-eight of eighty-five patients with detectable VL achieved viral suppression during the study period (F2F = 24/54, TM =14/31), with a mean change of −3.34 × 104and −1.24 × 104respectively, p = 1.00. Mean VL was F2F = 416.8 cp/ml, TM = 713.4 cp/ml, p = 0.3.ConclusionTM was associated with outcome measures comparable to F2F. Increased access to specialty HIV care through TM can facilitate HIV control in communities with limited healthcare access in rural US. Rigorous prospective evaluation of TM for HIV care effectiveness is warranted.Article SummaryTelemedicine can be useful in improving access to specialist outpatient care for HIV and other chronic diseases, in remote communities with limited resources. Telemedicine can lead to similar outcomes when compared to traditional face-to-face outpatient consultations. This is especially true currently with COVID-19.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
Authors: Lau Billy T. , Pavlichin Dmitri , Hooker Anna C. , Almeda Alison , Shin Giwon , Chen Jiamin , Sahoo Malaya K. , Huang ChunHong , Pinsky Benjamin A. , Lee HoJoon , Ji Hanlee P. 
Published: November 2020

ABSTRACTBackgroundThe genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contract tracing.MethodsLeveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints.ResultsWe built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and rare ones that occur in only small fraction of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome.ConclusionsWe conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients, mutations demarcating dominant species and the prevalence of mutation signatures, of which a significant number were relatively unique. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.
Preferential observation of large infectious disease outbreaks leads to consistent overestimation of intervention efficacy
Authors: Zelner Jon , Masters Nina , Broen Kelly , Lofgren Eric 
Published: November 2020

AbstractData from infectious disease outbreaks in congregate settings are often used to elicit clues about which types of interventions may be useful in other facilities. This is commonly done using before-and-after comparisons in which the infectiousness of pre-intervention cases is compared to that of post-intervention cases and the difference is attributed to intervention impact. In this manuscript, we show how a tendency to preferentially observe large outbreaks can lead to consistent overconfidence in how effective these interventions actually are. We show, in particular, that these inferences are highly susceptible to bias when the pathogen under consideration exhibits moderate-to-high amounts of heterogeneity in infectiousness. This includes important pathogens such as SARS-CoV-2, influenza, Noroviruses, HIV, Tuberculosis, and many others
Mantis: flexible and consensus-driven genome annotation
Authors: Queirós Pedro , Delogu Francesco , Hickl Oskar , May Patrick , Wilmes Paul 
Published: November 2020

AbstractBackgroundThe past decades have seen a rapid development of the (meta-)omics fields, producing an unprecedented amount of data. Through the use of well-characterized datasets we can infer the role of previously functionally unannotated proteins from single organisms and consortia. In this context, protein function annotation allows the identification of regions of interest (i.e. domains) in protein sequences and the assignment of biological functions. Despite the existence of numerous tools, some challenges remain, specifically in terms of speed, flexibility, and reproducibility. In the era of big data it also becomes increasingly important to cease limiting our findings to a single reference, coalescing knowledge from different data sources, thus overcoming some limitations in overly relying on computationally generated data.ResultsWe implemented a protein annotation tool - Mantis, which uses text mining to integrate knowledge from multiple reference data sources into a single consensus-driven output. Mantis is flexible, allowing for total customization of the reference data used, adaptable, and reproducible across different research goals and user environments. We implemented a depth-first search algorithm for domain-specific annotation, which led to an average 0.038 increase in precision when compared to sequence-wide annotation. Mantis is fast, annotating an average genome in 25-40 minutes, whilst also outputting high-quality annotations (average coverage 81.4%, average precision 0.892).ConclusionsMantis is a protein function annotation tool that produces high-quality consensusdriven protein annotations. It is easy to set up, customize, and use, scaling from single genomes to large metagenomes. Mantis is available under the MIT license available athttps://github.com/PedroMTQ/mantis.
Navigating through chemical space and evolutionary time across the Australian continent in plant genusEremophila
Authors: Gericke Oliver , Fowler Rachael M. , Heskes Allison M. , Bayly Michael J. , Semple Susan J. , Ndi Chi P. , Stærk Dan , Løland Claus J. , Murphy Daniel J. , Buirchell Bevan J. , Møller Birger L. 
Published: November 2020

AbstractEremophilais the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize manyEremophilaspecies as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships betweenEremophilaand related genera in the tribe. Unique and structurally diverse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite diversity in a chemo-evolutionary framework applying a combination of molecular phylogenetic and state-of-the-art computational metabolomics tools to build a dataset involving leaf samples from a total of 291 specimens ofEremophilaand allied genera. The chemo-evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution) and medicinal properties (traditional medicinal uses and antibacterial studies) augmenting our understanding of complex interactions in biological systems.
Runcer-Necromancer: A Method To Rescue Data From An Interrupted Run On MGISEQ-2000
Authors: Pavlova Anna , Belova Vera , Afasizhev Robert , Bulusheva Irina , Rebrikov Denis , Korostin Dmitriy 
Published: November 2020

