dataesr/scientific-paragraphs-categorization huggingface dataset:
Density and box plots were used to compare the means between both treatments. In addition, the changes due to A. brasilense inoculation on the hybrid traits were calculated by Δ = M1-M2, where M1 is the adjusted mean under N stress plus A. brasilense and M2 is the adjusted mean under N stress. Population structure was estimated by principal component analysis (PCA) using the genomic matrix through the SNPRelate R package  [48]. The GWAS analyses were conducted by a Fixed and Random Model Circulating Probability Unification method thought the FarmCPU R package  [49]. This statistical procedure considers the confounding effect between the testing marker and both kinship (K) and population structure (Q) as covariates to minimize the problem of false positive and false negative SNPs. The FarmCPU R package uses the FaST-LMM algorithm to calculate the K from selected pseudo-QTNs (Quantitative Trait Nucleotides) and not from the total SNP set, as the standard K.
On the other hand, in the heterozygous (dis)advantage GWAS model, the homozygous genotypes (A 1 A 1 or A 2 A 2 ) were assumed to have the same effect, while the heterozygous genotypes a different one, implying an increase or decrease of the effect on the trait. Therefore, the SNP matrix was coded by 0 (A 1 A 1 ), 1 (A 1 A 2 ), and 0 (A 2 A 2 )  [33, 34]. Box plots were then used to show the phenotype values by genotypes of the SNPs significantly associated with the traits. The average linkage disequilibrium (LD) in the hybrid panel was investigated using the square allele frequency correlation coefficient r 2 between all pairs of SNPs across the chromosomes using PLINK v. 1. 9 software  [50]. The extension of LD decay was verified by plotting the r 2 values against the physical distance of the SNPs.
Identification of candidate genes The candidate genes associated with the significant SNPs were obtained from the B73 genome reference (version 4) in the MaizeGDB genome browser (https://www. maizegdb. org/). Complementary information was collected from the U. S. National Center for Biotechnology Information (http://www. ncbi. nlm. nih. gov/) and the Universal Protein Resource (http://www. uniprot. org/). Venn diagrams were constructed to summarize the number of candidate genes identified using the VennDiagram R package  [51]. In addition, the sequences of the candidate genes were categorized functionally by Gene Ontology (GO) terms  [52] , disregarding those with hypothetical function. The terms were obtained using the Blast2GO software with the default parameters specified by the program  [53]  and were previously simplified using the GO Slim feature.
brasilense and 22 to N stress. Regarding the models, 13 significant associations were identified by using the additive GWAS model and 34 the heterozygous (dis). Finally, the nature of the SNP effect on the traits, positive or negative, was independent of the treatment or GWAS model (S6, S7, and S8 Figs). The categorization of candidate genes sequences according to biological process using the Blast2GO software showed that just one biosynthetic category was present in all treatments (Fig 3B ). Moreover, in general, the candidate genes found by additive GWAS model tended to be mainly enriched for terms such as "DNA metabolic process" and "lipid metabolic process". In turn, those found by the heterozygous (dis)advantage model showed more exclusive biological functions; for example, "catabolic process", "cellular component organization", "response to stress", and "secondary metabolic process".
Sample Size There were no data available regarding the expected difference between the three Test products and Control nor data regarding the expected residual error variance associated with the primary characteristic to be studied (i. e. , total sum blood eAA incremental Area Under the Curve (iAUC) over 4 hours). As a consequence, the adequacy of the trial size was assessed using a range of plausible Coefficient of Variations (CV) from 15% to 35%, by steps of 5%. Using these values, the power of the trial to show equivalence for a pair of products in a 4 × 4 Williams crossover design given a sample size of 16, a desired type I error at alpha (α) level of 0. 1, and two-sided with 5000 simulations keeping CVs of 15% to 20%, resulted in a power of 86-98%. We anticipated a screening failure rate of 50% and a drop-out rate of 20%; therefore, approximately 40 subjects were planned to be screened.
Despite equal leucine, WPI resulted in significantly greater blood leucine concentrations compared to wheat protein hydrolysate. However, wheat protein hydrolysate did increase myofibrillar protein synthesis rates above basal rates  [7]. In the present study, we were able to provide less absolute protein than these previous studies, while matching leucine levels. Although our study did not directly measure MPS, as a surrogate measure and secondary endpoint, we measured the blood leucine kinetic response (C max and T max ). Like previous studies, the leucine concentration in the blood from our plant-based interventions was not bio-equivalent to WPI. However, an interesting finding was that the leucine T max of Blend #1 and Blend #3 were similar to WPI. Additionally, data across the plant-based protein blends showed an approximate two-fold increase in leucine concentration from fasting levels.
