dataesr/scientific-paragraphs-categorization huggingface dataset:
Ortholog search strategy The detection of ortholog sequences in the combined genomic and EST data sets followed two sequential approaches. First, orthology relationships among 488,087 protein sequences for the 37 Basidiomycota species with complete draft genomes were assessed using the OrthoMCL software  [32]. The procedure starts with all-vs-all BLASTp comparisons, for which an e-value cut-off of 1e-5 was chosen. Then, a Markov Clustering (MCL) algorithm (http://micans. org/mcl/) [33, 34]  was used to create clusters of putative orthologs and coorthologs according to an inflation parameter that controls cluster tightness. To strike a balance between cluster tightness and the probability of breaking up clusters with the same orthologs, the intermediate inflation value of 3 was used. Since the output of OrthoMCL contains recent paralogs in addition to single copy genes, clusters with more than one gene copy per species or comprising less than 9 species out of the 37 total species were removed.
Furthermore, we only included single-copy genes represented by at least one species of the Pucciniales. This resulted in a final data set of 1,715 core single-copy ortholog clusters, 1,250 of which contained the three Pucciniales (S2 Table ). Nine additional Ascomycota species were added for outgroup purposes. For future reference in this paper, ortholog clusters will be simply referred to as genes. Second, the taxonomic coverage of the previously determined core single-copy genes was then expanded with EST data using the software HaMSTr  [35]. By complementing only this set of genes, we attempted to substantially reduce the chance of inadvertently introduce paralogs from the EST data. Each core gene was aligned in MAFFT v7. 0  [36]  using the L-INS-i method and Hidden Markov Model profiles were then constructed for each alignment using hmmbuild, included in the HMMR3 package (http://hmmer.
janelia. org) [37]. All 37 Basidiomycota species were used as representatives during the HaMSTr searches and the "-relaxed" option of the program was specified, in order to relax the constraint of a potential ortholog to be present in all representative species. Finally, species whose data could not complement at least 50 core genes were discarded, resulting in a final inclusion of 21 species with EST sequences. Therefore, the largest data set assembled contained genomic data from 37 Basidiomycota species, 9 Ascomycota species and EST data from 21 additional species, for a total of 67 species.
Sequence alignment and filtering Genes were aligned with MAFFT v7. 0 using the L-INS-i method. Alignment columns with excessive missing data were filtered by a custom python script, which removed columns with a proportion of missing data above 50% in the extremities of the alignment and columns with a proportion of gaps and missing data above 75%. In order to take the alignment uncertainty into account when performing the phylogenomic reconstruction, weights were attributed to each alignment column, using the probabilistic framework implemented in ZORRO  [38] , for latter interpretation by the phylogenetic reconstruction software. For the detection of positive selection, the DNA sequences corresponding to each species in the protein alignments were assembled and aligned with TranslatorX  [39]  using the protein alignment as reference.
Since the software used to detect positive selection does not incorporate the probabilistic weighting schemes from ZORRO, filtering of fast evolving and potentially misaligned alignment blocks was performed following two independent approaches: Guidance  [40] , using default parameters and MAFFT as the multiple sequence alignment algorithm, and Gblocks  [41] , within the framework of TranslatorX, using default parameters, except that columns with half gap positions were allowed (option -b5 = h).
Assessment of gene molecular rates In parallel to the genome-wide screening of positive selection, the evolutionary rate of the genes with highest taxa representation in the genomic46_dense data set, was assessed for several branches of the Pucciniales by fitting a relaxed molecular clock to the data using the MCMCTree software, included in the PAML 4. 7 package  [46]. The phylogenetic tree resulting from the phylogenomic analyses was used as input for all alignments. Since not all species were present in all alignments, the input phylogenetic tree for each alignment was pruned according to the present taxa, with the condition that all representative species of the Pucciniales had to be included. If this condition was not verified, the alignment was discarded from the analysis. Since the approximate method of MCMCTree was mandatory for protein alignments, maximum likelihood estimates of branch lengths, the gradient vector and Hessian matrix were initially calculated using the Codeml program using the WAG+Γ 4 substitution model.