AbstractDuring the sequencing process, problems can occur with any device including the MGISEQ-2000 (DNBSEQ-G400) platform. We encountered a power outage that resulted in a temporary shutdown of a sequencer in the middle of the run. Since barcode reading in MGISEQ-2000 takes place at the end of the run, it was impossible to use non-demultiplexed raw data. We decided to completely use up the same cartridge with reagents and flow cell loaded with DNB and started a new run in a shortened custom mode. We figured out how the MGISEQ-2000 converts preliminary data in .cal format into .fastq files and wrote a script named “Runcer-Necromacer” for merging .fastq files based on the analysis of their headers (available online:https://github.com/genomecenter/runcer-necromancer). Read merging proved to be possible because the MGISEQ-2000 flow cell has a patterned structure and each DNB has invariable coordinates on it, regardless of its position on the flow cell stage. We demonstrated the correctness of data merging by comparing sample analysis results with previously obtained .fastq files for them. Thus, we confirmed that it is possible to restart the device and save both parts of the interrupted run.
Testing alternative phylogenetic hypotheses for the tent tortoise species complex (Reptilia, Testudinidae) using multiple data types and methods
Authors: Zhao Zhongning , Heideman Neil , Oosthuizen Jaco , Hofmeyr Margaretha D. 
Published: November 2020

AbstractWe examined genetic differentiation in the highly polymorphic and taxonomically confusing tent tortoise (Psammobates tentorius) species complex in southern Africa, using three types of molecular markers (nDNA, mtDNA and microsatellite DNA) and morphological data. The Approximate Bayesian Computation based simulation analyses advocated an alternative phylogenetic hypothesis for the tent tortoise species complex, which was better and more inclusive in explaining its genealogical history. Based on the evidence derived from the sequence, microsatellite and morphology data, a four species scheme (among the seven mtDNA clades) appears to be the best taxonomic solution for the systematic puzzle of theP. tentoriusspecies complex, namely, “C1+C4+C5+C7”, “C3”, “C2” and “C6”. The microsatellite datasets yielded similar genetic structure and gene flow patterns among the seven mtDNA clades in comparison to the sequence DNA. Evidence was found of possible hybridization between C1 and C2 in their intergradation zone, but not between C2 and C4. Results of the inbreeding analyses provided strong evidence of inbreeding in the eastern population of C1 and southern population of C2, which may be indicative of a bottleneck effect.
Learning to live with Dale’s principle: ANNs with separate excitatory and inhibitory units
Authors: Cornford Jonathan , Kalajdzievski Damjan , Leite Marco , Lamarquette Amélie , Kullmann Dimitri M. , Richards Blake 
Published: November 2020

AbstractThe units in artificial neural networks (ANNs) can be thought of as abstractions of biological neurons, and ANNs are increasingly used in neuroscience research. However, there are many important differences between ANN units and real neurons. One of the most notable is the absence of Dale’s principle, which ensures that biological neurons are either exclusively excitatory or inhibitory. Dale’s principle is typically left out of ANNs because its inclusion impairs learning. This is problematic, because one of the great advantages of ANNs for neuroscience research is their ability to learn complicated, realistic tasks. Here, by taking inspiration from feedforward inhibitory interneurons in the brain we show that we can develop ANNs with separate populations of excitatory and inhibitory units that learn just as well as standard ANNs. We call these networks Dale’s ANNs (DANNs). We present two insights that enable DANNs to learn well: (1) DANNs are related to normalization schemes, and can be initialized such that the inhibition centres and standardizes the excitatory activity, (2) updates to inhibitory neuron parameters should be scaled using corrections based on the Fisher Information matrix. These results demonstrate how ANNs that respect Dale’s principle can be built without sacrificing learning performance, which is important for future work using ANNs as models of the brain. The results may also have interesting implications for how inhibitory plasticity in the real brain operates.
Grapevine microbiota reflect diversity among compartments and complex interactions within and among root and shoot systems
Authors: Swift Joel F. , Hall Megan E. , Harris Zachary N. , Kwasniewski Misha T. , Miller Allison J. 
Published: November 2020

