dataesr/scientific-paragraphs-categorization huggingface dataset:
This analysis was implemented with the lfmm R package  80  on genotype calls from the VQSR pipeline, considering SNPs with call rate of at least 70% across isolates and minor genotype frequency above 5%, using K = 3 for the latent factor accounting for underlying population structure. Analyses were run five times and P values were combined and adjusted as recommended  80. Gene identification and GO enrichment analysis. Annotation of the revised H. contortus genome is ongoing. Therefore, genes underlying major differentiation signals were inferred by searching for similarity between the region of interest (10 Kbp window for F ST analyses, 2000 bp region around XP-CLR hits) against the published V1 H. contortus genome assembly 14 using BLAST v2. 2. 25. Any genes falling within most probable blast hit coordinates were retrieved from the H.
contortus published assembly available from WormBase Parasite  75. This database was also used to retrieve C. elegans orthologs of positional candidate genes and H. contortus Gene Ontology (GO) terms. GO term enrichment analysis was run with the R topGO 81 package, considering nodes with at least 10 annotated genes. The "weight01" algorithm was used to account for existing topology between GO terms. This framework makes P value of one GO term conditioned on its neighbours, thereby correcting for multiple testing. Enrichment was tested by the Kolmogorov-Smirnov statistic applied to gene selection or F ST score accordingly. GO terms with P values below 1% were deemed significant. Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Acknowledgements J. A. C. , M. B. , N. H. and S. D. are supported by the  Wellcome Trust  via their core funding of the  Wellcome Trust Sanger Institute  (grant  206194 ) and by  BBSRC  grant  BB/ M003949/1. G. S. has received the support of the  EU  in the framework of the  Marie-Curie FP7 COFUND People Programme , through the award of an  AgreenSkills  (grant agreement no. 267196 ) and  AgreenSkills + fellowships  (grant agreement no. 609398 ). We are grateful to  Robin Beech  and  John Gilleard  for insightful discussions. Nematode material was provided by the  BRC4Env Animal Parasitic Nematodes collection , the environmental resources pillar of the AgroBRC-RARe research infrastructure.
A Corrigendum on Genetic and Phenotypic Characterization of the Etiological Agent of Canine Orchiepididymitis Smooth Brucella sp. BCCN84. 3 by Guzmán-Verri, C. , Suárez-Esquivel, M. , Ruíz-Villalobos, N. , Zygmunt, M. S. , Gonnet, M. ,  Campos, E. , et al. (2019 ). Front. Vet. Sci. 6:175. doi: 10. 3389/fvets. 2019. 00175 In the original article, there was an error. In the Funding statement is written that MZ was granted with a fellowship from SEP, Universidad de Costa Rica. The correct Initials are MS-E. A correction has been made to the Funding statement: This work was supported by FEES-CONARE, Costa Rica; Fondo Institucional de Desarrollo Académico (FIDA), Universidad Nacional; Wellcome Trust; CITA-INIA, Spain (project Bru-Epidia 291815-FP7/ERANET/ANIHWA); MINECO (AGL2014-58795-CA), and Aragon Government (Consolidated Group A14).
Publicly Available RNA-Seq and ChIP-Seq Reads This study is mainly based on publicly available data that were previously generated in our laboratory. Transcriptomic data (i. e. , total RNA isolation followed by single-read 50 nucleotides Illumina sequencing) for both sexes in cercariae, schistosomula (stage S#2), and immature worms were described in  Picard et al. 2016  (raw reads are available under accession number SRP071285 on NCBI-SRA database). As for epigenetic data (i. e. , chromatin immunoprecipitation, or ChIP, followed by single-read 50 nucleotides Illumina sequencing): H3K27me3 ChIP-Seq was analyzed in  Picard et al. 2016  (male data available under accession number SRP071285); H3K27me3, H3K4me3, and H3K20me1 ChIP-Seq in females were reported in  Roquis et al. 2016 and Roquis et al.
RNA-Seq Raw Read Processing Raw RNA-Seq reads were cleaned using trimmomatic v0. 3  (Bolger et al. 2014) , with the following options: SE -phred33 ILLUMINACLIP:$/Trimmomatic-0. 36/adapters/ TruSeq3-SE. fa:2:30:10 HEADCROP:12 LEADING:3 TRAILING:3 SLIDINGWINDOW:4:15 MINLEN:36. Resulting high quality reads were mapped to the S. mansoni reference genome v5. 2 obtained on the WormBase Parasite database (schistosoma_mansoni. PRJEA36577. WBPS9. genomic. fa, at https://parasite. wormbase. org/index. html; Last accessed June 27, 2019) using Tophat2  (Trapnell et al. 2009) , with the following options: -library-type fr-firststrand -microexon-search -i 10 -I 40000 -min-segment-intron 10 -max-segment-intron 40000. Mapped reads were counted using Htseq  (Anders et al. 2015) , with the following options: -f bam -s reversem union -idattr gene_id (see read counts in supplementary Data 1, Supplementary Material online).