Functional annotation To gain insight on the functions of both the putative positively selected and genes under accelerated evolution, a functional annotation was performed using the euKaryotic Orthologous Group (KOG) terminology, according to the eggNOG 4. 0  [48]  database and using its BLASTbased online search tool (http://eggnog. embl. de). Additionally, a Gene Ontology enrichment analysis was performed to determine if any category was overrepresented for genes under positive selection and faster evolutionary rate. Statistically significant enrichment was tested against a reference of all genes analysed using the Fisher's exact test and a p-value for the independence of rows and columns in a 2x2 contingency table was computed. Significance was considered for p < 0. 10. To collect a more detailed information on those genes, sequence homology searches were performed against several databases: the NCBI non-redundant (nr) nucleotide and protein databases (www.
ncbi. nlm. nih. gov), the genome sequences of Melampsora larici-populina, Puccinia graminis f. sp. tritici and Uromyces fabae  [23, 49]  and the Pathogen-Host Interaction (PHI-base v3. 2) reference database (  [50] ; www. phi-base. org). BLAST searches were conducted with an e-value cut-off of e -5 , and only the best hit was considered.
Since the same gene can have positively selected sites from both classes, a distribution of the most prevalent site class per gene is presented in Fig 3. While Unique sites account for the majority of selected sites in both data sets, the advantage is less pronounced in the basidioPAML_Hv data set. Comparing both data sets 75 genes had signatures of positive selection in both data sets, while 253 genes were exclusive from the basidioPAML data set and 29 were exclusive from the basidioPAML_Hv data set. A database containing information about the PAML tests for each alignment, including the position and number of selected sites is provided in S3 Table.
Functional annotation and enrichment Overall, 357 unique genes (75 shared by both data sets, 29 exclusive from the basidioPAML_Hv data set and 253 exclusive from the basidioPAML data set) were detected as being under positive selection in either foreground branches. Functional annotation of these 357 genes was obtained using the KOG terminology (S4 and S5 Tables). Over 82% (292) of the positively selected genes were classified into 21 specific KOG categories, while 10% (36) had no specific KOG category assigned ["Function unknown"  (13)  or "General function prediction only"  (23) ], and 8% (29) had no hits. Considering the proportion of genes under positive selection against the respective reference of all orthologs analysed, statistical analysis of the under or overrepresentation of the targeted genes for the basidioPAML revealed a relative enrichment (over 1.
5 fold change) in genes annotated into "Secondary metabolites biosynthesis, transport and catabolism", "Amino acid transport and metabolism", "Coenzyme transport and metabolism" and "Nuclear structure", and an impoverishment (less than 0. 67 fold) in genes annotated into "Chromatin structure and dynamics", "Signal transduction mechanisms" and "Cytoskeleton" (S3 Table ). However, the Fisher's exact test revealed that only the "Amino acid transport and metabolism" functional class was significantly enriched in positively selected genes. For the basidioPAML_Hv dataset, KOG annotation relative enrichment (over 1. 5 fold change) was found in genes as assigned to "Secondary metabolites biosynthesis, transport and catabolism", "Energy production and conversion", "Lipid transport and metabolism" and "Amino acid transport and metabolism", as well as an impoverishment (less than 0.
67 fold) in genes annotated as "Inorganic ion transport and metabolism", "Transcription", "RNA processing and modification", "Intracellular trafficking, secretion, and vesicular transport", "Signal transduction mechanisms" and "Cytoskeleton", (Fig  4 ). However, no functional classes were significantly over or under represented in this data set according to Fisher's exact test. To allow a direct comparison between the basidioPAML and basidioPAML_Hv data sets, we performed the same enrichment analysis for the basidioPAML data set with the 531 non-saturated shared genes among data sets as reference in order to account for differences within the same universe of reference genes. Similarly to the respective whole set of orthologous, genes annotated as "Secondary metabolites biosynthesis, transport and catabolism" and "Amino acid transport and metabolism"were enriched as well as genes from the "Carbohydrate transport and metabolism" class.
