dataesr/scientific-paragraphs-categorization huggingface dataset:
Animals The dogs in the cohort studied were all referred to the Royal Canin Weight Management Clinic, University of Liverpool UK, for investigation and management of obesity. Eligible cases were: originally seen between November 2004 and July 2012, started a weight management program, and reached a known end-point for their weight loss (i. e. , completed, stopped prematurely, or died [see below]) by February 2013. Additional eligibility criteria included having data available from the preliminary investigations undertaken before weight loss (see below), and having had body composition analysis conducted by dual-energy X-ray absorptiometry (DEXA). 23 Given the study timeframe and broad eligibility criteria, dogs used in previous studies assessing weight loss in selected cases that successfully lost weight only,  13, 14  and also in a study examining subsequent rebound after successful weight loss.
Weight Loss Regimen Complete details regarding the weight loss protocol used at the clinic have been described. 13, 14 Briefly, dogs were determined to be systemically well, and without abnormalities that would make controlled weight loss inappropriate by complete blood count, serum biochemical analysis and urinalysis. Serum free thyroxine concentration was measured by equilibrium dialysis at an accredited external laboratory a to determine thyroid status. Throughout weight loss, dogs were weighed on electronic scales, b which were regularly calibrated using certified test weights. c Body composition was analyzed before and after the weight loss regime in all dogs, using fan-beam DEXA. d Body composition results from before weight loss were used to estimate ideal weight. 10, 19 Briefly, the body composition data were entered into a computer spreadsheet, e containing a purpose-created mathematical formula to predict expected body composition after weight loss at different weights.
Statistical Analysis All data are expressed as median (range), except where indicated, and there were no missing data. Statistical analyses were performed with computer software, j with the level of significance set at P <. 05 for two-sided analyses. Given that this was an observational cohort study, and no such study had previously been conducted, a sample size calculation was not performed. Instead, the principle determinant of sample size was the number of dogs seen that met the eligibility criteria during the study timeframe. The Shapiro-Wilk test was used to determine whether or not datasets were normally distributed, and either parametric or nonparametric tests were then performed as appropriate. For continuous variables, differences among groups were assessed with the Kruskal-Wallis test, with post hoc comparisons made, where appropriate, using the Dwass-Steel-Critchlow-Fligner test.
lentiflavum isolates were identified on the basis of 99. 6 % ± 0. 003 % similarity with the reference M. lentiflavum CIP 105465 T partial rpoB sequence [GenBank:EU109300]. The six M. lentiflavum patients were co-infected by Staphylococcus aureus, Gramnegative bacilli and fungi and were all under azithromycin long-term low-dose prophylaxis (250 mg three times a week). In two patients, M. avium had been previously isolated in 2004 and 2012 from respiratory tract specimens (Table  2 ). The female/male sex ratio of M. lentiflavum patients (0/6) significantly differed from that of the NTM positive cohort (199/155; 56. 2 %) (p = 0. 007, Fisher exact test) and from that of patients with another NTM (11/9; 55 %)  (p = 0. 02). It further differed from that of M. avium complex patients (5/3; 63 %) (p = 0.
lentiflavum shares <96 % similarity regarding the rpoB gene sequence with closely related species, including Mycobacterium stomatepiae DSM 45059, Mycobacterium florentinum DSM 44852, Mycobacterium genavense FI-06288 and Mycobacterium triplex ATCC 700071 [GenBank:HM022213, HM022205, HM022216 and GQ153311]. Moreover, the routinely used 16S-23S rRNA intergenic spacer sequencing  [5] , hsp65 restriction fragment length polymorphism and sequencing  [13] , and commercial probes for M. avium complex  [7, 8, 13]  may not be sufficiently discriminative as, for example, M. lentiflavum shares > 99 % similarity in the 16S rRNA gene sequence with M. simiae  [1]. M. lentiflavum has emerged over a five-year period as the third most prevalent NTM isolated from the respiratory tract in our cystic fibrosis cohort.
Selection of experts and data collection In each of the collaborating countries (Belgium, France, Germany, Sweden, Denmark and Switzerland) the responsible consortium partner identified pig production experts in their respective countries based on common knowledge or personal and institutional experience and invited them to participate in the written survey between July 2012 and February 2013. In Belgium 44 experts were contacted, in Denmark 290, in Germany 18, in France 20, in Sweden 49 and in Switzerland 30. In Belgium, Germany, France, Sweden and Switzerland a personal approach was used to invite the experts to participate in this study. In Denmark the invitations for participation were send out by mail through the Danish Agriculture and Food Council all pig experts in their database. People with a known expertise in porcine medicine and/or antimicrobial usage and their alternatives were considered to have sufficient knowledge to oversee the complexity of alternatives to antimicrobial usage in pig production and therefore selected as experts: veterinary practitioners, scientists active in pig herd medicine (professors/teachers, researchers), nutritionists, technical consultants from the pharmaceutical industry and veterinary consultants/advisors active in the pig industry.