Gene Expression Analysis According to Genomic Location Gene location was based on GTF annotations obtained at WormbaseParasite (schistosoma_mansoni. PRJEA36577. WB PS9. canonical_geneset. gtf, https://parasite. wormbase. org/index. html; Last accessed June 27, 2019). More precisely, genes located on the ZW sex chromosome linkage map were then attributed either to the Z-specific region or to pseudoautosomal regions (PARs) depending on their coordinates (Z-specific windows: Z1: 3,550,  000-13,340,000; Z2: 13,860,000-19,650,000; Z3: 23,230,000-30,820 ,000, supplementary Data 3, Supplementary Material online)  (Protasio et al. 2012). Normalized expression data combined to gene locations were then implemented into an R script for drawing gene expression patterns (supplementary Data 4, Supplementary Material online).
This R script is available as supplementary Methods 1, Supplementary Material online. Briefly, a Loess Normalization (R library Affy) was performed, taking into account the 12 libraries (cercariae, schistosomula, immature worms, for both sexes, and in duplicate). For each sex and stage, the averaged expression was then considered. Different thresholds for minimum of expression level were applied (RPKM > 0, RPKM > 1, and RPKM > 5), and strong sex-bias were considered or not. These strong sex-bias were defined by a fold change higher than 2, considering either the female-to-male ratio (female sex-bias), or the male-to-female ratio (male sex-bias). When comparing two conditions, the ratio between the medians of expression was calculated, and the level of significance was tested with Wilcoxon rank sum tests with continuity correction.
Acknowledgments The authors thank the  Tecnoviv platform at UPVD (Perpignan, France)  and IT support at  IST Austria (Klosterneuburg, Austria)  for providing optimal environment to perform highthroughput sequencing data analysis. This project was funded by the  R egion Languedoc Roussillon (France) :  Schistosex  ( 2012 , to J erome Boissier) and Transgigas (2015, to C eline Cosseau) "chercheur d'avenir" grants. The authors declare that they have no conflict of interest.
NOTE. -RNA-Seq and ChIP-Seq data were previously generated in our laboratory and were published in two different studies: SRP071285 accession number (SRA-NCBI database) for RNA-Seq and male H3K27me3 ChIP-Seq duplicates (Picard et al. 2016) ; and SRP035609 accession number (SRA-NCBI database) for female ChIP-Seq triplicates (Roquis et al. 2016 ). H3K4me3 ChIP-Seq analysis on males was never presented before and was deposited under SRP071285 accession number (SRA-NCBI database).
Acknowledgments The authors thank  Doctor Pascaline Pey , DVM, PhD, DECVDI, for the interpretation of the images and  Professor Barbara M. Kirby , DVM, MS, DACVS, DECVS, for assisting to the preparation of the article. This case report was presented as a poster at the 25 th ECVS Annual Scientific Meeting in Lisbon, Portugal, on July 7-9, 2016, and as a short communication at the 8th HCAVS Forum, in Athens, Greece, on March 2017.
Results Twenty-five dogs aged from 2 to 12 years old and weighing from 10 to 56 kg were included in the study (Table  1 ). All dogs included in groups B and C presented radiographic and clinical signs of OA, without any statistical difference between groups. Affected joints included bilateral hips (n = 6), right stifle (n = 5), bilateral hips and shoulders (n = 4), bilateral hips and right or left elbow (n = 3), bilateral elbows (n = 1) and right shoulder (n = 1). Clinical signs as reported by the owners started between 1 and 12 months prior to inclusion in the study. The following breeds were represented: Labrador Retriever (n = 7), German Shepherd (n = 7), Rottweiler (n = 3), Boxer (n = 1), Fawn Brittany (n = 1) and Fox Terrier (n = 1). At D0, there were no statistical differences among the 3 groups with regards to gender, age, standard laboratory analyses (complete blood count (CBC) including white blood cells differential countdata not shown -, renal and hepatic profile), and platelet aggregation, GI endoscopic score and GFR (Table  1 ).