Genes annotated as "Replication, recombination and repair" and "Cytoskeleton" were also found to be impoverished, in addition to "Intracellular trafficking, secretion and versicular transport". Fisher's exact test reported a statistically significant enrichment of the "Amino acid transport and metabolism" functional class as for the complete basi-dioPAML data set, but further revealed a significant enrichment of 'Carbohydrate transport and metabolism' and impoverishment of 'Signal transduction mechanisms'. Among the studied 985 genes, 249 blasted with genes involved in pathogenicity at PHIbase. Out of the 328 positively selected genes in the basidioPAML, 93 presented homology with entries in the PHI-base as well as 35 out of the 104 genes under positive selection in the basidio-PAML_Hv. In both data sets, the Fisher's exact test revealed that positively selected genes were  enriched for PHI-base assigned genes putatively involved in pathogenicity, with p-values of < 0.
Genome-wide scan for positive selection After establishing a backbone phylogeny for the studied Basidiomycota, up to 985 non-saturated genes were screened for signatures of positive selection using the branch-site model. This method revealed to be particularly well suited for our investigation, as it is capable of detecting episodes of positive selection specifically on the root branch of the Pucciniales. An analysis pipeline was then constructed to perform a genome scan on two different but related data sets. The basidioPAML data set included 985 genes solely retrieved from complete draft genomes but did not include H. vastatrix. From those 985 genes, the basidioPAML_Hv data set consisted in a sub-sample of 531 genes that could be complemented with EST data from H. vastatrix. Therefore, even though our pipeline analyzed the root branch of the Pucciniales in each data set, they represent distinct evolutionary periods, with the basidioPAML_Hv data set providing the most ancient branch but also significantly less data than the basidioPAML data set.
Both data sets presented an impressively high proportion of positively selected genes, suggesting an unexpectedly pervasive role of positive selection shaping the origin of rust fungi: 328 genes (33. 3%) showed signatures of positive selection in basidioPAML as compared to 104 genes (19. 6%) in basidioPAML_Hv. Even when the same alignments were filtered with Gblocks, which is known for its aggressive removal of alignment columns and consequent reduction in power to detected sitewise positive selection, the number of positively selected genes remained high [216 genes (21. 9%) for basidioPAML and 100 genes (18. 8%) for basidioPAML_Hv]. Studies that employ genome scans to search for positive selection using the branch-site model are numerous but they generally present lower proportions of genes under positive selection.
For the basidioPAML data set, 2,067 sites were detected to be under positive selection across 274 genes (27. 8%), as compared to the 289 sites across 72 genes (13. 6%) on the basidioPAML_Hv data set. While the lower proportion of positively selected genes and sites in the latter data set may be attributed to biologically relevant differences that arise from studying different foreground branches, this may also be a reflection of differences in the composition of the data sets, such as the average gene length reduction in the data set containing H. vastatrix, as regions with potentially selected sites may not be present in the sequences of this species. We then explored the profile of the selected amino acids by sorting them among two main site classes: Unique and Diversifying. By establishing these classes, the aim was to shed light on the adaptive role of the selected sites and how they may have contributed to the evolution of rust fungi.
Unique and Diversifying positively selected sites are potential prime candidates for adaptive drivers underlying the initial divergence and adaptation of rust fungi, but their distinction may be key to distinguish between adaptations that are important for all rust species and remain unchanged throughout their evolution and adaptations that later diversified in different terminal branches of the Pucciniales. Most of the positively selected sites showed a Unique class pattern in both data sets, though its proportion decreases in the basidioPAML_Hv data set, with the inclusion of the ancient H. vastatrix branch, which is also reflected on the prevalence of each site class in the positively selected genes. This result is expected because the basidioPAML_Hv data set includes more divergent species, but it also stresses the importance and impact of including an ancient lineage when studying the evolutionary history of a taxonomic group.
In either case, this seems to reveal that adaptive changes that occur at the root of the Pucciniales are more likely to remain conserved across all rust species possibly in order to conserve a newly acquired adaptive trait. On the other hand, some positively selected sites were subject of further modification since the origin of rust fungi and may be responsible for species or genus specific alterations, although it cannot be concluded whether such modification was due to a relaxation of selective pressure or continuous action of positive selection. Nevertheless, our results show that 95% and 91% of the positively selected genes in basidioPAML and basi-dioPAML_Hv data sets, respectively, contain both Unique and Diversifying sites, suggesting that natural selection may shape the same gene in different ways with potentially different outcomes during the evolution of a species group.