From a physiological standpoint, the leucine data provide evidence of a rapid hyperleucinemia, which is a critical response associated with postprandial MPS  [1]. Future studies are required to assess the ability of high-quality plant-based protein blends to stimulate MPS. PDCAAS is the mathematical product of the true fecal nitrogen digestibility coefficient and the eAA amino-acid profile of the protein sources  [15]. We initially calculated PDCAAS scores of the plant-based protein blends to that of WPI, a value of 1. 0. Given that plant proteins are deficient in one or more of the essential amino acids when compared to animal proteins, we compensated in our formulas by adding more grams of protein to the plant-based blends to increase the leucine content to match WPI  [15]. Naturally occurring dietary antinutritional factors found in plant-based proteins (such as phytates, tannins, and trypsin inhibitors) have been shown to negatively impact the digestibility and bioavailability of consumed dietary protein derived amino acids  [16].
Systematic literature review We conducted a systematic literature review (SLR) of comparative efficacy and safety of antivirals for the treatment of influenza in accordance with the methods developed by the Centre for Reviews and Dissemination (CRD)  11   Abstracts from conferences and congresses were also searched in several relevant websites. Further sources, such as ClinicalTrials. gov and regulatory websites (EMA, FDA and PMDA) were consulted in order to capture relevant documents; details of conferences, congresses, additional sources and the selection process as well as the search strategies implemented can be found in the Supplementary Appendix. No restrictions in terms of timeframe or geographical scope were applied. Searches for conference/congress abstracts were restricted to 2015 or more recent.
including a low proportion of patients outside this age range or with some risks factors) were included in the NMA. Detailed criteria for inclusion and exclusion of studies are provided in Table  1. The analysis was conducted in the intention-to-treatinfected (ITTI) population for efficacy outcomes (i. e. patients with confirmation of influenza infection based on laboratory tests) and the total trial population for safety outcomes (i. e. patients with and without confirmation of influenza infection). In a sensitivity analysis, we restricted the analysis   influenza health status, incidence of pneumonia and drugrelated diarrhea are provided in the Supplementary Appendix. The NMA models were estimated in a Bayesian framework using a Markov Chain Monte Carlo (MCMC) method as implemented in the WinBUGS software package.
In the study by Turner et al. 46  , the results for efficacy outcomes were in favor of active treatments versus placebo (sometimes statistically significant) and no significant differences were found in terms of safety outcomes between active treatments and placebo. These results are in line with our findings. The strength of this NMA was that it was based on an SLR searching for several databases including Japanese ones with extensive hand searches. The number of included trials was quite high compared to the number of treatments considered in the analysis  6  , ensuring data availability for most relevant outcomes, and that results for each treatment were not dependent on a single trial. Also there was no major impact on the results in the sensitivity analysis with more strict inclusion criteria, suggesting that the analysis was robust regarding the selection of studies.
Acknowledgements Creativ-Ceutical Ltd performed the NMA, funded by  Shionogi & Co. Ltd. The authors wish to thank  Takahiro Hasegawa  ( Shionogi ) for biostatistics analysis support and  Yutaka Saisho  ( Shionogi ) for medical input. We also thank  Yoshie Onishi  ( Creativ-Ceutical ) for collaboration and valuable technical input, and  Nawel Jaafer  and  Monique Dabbous  ( Creativ-Ceutical ) for medical writing support.