Data analysis -Categorical Principal Components Analysis Results were analyzed using descriptive statistics in IBM SPSS Statistics version 22 and data management was done using Microsoft Excel. Comparisons between countries and professions per alternative and parameter was conducted using an univariate general linear model with Scheffé test for post hoc group comparisons. If equality of variance could not be assumed, an appropriate transformation of the data was performed. The Categorical Principal Component Analysis (CATPCA) was used to graphically visualize the relatedness between the perceived effectiveness, feasibility and ROI of the different alternatives. The CATPCA was favourite above a standard PCA for the fact that it the alternatives were scored as ordinal variables  (Linting and van der Kooij, 2011).
The CATPCA returns the data as a two dimensional graphical presentation where categorical variables were transformed in an optimal scaling process into metric variables. The variance accounted for represents the squared distance of the vector tip to the origin. To adjust for the fact that zero was amongst the possible answers, the SPSS procedure of discretizing the variables by means of multiplying was used. Variables were given an ordinal measurement scale, while the two supplementary variables "country" and "profession" were set as "not specified". The number of dimensions was limited to 2, allowing for the two dimensional graphical visualization. Missing values were handled by using the standard CATPCA method of imputing the modal category. Variable principal normalization was used as an option to optimize the associations between variables.
Funding This project was part of the European MINAPIG project (Evaluation of alternative strategies for raising pigs with minimal antimicrobial usage: Opportunities and constraints, http://www. minapig. eu), which was funded by the ERA-NET programme EMIDA (EMIDA19) 5 and by the participating national funding agencies. Since the Belgian partner (Ghent University) was not eligible to receive any funding through the EMIDA ERA-net funding scheme, Boehringer Ingelheim provides limited financial support (12. 500D/year) to cover some of the travel and field study expenses needed to fulfil all tasks within the MINAPIG project. There are no other companies that provide financial support. Boehringer Ingelheim is a formal partner of the EMIDA ERA-NET consortium. Industry participation is encouraged in this programme.
europaeum CSUR P1344 isolate (3) in order to increase knowledge and gain insights into this organism, which is potentially involved in the contamination and/or infection of airways. Genomic DNA was isolated from M. europaeum strain CSUR P1344 and grown onto Middlebrook 7H10 solid medium (Becton, Dickinson, Le Pont-de-Claix, France) at 37°C in an atmosphere enriched with 5% CO 2. It was sequenced by parallel paired-end and mate pair high-throughput MiSeq technology (Illumina Inc, San Diego, CA, USA). Starting from 1. 5 g genomic (gDNA) fragmented with an optimal size at 6 kb, the mate pair Nextera library was constructed with an input of 1 ng of gDNA. Both libraries were sequenced on MiSeq in 2 ϫ 251 bp, and final sequencing produced a total of 1,047,703 reads. The whole set of reads was trimmed using Trimmomatic (5) and then assembled through the assembler software Spades (6, 7).
Contigs were combined together by SSPACE (8), Opera  (9)  helped by GapFiller  (10) , and homemade tools in Python to refine the set. Finally, the draft genome of M. europaeum CSUR P1344 consists of 13 contigs without gaps, containing 6,152,523 bp. The GϩC content of this genome is 68. 18%. Noncoding genes and miscellaneous features were predicted using RNAmmer  (11) , ARAGORN  (12) , Rfam  (13) , Pfam  (14) , and Infernal  (15). Coding DNA sequences (CDSs) were predicted using Prodigal  (16) , and functional annotation was achieved using BLASTϩ  (17)  and HMMER3  (18)  against the UniProtKB data-base  (19). The genome was shown to encode at least 74 predicted RNAs, including 3 rRNAs, 50 tRNAs, 1 tmRNA, and 20 miscellaneous RNAs. A total of 5,814 identified genes yielded a coding capacity of 5,560,314 bp (coding percentage: 90.
37%). Among these genes, 295 (5. 07%) were found to be putative proteins and 1,061 (18. 25%) were assigned as hypothetical proteins. Moreover, 4,005 genes matched at least one sequence in the Clusters of Orthologous Groups (COGs) database  (20, 21)  with BLASTp default parameters. Nucleotide sequence accession numbers. The M. europaeum CSUR P1344 strain genome sequence has been deposited with its annotations at EMBL under the accession numbers CTEC01000001 to CTEC01000013.