Assessing the evolutionary rate on the origin of Pucciniales To further investigate the evolutionary rate on the basal branch of the Pucciniales, we assessed the substitution rate on that specific branch across the 612 genes with the highest taxa representation in our data set, including all three Pucciniales species with complete genomes. Hemileia vastatrix was not included because the fragmented and overall lower quality nature of the EST data could bias estimates of substitution rates and produce misleading results. On average, the molecular rate of the root branch of the Pucciniales seems to be evolving on par with the average molecular rate of all other branches in the tree, but a significant heterogeneity in the substitution rates was also present, with a strong bias towards fast evolving genes since all outlier genes were evolving more rapidly.
Functional enrichment analyses The impact of studying different foreground branches that span different time periods between the basidioPAML and basidioPAML_Hv data sets was further explored by investigating the enrichment of functional classes for the positively selected genes in each data set. Given the substantial overlap of positively selected genes between data sets (75 genes), the enriched functional classes were also found to be similar. The metabolic related classes of "Amino acid transport and metabolism" and "Secondary metabolites biosynthesis, transport and catabolism" were found to be the most enriched for positively selected genes in both data sets, with the first mentioned class showing statistical significance in the basidioPAML data set. When comparing directly these data sets at the level of the 531 shared genes, we found that the "Carbohydrate transport and metabolism" class was also significantly enriched for the basidioPAML data set.
Acknowledgments We are grateful to  F. Martin  and the  Mycorrhizal Genomics Initiative consortium  for access to unpublished genome sequence data of Hebeloma cylindrosporum and Paxillus involutus, produced by the  US Department of Energy Joint Genome Institute  in collaboration with the user community. Likewise, we thank  Dan Cullen ,  David Hibbett  and  Igor Grigoriev  for granting permission to use unpublished genome data of Phlebiopsis gigantea and Sporobolomyces roseus, sequenced by the  US Department of Energy Joint Genome Institute. Finally, we thank the PIs of Puccinia triticina genome project,  Christina Cuomo ,  John Fellers ,  Guus Bakkeren ,  Les Szabo ,  Xianming Chen  and  Scot Hulbert , for access to the unpublished sequence data from the  Broad Institute.
The project was funded by project grant  PTDC/AGR-GPL/119943/2010  from the  Fundação para a Ciência e Tecnologia (FCT)  (http://www. fct. pt/) and by  FCT Unit  funding  UID/BIA/00329/2013. DNS acknowledges the  FCT grant   SFRH/BD/86736/2012. SD acknowledges the  Agence Nationele de la Recherche (France)  " Investissements d'Avenir" program  ( ANR-11-LABX-0002-01 ,  Lab of Excellence ARBRE ). PT acknowledges the  FCT grant   SFRH/ BPD/88994/2012. DB acknowledges the  FCT grant   SFRH/BPD/104629/2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
A Zenodo repository (DOI: 10. 5281/zenodo. 30970) was created to archive the following data: (i) all alignments for each data set in Table  1 ; (ii) The alignments, control files and tree files for the PAML analysis; (iii) The control files and tree files for the MCMCTree analysis. All relevant python scripts are available at the GitHub repository https://github. com/ODiogoSilva/Silva2014_ RustPhylogenomics.
ACKNOWLEDGEMENTS The work of GC was supported by the  National Science Foundation Graduate Research Fellowship  under Grant No. DGE1322106. The work of DL was supported in part by the  John Simon Guggenheim Memorial Foundation  and by the  National Science Foundation  under Grant No. DMS-0758374. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the  National Science Foundation. FN thanks all the members of the clinical and routine laboratory teams for the valuable and continuous work for the care of our patients, the association " Regarde un jour le monde"  for its support and patients themselves for participating in this study.