, 2010 24 NCT00799760 CI 18-85 Zanamivir 10 mg Oseltamivir 75 mg Watanabe et al. , 2010 25 NCT00803595 CI 20-77 BID þ placebo Laninamivir 40 mg BID þ placebo Oseltamivir 75 mg BID Boivin et al. , 2000 26 Makela et al. , 2000 27 NR NR ILI ILI >12 12-81 Zanamivir 10 mg BID Zanamivir 10 mg BID Placebo Placebo Monto et al. , 1999 28 Hayden et al. , 1997 29 Campion et al. , 1998 30 NCT00419263, 2007 31 Ikematsu, 2011 32 Kashiwagi et al. , 2000 33 NR NR NR NCT00419263 NR NR ILI ILI ILI CI CI ILI >13 >13 >12 >18 children þ adults 16-80 Zanamivir 10 mg BID Zanamivir 10 mg BID Zanamivir 10 mg BID Peramivir 300 mg Laninamivir 40 mg Oseltamivir 75 mg BID Placebo Placebo Placebo Placebo Zanamivir 10 mg BID Placebo PMDA zanamivir package insert 34 NR CI Adults Zanamivir 20 mg Placebo PMDA laninamivir report 35 NR NR Adults Laninamivir 40 mg Oseltamivir 150 mg Placebo FDA oseltamivir 36 NR CI >13 Oseltamivir 150 mg Placebo Abbreviations.
Different data were collected by compiling information available on the website of 76 Oasis projects across France: people living in the community; lodging possibilities; availability of a school; and direct relationship with local farmers. Then, a social factorial correspondence analysis and an environmental factorial correspondence analysis were realized to evaluate the impacts of environmental Oasis projects. The results show that profitable organizations seem to conduct more social and environmental activities in an agro-ecology context, and they put in place more actions than those who have no profitable aims.
MATERIALS AND METHODS To better understand the environmental and social actions of both nonprofit and for-profit organizations, the 76 Oasis projects across France were analyzed. The data were collected by compiling information available on their websites. Oasis projects are part of the Hummingbird movement, created by Pierre Rabhi in line with his "decentered and eco-centric humanism"  (Moser, 2016)  Established in 2007, the Hummingbird movement is multifaceted. It aims to support a healthy and sustainable community to foster dynamic transition that benefits everyone. The movement promotes assistance through a web page 2 where project directors describe their needs (in terms of volunteers, equipment loans, etc. ). The Hummingbird movement also offers training via a magazine and MOOCs on food and farming, buildings and energy, and health.
In addition, there is Hummingbird Agora, a participatory think tank, where members can contribute and reflect. Finally, the movement organizes events (such as choral activities), produces films, edits books, and provides open source tools. The authors chose to study the Oasis project organizations, which aim to produce local food, because their focus on agro-ecology promotes a method of production that integrates agricultural activity with the environment. To capture the social and environmental aspects of a sustainable strategy, various actions were selected. The data were collected by compiling information available of their website. Social interaction with others is approximated by: 2 https://colibris-lafabrique. org/liste-des-projets 1) number of people living in the community; 2) number of lodging possibilities; 3) presence of a school, to share knowledge with the youngest; and 4) direct relationship with local farmers.
ANALYSIS AND RESULTS To control the different steps of the analysis, environmental and social factorial correspondence analyses were independently performed. As underlined by  Hoffman and Franke (1986) , a factorial correspondence analysis aims to collect most of the initial qualitative information in a reduced number by focusing on the correspondences between variables; it scales the rows and columns of a data matrix in corresponding units displayed graphically in the same space. In these two factorial correspondence analyses of the Oasis projects, each organization was given a grade (A, B, or C) reflecting their environmental and social actions. Grades were awarded depending on the number of actions supporting the natural environment: grade C from 0 to 4; grade B from 5 to 7; grade A from 8 to 11.
However, it is possible to identify two main limitations to this investigation on the environmental Oasis projects: • The first limitation is due to the data collection methodology. The data collected are general, and do not provide in-depth details on environmental actions. For example, if a website indicates that renewable energy is used in a project, the reader ignores the proportion of renewable energy consumption in relation to the total energy consumption of this project. Thus, the absence of direct contacts and exchanges with decision makers prevents to put the results obtained into perspective. • The second limitation is linked to the lack of sensitivity analysis in the grade construction (e. g. , the impact of the variability of the model's input factors on the output variable). Sensitivity analysis would make it possible to understand the weighted and differentiated effects of the different environmental actions, for example, the ecological wastewater treatment or the production of seeds, on the environment according to different dimensions of the triple R approach.