Statistical analysis Data was analyzed using SPSS software (IBM Corp. released 2011, IBM SPSS Statistics for Windows, Version 20. 0, Armonk, NY: IBM Corp. ). Data were analyzed with a general linear mixed model for repeated measures, with two-tailed testing and an alpha value set at 0. 05. Adjustment for multiple comparisons was applied when necessary. The model included the fixed effects of treatment, time point, and interaction between treatment and time point. The random effects included animal, treatment, and error. The best covariance structure (compound symmetry) was chosen according to Akaike information criterion. Change over time was detected by testing for within-time group variation, and treatment effect was detected by significant change over time for groups A, B and C. If any treatment-related effect was significant, pairwise treatment comparisons were done at each time point.
Molecular techniques enable researchers to differentiate cryptic species that are morphologically similar at the larval or adult stages  [14, 20]. These molecular tools have great discriminatory power, but (i) they are still sometimes technically challenging and remain time-and resource-consuming, and (ii) GenBank does not include sufficient sequences to allow for strong species identification, especially sequences obtained from adults (except for the most common parasites of human and veterinary importance). Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) is now a widely used technique for easy, rapid, and reliable routine identification of bacteria and yeasts  [5, 31, 34]. This technique is based on laser ionization of sample proteins after co-crystallization with MALDI-matrix and comparison of the obtained mass spectra with a database of reference spectra  [5].
MALDI-TOF MS Spectral acquisition To achieve MALDI-TOF spectral acquisition, 2-5 lL of water containing freshly emerged cercariae was directly spotted to the MALDI target or centrifuged at 4000 rpm for 3 min. After centrifugation, the pellet was washed with distilled water and 5 lL was spotted onto the MALDI target plate (Bruker Daltonik GmbH, Bremen, Germany). Each sample was deposited in at least four replicates. After drying at room temperature, the samples were covered with 1 lL of 70% formic acid. After complete drying, 1 lL of matrix (a-cyano-hydroxy-cinnamic acid in solution with 2. 5% trifluoroacetic acid and 50% acetonitrile in water, Bruker Daltonik) was added to each spot. The target was then air-dried at room temperature. MALDI-TOF spectrum acquisition was performed using a Microflex LT mass spectrometer controlled by FlexControl software (Bruker Daltonik) with detection of positive ions on a range of 2000-20,000 m/z (mass to charge ratio).
Each spectrum was acquired from 240 laser shots on random regions of the spot using autoexecute mode. Instrument calibration was verified using the Bacterial Test Standard (Bruker Daltonik). Spectra were processed using the FlexAnalysis and MALDI-Biotyper v3. 4 software suite (Bruker Daltonik). High quality spectra for each sample were selected to create reference spectra (Main Spectrum Profile: MSP) using the default Bruker Method, which were added to the in-house database. Hierarchical cluster analysis (MSP dendrogram) was performed on the newly created MSP using MALDI-Biotyper Compass Explorer v4. 1 software, and a distance matrix was calculated using the correlation method and clustered with the Ward algorithm.
Database validation and LSV cut-off determination The newly created MSP database was evaluated by means of a blind test performed with new specimens from the DR lake. These new specimens were also deposited in four replicates and each spot was acquired 12 times. The log-score value (LSV) calculated by the Bruker MALDI-Biotyper was then used to evaluate the reliability of species identification based on the similarity between the reference MSP and newly acquired spectra. The cut-off for LSV was determined on the basis of molecular identification using a receptor-operated-channel curve (ROC curve) calculated by logistic regression (SAS 9. 4, Grégy-sur-Yerres, France).
Evaluation of the effect of storage in ethanol In a first step, the specimens of the validation set stored in 80% ethanol were re-analyzed by MALDI-TOF 3 months (91 days) later, using the same parameters. In a second step, specimens preserved in ethanol over a period ranging from 1 to 14 months were analyzed by MALDI-TOF. In order to evaluate the effect of ethanol fixation, some specimens were fixed in ethanol immediately after emission and analyzed by MALDI-TOF MS the same day. Differences between true positive rates and LSVs were analyzed using Chi-Square and ANOVA tests (SAS 9. 4, Grégy-sur-Yerres, France).