METHODS The French Society of Rheumatology and the Club Rhumatismeet Inflammations have set up the AutoImmunity and Rituximab (AIR) registry. The AIR registry is a multicentre prospective cohort designed to study the safety and efficacy of RTX in the treatment of RA and other refractory AIDs. Follow-up data are collected every 6 months over 7 years. Serious adverse events, including serious infections (requiring hospitalisation and/or intravenous antibiotics), cancers and deaths, are validated by the two coordinators of the registry using chart copies. The methodology of the registry was reported previously. 16 17 This study was approved by the French authorities Comité Consultatif sur le Traitement de l'information en matière de Recherche dans le domaine de la Santé and Commission Nationale de l'Informatique et des Libertés.
Written informed consent was obtained from all patients. Neutropenia is defined by an absolute blood neutrophil count less than 1500/mm 3. Neutrophil count was requested at inclusion and at each follow-up visit (3 months, 6 months then every 6 months, or at any time in case of treatment change). Late-onset RTX-related neutropenia was defined as an absolute neutrophil count of ≤1. 5×10 9 /L starting from 4 weeks after termination of RTX therapy until 12 months after the last RTX infusion. 2 eutropenia prior to RTX and other drug-related neutropenia were excluded. At each visit, the crf includes specific questions regarding the potential complications of neutropenia. For each episode of neutropenia, data were abstracted from the electronic crf, validated and completed if necessary, using a specific questionnaire, by the clinician in charge of the patient.
Statistical analysis Patients contributed person-years of follow-up between the first infusion of the first cycle and death, or the last follow-up visit. For the incidence rate calculation of neutropenia, the time of neutropenia was used as the right censoring rule. Rates of neutropenia are presented as event/100 patient-years. Data are presented as median (IQR) for quantitative values and proportions for qualitative values. All analyses were performed using SAS software V. 9. 3 (SAS system SAS Institute, Cary, North Carolina, USA). In univariate analysis, a χ 2 test or Fisher's exact test was used for qualitative data according to application requirements. A non-parametric Mann-Whitney U test was used for quantitative values. A p value <0. 05 was defined as significant.
Acknowledgements  Roche  provided an unrestricted educational grant to the French Society of Rheumatology but was not involved in the design, protocol, data collection or statistical analysis of the study. The authors thank all the investigators who have included patients in the AIR registry, the  French Society of Rheumatology (SFR) , the  Club Rhumatismes et Inflammation , the  French National Society of Internal Medicine (SNFMI)  for their implication in the AIR registry,  Rosemary Jourdan  ( Roche ),  Jamila Filipecki  and  Nadine Mackenzie  (formerly  Roche ). They also thank the 14 research study nurses ( A Bourgeois ,  E Braychenko ,  F Carmet , MH  Da Silva ,  S Delmas ,  D Guinement ,  R Lefebure ,  C Lehning ,  N Minot ,  FMA Ouattara ,  V Pinosa ,  M Reau ,  H Thibault  and  E Wallet ),  L Dongmo  and  V Martin , all working in Euraxipharma, the contract research organisation in charge of data collection in the AIR registry.
Acknowledgements Z. Cs. -S. was supported by  National Research Council of Romania  grants  CNCSIS 1930/2008  and  CNCS PN-II-ID-PCE-2011-0381 , and by the  University of Bucharest  (project  1001/2012 ). E. B. thanks the  Association Culturelle, Archéologique et Paléontologique de l'Ouest Biterrois , the  Aix-en-Provence Natural History Museum , the  Toulon Natural History Museum , and the  Espéraza Dinosaur Museum  for their.
Background: The purpose of this study was to examine the association between mental health status (i. e. depressed mood and pregnancy-related worries) and objectively measured physical activity levels in obese pregnant women from seven European countries. Methods: Baseline data from the vitamin D and lifestyle intervention for the prevention of gestational diabetes mellitus (DALI) study were used. Time spent in moderate-to-vigorous physical activity (MVPA) and sedentary behaviour was measured with accelerometers. Depressed mood was measured with the WHO well-being index (WHO-5) and pregnancy-related worries with the Cambridge Worry Scale (CWS). In addition, socio-demographic characteristics, lifestyle factors, and perceptions and attitude regarding weight management and physical activity were measured.