Prevalence and Diversity of ICEs and IMEs in S. suis Strains Belonging to Various Serotypes Analysis of 214 genomes of S. suis strains belonging to 27 different serotypes revealed 232 ICEs with a full sequence, 49 ICEs with a partial sequence (due to sequencings gap(s) in the de novo assembled genome) and 135 elements deriving from ICEs (with truncated recombination and/or conjugation genes, called dICEs). IME-related elements appeared more prevalent than ICEs since 406 IMEs and 51 elements deriving from IMEs (with truncated integrase or relaxase gene, called dIMEs) were detected. Most of the ICE-related elements found in S. suis genomes encoded a canonical relaxase of the MOB P family (n = 402) associated with a coupling protein of the VirD4 family. By contrast, more diversity was observed for IMEs with canonical relaxases of the MOB C , MOB V or MOB Q families or putative non-canonical relaxases with various domains found in RCR initiators (PF02486 or MOB T , PF01719 associated or not with a helicase domain, PF02407, PHA00330 or MOB T + MOB V ).
These relaxases were associated or not with a coupling protein (of the TcpA family except for those harboring a MOB C relaxase that is associated with a VirD4 CP) (Figure  1  and Table  S1 ). Only one strain devoid of ICE and IME was identified. This strain did not possess any acquired resistance gene (Table  S1 ). Pathogens 2020, 9, x FOR PEER REVIEW 3 of 23 Elements were grouped according to the nature of their relaxase and the presence or absence of an associated coupling protein. * TnGBS1 is indicated in the elements with a MobP relaxase but it should be pointed out that its relaxase is only distantly related to MobP relaxases and does not possess the characteristic PF03432 domain of this family  [23]. The sizes of the circles are at scale, except when zooming to provide further details.
The integration sites of the IMEs are indicated in the element names themselves. Elements were grouped according to the nature of their relaxase and the presence or absence of an associated coupling protein. * TnGBS1 is indicated in the elements with a MobP relaxase but it should be pointed out that its relaxase is only distantly related to MobP relaxases and does not possess the characteristic PF03432 domain of this family  [23]. The sizes of the circles are at scale, except when zooming to provide further details. The integration sites of the IMEs are indicated in the element names themselves.
Inner circles indicate IMEs with a low specificity of integration (in light grey on the 11th circle), in ebfC gene (in dark brown on the 12th circle) and in guaA (in black on the 13th last inner circle). One element resulting from recombination between an IME_SNF2 and an IME_PPI (called "hybrid" in Table  S1 ) is indicated by a star. When several elements are present at the same integration site, the number of elements is indicated in the box (for example, 3 IME_tRNALeu in strain NSUI237). It is difficult to define families for IMEs since a relaxase of a given family (defined according to phylogenetic analysis and 40% sequence identity clustering  [22] ) can be associated with different families of coupling proteins (for example, relaxase with a PF02486_6 domain can be associated with two different CPs in S.
suis IMEs, Figure  S1 ). In the same way, a coupling protein of a given family (for example, a TcpA_12 coupling protein) can be associated with different families of relaxases (2 different relaxases for the example of TcpA_12, Figure  S1 ). In total, twenty-two different combinations of integrase-relaxase-(coupling protein) were observed for IMEs (Figure  S1 ). The highest diversity was observed for IMEs integrated into rpsI and into a tRNALeu gene (Table  S1 , Figure  6 ). It is difficult to define families for IMEs since a relaxase of a given family (defined according to phylogenetic analysis and 40% sequence identity clustering  [22] ) can be associated with different families of coupling proteins (for example, relaxase with a PF02486_6 domain can be associated with two different CPs in S.
ICEs carrying AMR Genes in S. suis A total of 55 AMR genes were found on ICEs (excluding ICEs hosting IMEs carrying AMR genes). Most of the ICEs carrying AMR genes belong to the Tn5252 family (see Figure  7  for representative ICEs of this family). AMR genes were also found on four other ICE families (Figure  8 ). The first one is the vanG family with elements integrated into a lysS gene (with a tet(W) gene). The second one is the TnGBS2 family (one ICE with tet(L)-ant(6)-Ia-aph(3 )-IIIa genes). Interestingly, a thorough analysis of the TnGBS2-related ICE indicated that the cluster of AMR genes could have been brought by the integration of an IME inside the ICE. Indeed, a gene encoding a serine recombinase was detected as well as a gene encoding a relaxase with a PF01076 domain (Mob V family).