with LF; 38 Planorbis sp. , 36 with LF, and two with Echinostomatidae (Table  2 ). Twelve taxa were identified according to the domains used (D2, ITS1 et ITS2) and after comparison of their percentage of homology with sequences deposited in GenBank: FO: Trichobilharzia anseri; LF: Diplostomum pseudospathaceum, Tylodelphys sp. , Australapatemon sp. , Cotylurus sp. , Posthodiplostomum sp. , Parastrigea sp. , Alaria alata; EC: Echinostoma revolutum, Petasiger phalacrocoracis, Echinoparyphium sp. ; XI (Plagiorchis sp. ) ( Consistent and reproducible MALDI-TOF MS spectra were acquired from all the specimens, except for LFDC96 (Parastrigea sp. ) with peaks of high intensity between 2 and 20 kDa. All the 12 taxa from which spectra were acquired displayed different peak patterns (Fig. 1 ). Spectra were tested against the Bruker Taxonomy MSP library, providing no bacterial or fungal identification with log-score values > 1.
5. The results of MSP cluster analysis are shown in Figure  2A. Specimens of the same species were grouped together in clusters clearly separated from other species, with low intra-species heterogeneity. Furcocercariae with forked tails without pigmented eye spots were particularly distant from the other cercariae. The classification is consistent when compared to that based on molecular data inferred using the maximum likelihood method (Fig. 2B ). The MSP database constructed with 10 species (20 MSP) was blind-tested against spectra acquired from 22 samples of freshly emitted cercariae representing five species. Among them, three species were present in the database (Alaria alata n = 15/ 22, Australapatemon sp. n = 1/22, and Echinoparyphium sp. n = 1/22). Among the 1056 acquisitions, 264 spectra (25%) were flat-line spectra and were therefore not included in the analysis.
In the 792 remaining spectra, 648 were acquired from species present in the database. Among them, only 147/648 (22. 68%) reached the Bruker recommended cut-off LSV of 2. 0 for species level identification. However, an LSV of 1. 7 sufficient for genus identification was obtained in 443/648 spectra (68. 36%). In order to evaluate the best LSV cut-off for cercariae identification, a logistic regression model, based on concordance of MALDI-TOF and molecular data was then built. The ROC curve is shown in Figure  3. The area under the curve of the model was 0. 9501 (95% Wald confidence limits: 0. 9357-0. 9644). Choosing an LSV threshold of 1. 7 enabled us to obtain specificity of 100%, with sensitivity of 81. 7% (Fig. 3 ). No false identification was reported using 1. 7 and 2. 0 cut-off LSV, even for the taxa which were not present in the database, 108 spectra of Cotylurus sp.
(LFDC43, LFDC88, LFDC89, LFDC90, LFDC91) and 36 spectra of the Posthodiplostomum sp. (LFDC83). The database was then updated to include Cotylurus sp. with MSPs generated from LFDC89 and LFDC90. This new version yielded good performance for species identification of Cotylurus sp. (78 correct identification among the 78/108 spectra attaining the LSV cut-off of 1. 7). This updated database had similar performances with 521/792 spectra reaching the 1. 7 cut-off (65. 78%), with 100% correct identifications. Retrospectively, we did not observe any differences in terms of spectral profile between cercariae of the same species from one year to the next. For example, spectra of Alaria alata isolated at Chambord (LFDC41/44/45/50/51/52/53/54) in 2017 did not differ from those isolated in 2018 (LFDC57-LFDC72).
Among the 1114 spectra acquired, 553 (49. 64%) were flatline spectra. In the 561 spectra analyzed using the updated database, 183 reached the cut-off LSV (32. 62% vs 65. 78% without ethanol p < 0. 0001). The mean LSV was 1. 80 (Median: 1. 93; Min: 0. 13; Max: 2. 77) for freshly emitted cercariae versus 1. 62 (Median: 1. 71; Min: 0. 43; Max: 2. 48; p < 0. 0001) for cercariae preserved in ethanol. Interestingly,   there was no false identification for the 183 spectra preserved in ethanol attaining the 1. 7 cut-off. In a second round, we analyzed the effect of exposure time to ethanol on collected samples and freshly emitted samples. Among the 1074 spectra (including the 561 previously described), 287 (26. 72%) reached the 1. 7 LSV cut-off (all of them were concordant with molecular identification).
0 were considered valid at the genus level, and LSVs higher than 2. 0 were considered reliable identification at the species level. In our study, using an LSV cut-off of 2. 0 for identification at the species level was highly specific, but resulted in a high proportion of unidentified spectra. Lowering the cut-off to 1. 7 allowed for the identification of a higher number of specimens with similar specificity. This cut-off value has already been proposed for species-level identification of filamentous fungi  [4, 29]. Further studies are needed for the validation of this cut-off on upgraded spectral databases with a higher number of taxa. In our study, we observed a high proportion of "flat-line" and low-quality spectra. These can be explained by the heterogeneity of the cercariae deposited in the MALDI-TOF target.