AbstractBackgroundWithin an individual plant, different compartments (e.g. roots, leaves, fruits) host distinct communities of microorganisms due to variation in structural characteristics and resource availability. Grafting, which joins the root system of one individual with the shoot system of a second genetically distinct individual, has the potential to bring the microbial communities of different genotypes together. An important question is the extent to which unique root system and shoot system genotypes, when grafted together, influence the microbiota of the graft partner. Our study sought to answer this question by utilizing an experimental vineyard composed of ‘Chambourcin’ vines growing ungrafted and grafted to three different rootstocks, replicated across three irrigation treatments. We characterized bacterial and fungal communities in roots, leaves, and berries, as well as surrounding soil. Our objectives were to (1) characterize the microbiota of compartments within the root system (roots and adjacent soil) and the shoot system (leaves and berries), (2) determine the influence of rootstock genotypes, irrigation, and their interaction on the microbiota of aboveground and belowground compartments, and (3) investigate the distribution of microorganisms implicated in the late-season grapevine bunch rot disease sour rot (Acetobacterales and Saccharomycetes).ResultsCompartments were significantly differentiated in bacterial and fungal richness and composition. Abundance-based machine learning accurately predicted the compartment and differential abundance analysis showed a large portion of taxa differed significantly across compartments. Rootstock genotypes did not differ significantly in microbial community richness or composition; however, individual microbial taxa exhibited significant differences in abundance based on rootstock and irrigation treatment. The relative abundance of Acetobacterales and Saccharomycetes in the berry was influenced by complex interactions among rootstock genotype and irrigation.ConclusionOur results indicate that grapevine compartments retain distinct core microbiota regardless of the rootstock to which they are grafted. While rootstock genotype generally had a subtle impact on global patterns of microbial diversity, we found associations between rootstock genotypes and specific groups of microorganisms. Further experimental validation is needed in order to understand how associations with these microorganisms impacts a vine’s susceptibility to sour rot upon damage and whether the characteristics of wine are impacted.
COVID-19 genetic risk and Neanderthals: A case study highlighting the importance of scrutinizing diversity
Authors: Wohlers Inken , Calonga-Solís Verónica , Jobst Jan-Niklas , Busch Hauke 
Published: November 2020

AbstractRecent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. The first published study reported a 1bp insertion rs11385942 on chromosome 3 (1) and subsequent studies single nucleotide variants (SNVs) such as rs35044562, rs67959919 (2) and rs13078854 (3), all highly correlated with each other. Zeberg and Pääbo (4) subsequently traced them back to Neanderthal origin. They found that a 49.4 kb genomic region including the risk allele of rs35044562 is inherited from Neanderthals of Vindija in Croatia. Here we add a differently focused evaluation of this major genetic risk factor to these recent analyses. We show that (i) COVID-19-related genetic factors of three previously assessed Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic.
Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4
Authors: Hoeksema Marten A. , Shen Zeyang , Holtman Inge R. , Zheng An , Spann Nathan , Cobo Isidoro , Gymrek Melissa , Glass Christopher K. 
Published: November 2020

AbstractMechanisms by which non-coding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. Here, we evaluated effects of >50 million SNPs and InDels provided by five inbred strains of mice on the responses of macrophages to interleukin 4 (IL-4), a cytokine that plays pleiotropic roles in immunity and tissue homeostasis. Remarkably, of >600 genes induced >2-fold by IL-4 across the five strains, only 26 genes reached this threshold in all strains. By applying deep learning and motif mutation analyses to epigenetic data for macrophages from each strain, we identified the dominant combinations of lineage determining and signal-dependent transcription factors driving late enhancer activation. These studies further revealed mechanisms by which non-coding genetic variation influences absolute levels of enhancer activity and their dynamic responses to IL-4, thereby contributing to strain-differential patterns of gene expression and phenotypic diversity.
Relationships between the Bone Expression of Alzheimer Disease-Related Genes, Bone Remodelling Genes and Cortical Bone Structure in Neck of Femur Fracture
Authors: Stapledon Catherine J.M. , Stamenkov Roumen , Cappai Roberto , Clark Jillian M. , Bourke Alice , Solomon L. Bogdan , Atkins Gerald J. 
Published: November 2020

AbstractNeck of femur (NOF) fracture is a prevalent fracture type amongst the ageing and osteoporotic populations, commonly requiring total hip replacement (THR) surgery. Increased fracture risk has also been associated with Alzheimer disease (AD) in the aged. Here, we sought to identify possible relationships between the pathologies of osteoporosis and dementia by analysing bone expression of neurotropic or dementia-related genes in patients undergoing THR surgery for NOF fracture. Femoral bone samples from 66 NOF patients were examined for expression of the neurotropic genes amyloid precursor protein (APP), APP-like protein-2 (APLP2), Beta Secretase Cleaving Enzyme-1 (BACE1) and nerve growth factor (NGF). Relationships were examined between the expression of these and of bone regulatory genes, systemic factors and bone structural parameters ascertained from plain radiographs. We found strong relative levels of expression and positive correlations betweenAPP, APLP2, BACE1andNGFlevels in NOF bone. Significant correlations were found betweenAPP, APLP2, BACE1mRNA levels and bone remodelling genesTRAP, RANKL, and theRANKL:OPGmRNA ratio, indicative of potential functional relationships at the time of fracture. Analysis of the whole cohort, as well as non-dementia and dementia sub-groups, revealed structural relationships betweenAPPandAPLP2mRNA expression and lateral femoral cortical thickness. These findings suggest that osteoporosis and AD may share common molecular pathways of disease progression, perhaps explaining the common risk factors associated with these diseases. The observation of a potential pathologic role for AD-related genes in bone may also provide alternative treatment strategies for osteoporosis and fracture prevention.