PCR experiments-by both PCR and nested PCR-did not show excision of the erm(B) element (data not shown). Many defective elements related to IME_NSUI084_SNF2 and IME_SsuNSUI086_PPI or signatures of the integration of these IMEs-truncated SNF2 or PPI genes-were detected in the genomes (Figure  7  and Table  S1 ). Conjugation experiments were carried out in order to evaluate the conjugative transfer of Tn5252-related ICEs from strains NSUI084 and NSUI086 (ICE_SsuNSUI084_rplL and ICE_SsuNSUI086_rplL respectively). Whatever the donor, no transconjugant was obtained using S. suis NSUI029 strain as a recipient (frequency below the detection limit of 10 -7 per donor cells). By contrast, a conjugative transfer of ICE_SsuNSUI084_rplL_2-the Tn5252-related ICE part of the composite element-was obtained using S.
thermophilus LMG18311 (pMG36e) as a recipient (at a high frequency of 2 × 10 -3 ± 1. 10 -3 per donor cells). This ICE was still able to excise from the rplL site in the transconjugants (Figure  10 ), but as in the initial donor strain, IME_NSUI084_SNF2 hosted by the ICE was still unable to excise (data not shown). One of these transconjugants was used as a donor in mating experiments after plasmid curing with S. thermophilus LMG18311 (pMG36e) as a recipient. Transconjugants were obtained indicating that the ICE is able to retransfer (with a similar frequency) (Figure  S2 ). Pathogens 2020, 9, x FOR PEER REVIEW 14 of 23 Conjugation experiments were carried out in order to evaluate the conjugative transfer of Tn5252-related ICEs from strains NSUI084 and NSUI086 (ICE_SsuNSUI084_rplL and ICE_SsuNSUI086_rplL respectively).
This further extends the repertoire of IMEs found in Streptococci  [23]. Twenty-two different combinations of integrase-relaxase-(coupling protein) were observed. This indicates a high dynamics of evolution and plasticity of IMEs as suggested previously  [22]. As for ICEs, tandem accretion of IMEs also exists, enabling gene exchange and increasing the evolution potential of these elements. As observed in a previous study on complete genomes of streptococci  [22] , we did not find IMEs carrying canonical relaxases of the Mob F or Mob H families but the four other canonical families (MOB P , MOB Q , MOB V, and MOB C ) were detected. More importantly, half of the IMEs harbor a putative non-canonical relaxase, i. e. , related to RCR initiators (MOB T , PF01719, PF01719-helicase, PHA00330 or PF02407) and in most cases these IMEs also encode a coupling protein (always from the TcpA family).
Nucleotide Sequence Accession Numbers Bacterial genomes analyzed in this work were sequenced previously  [11, 40, 45]. DNA sequencing short-reads (see accession numbers listed in Table  S1 ) were retrieved from the Sequence Read Archive of NCBI (https://www. ncbi. nlm. nih. gov/sra). De novo assemblies were carried out with the A5 pipeline  [46]. Contigs were annotated with Prokka (v. 1. 12,  [47] ).
Search for ICEs, IMEs and for Resistance Genes in Streptococcal Genomes The overall workflow of the strategy used to detect, characterize, and delineate ICEs and IMEs in streptococcal genomes was described previously  [10, 22]. Resistance genes were searched using MegaBlast (using default NCBI parameters and no filtering) against the ARG-annot database  [48]  (as uploaded on 2017/06/25). The localization of the resistance genes on chromosomal genetic elements (ICEs, IMEs, prophages or other genomic elements) was thoroughly examined by visual inspection of surrounding genes in the genome and analysis of their putative function by CD-search on NCBI website.
RAD-seq library construction and sequencing. A total of four RAD-seq libraries from the two parents and their 152 offsprings were constructed and sequenced. Approximately 6. 55 Gb (BT) and 7. 24 Gb (OB) raw data were generated prior to any quality filtering for the parents, while 6. 52 Gb (BT; 21. 73 million reads) and 7. 22 Gb (OB; 24. 09 million reads) were kept after quality filtering (Supplemental Table  S1 ). About 95. 6% (minimum 93. 38%) of reads had an average quality higher than Q20 (Q20 indicates a 1% chance of error), indicating the high-quality of the data. For the 152 individuals, sequencing of the RAD libraries generated a total of 193. 12 Gb raw data. Of the raw reads, an average of 3. 55 million reads per individual were retained after removing the putatively duplicated reads and reads without intact EcoRI cutting sites (average complete enzyme digestion ratio was 94.