This raises a problem for the retrospective study of collections stored in ethanol. The study of other storage methods for the biological material, such as freezing at different temperatures and other fixatives, seems important for the development of this technique. We constituted for this study an MSP database with a limited number of Trematoda species. It must be improved by inclusion of new species to cover the broad range of Trematoda involved in veterinary or human medicine. The database would also be improved by increasing the number of strains for a given taxa  [30]. Our study highlights the huge potential of MALDI-TOF for large epidemiological surveys of Trematoda. This technique could thus be applied to the study of human schistosomiasis, including the detection of hybrids  [3, 8, 24] , allowing for rapid and precise identification of the cercariae obtained during large snail collection campaigns.
Acknowledgements. Financial support for this study was provided through a research agreement between  Hubert Ferté  and  ONCFS (French game  and wildlife agency including the SAGIR network), and partially by the  ARS  (regional health agency) of Burgundy. We would like to thank the technical staff of the national domain of  Chambord (Etienne Guillaumat, Philippe Hubert, Pascal Blondeau ), the technical staff of the national reserve of Der-Chantecocq lake ( Yves Maupoix ), and  Mrs Leroux  for their hospitality during snail collection. We also thank  Mireille Cousinat  and  Denis Augot  for their technical assistance, as well as  Matthieu Kaltenbach  for proofreading this manuscript.
Therefore, delafloxacin efficiency in community-acquired pneumonia has been evaluated in recently completed Phase 3 study (NCT02679573). Ceftobiprole medocaril, an anti-MRSA cephalosporin indicated for the treatment of complicated skin infections and community/hospital acquired pneumonia, it is still unapproved by the FDA, but currently used in some European countries and in Canada  59. The new lipoglycopeptide dalbavancin -FDA approved for acute bacterial skin and skin structure infections -has a high microbiological activity against staphylococci and enterococci. Moreover, dalbavancin has long half-life (up to 250 hours), which makes it a suitable option for a more rapid hospital discharge. However, a Phase II study which aimed to evaluate the effectiveness of dalbavancin in patients with blood stream infections or infective endocarditis was stopped early due to economic reasons (NCT03148756) and data are insufficient to support its use in this setting  60, 61.
The ELISA signals obtained from non-affinity matured clones that showed a binding profile on yeast similar to that of the parental antibody M3_B11, were similarly low or even worse (data not shown). We performed an additional ELISA assay to ascertain whether the antibodies were able to bind to mycolactone that was not biotinylated. The results showed a very similar pattern to those obtained previously using biotinylated antigens (Figure  5 ). Antibodies also showed no binding to ubiquitin or LPS, used as negative controls, and directly coated to the ELISA plate. control. * Indicates a p value < 0. 05 compared to the parental clone. We performed an additional ELISA assay to ascertain whether the antibodies were able to bind to mycolactone that was not biotinylated. The results showed a very similar pattern to those obtained previously using biotinylated antigens (Figure  5 ).
Next-Generation Sequencing The VH regions of the antibodies obtained after Selection 2 were amplified with specific primers and submitted for Illumina MiSeq 2 × 250 bp sequencing (SeqMatic, Fremont, CA, USA). The CDR regions of these clones were identified using IgBlast. For HCDR3 analysis, in-house scripts were developed using Python3. 7. Levenshtein distance was calculated using the package 'distance' and was normalized by the length of the smallest sequence. Sequences with less than 30% distance were clustered. Principal component analysis was performed using the function implemented at the package 'scikit-learn'.
Real-time PCR (qPCR, for quantitative PCR) presents the advantages of faster data collection than classical PCR, low contamination risks and high sensitivity. Several qPCR assays that target the tox gene have been described  [22] [23] [24] [25]  Here, we aimed to address this limitation by replacing the gfp target gene by a universal fragment of the 16S rRNA (u-16S) gene sequence to serve as an internal processing control. Further, we aimed to validate the improved qPCR assay directly on clinical specimens such as throat swabs and pseudomembrane biopsies. Additionally, we tested the characteristics of the modified quadruplex qPCR assay including specificity, sensitivity, reproducibility, experimental robustness and its implementation on distinct qPCR apparatuses and in separate laboratories.