Therefore, we propose a shift from a static toxicity assessment to a dynamic one. In the present study, we monitored cell viability of HepaRG cells using impedance metrics. We propose here both the generation of long-and short-term data by exposing HepaRG cells to three hepatotoxic cosmetic related compounds, coumarin, isoeugenol and benzophenone-2 for 48 h (single exposure) and 4 weeks (repeated exposure) and the analysis of these data using a mechanistic model based on systems of ordinary differential equations which account for the time course of the effect. We also address the issue of extrapolating from acute to chronic exposure by assessing the ability of models calibrated using acute data to predict chronic data. If short term testing could enable the reliable prediction of long-term in vitro toxicity, this would result in savings both in terms of time and money.
(  3 )), and (ii) a decrease in compound concentration due to cell metabolism (Eq. (  4 )). dc i dt ¼ Àk Â c i (3) dc i dt ¼ À V max;estim Â c i K m þ c i Â N N 0 (4) where k is the unspecific decrease constant, V max,estim the maximum metabolism rate of HepaRG cell, estimated with the impedance data, K m the Michaelis Menten constant, N the number of cell at time point and N 0 the number of cells at reference time. K m was obtained from unpublished metabolism experiments on human primary hepatocytes performed at INRA Toxalim (Sophia Antipolis, France). The metabolism data are summarized in Table  1. We assumed that the K m values are roughly similar between human primary hepatocytes and HepaRG cells and that the differences between the two would be chiefly attributable to metabolic rate. To analyze cell population viability dynamics, we propose the following model, which correlated effects to intra-cellular concentration and accounts for the fact that no cell population growth is expected for HepaRG, as proposed by  Pery et al.
Coumarin Isoeugenol Benzophenone-2 V max (nmol/min/10 5 cells) 6. 50 Â 10 À3 0. 295 0. 324 K m (mM) 1. 6 7. 9 34. 19  observed an increase of the NCI for roughly 10 h after the following medium renewal. Since it was a reversible increase during less than 1 h, it was considered as an artefact which did not affect the cytotoxicity. This may also be due to the shortage of certain medium compounds during the medium renewal. The values in these intervals were removed from the dataset and from the data analysis. [ ( F i g. _ 1 ) T D $ F I G ] We estimated the parameters' values together with their confidence intervals using the least squares method. Genoud's algorithm of Rgenoud package  (Mebane and Sekhon, 2011)  implemented in R software (R Development Core Team, 2013) was used for the model adjustment.
95% confidence intervals were calculated through bootstrapping with 1000 re-sampled datasets. Sampled datasets were built by sampling variations of NCIs between two time points in each of the replicates. Once the BK/TD model had been calibrated for each compound after long-and short-term exposure, we checked the ability of the acute BK/TD model to predict long-term exposure and, inversely, the ability of the chronic BK/TD model to predict short-term exposure.
It was not possible to identify the most accurate models solely on the basis of the GOF of the impedance data (Table  2 ). Therefore, complementary experimental data are required, particularly in relation to metabolism. Fortunately, such information was available from other experiments (unpublished at the moment) performed at INRA Toxalim. Human primary hepatocytes were exposed to the three compounds we studied here in order to measure metabolism. Coumarin's maximum velocity (V max ) on human hepatocytes was 0. 0065 nmol/min/10 5 Parameters estimated with the chronic BK/TD models, with k being the elimination rate of the compound due to unspecific mechanisms, k met the metabolism rate, NEC the estimated no effect concentration (threshold below which there is no effect on cell viability), b the killing rate by the compound.
Thus, within this project, datasets have been generated in order to investigate long term repeated dose toxicity in three targeted organs (i. e. , the liver, the kidney and the central nervous system), and a mechanism-based model of cellular toxicity has been developed for renal epithelial cells (RPTEC/TERT1) exposed repeatedly for 14 days to the nephrotoxin cyclosporine A  (Wilmes et al. , 2013). In the present study, we proposed an approach providing long-term, real-time toxicological data using impedance metrics and also a methodology for analyzing these data. Due to the cost of long-term toxicity testing, we also addressed the issue of using acute toxicity data to extrapolate to chronic toxicity data. Through our study, we showed that acute-to-chronic extrapolation might lead to inaccurate predictions of chronic toxicity.
Acknowledgments This work was supported by the  European Community 's  Seventh Framework Program (FP7/2007-2013) and by  Cosmetics Europe  through the  COSMOS  project (grants agreement no. 266835 ). The authors thank  Frederic Bois ,  Cleo Tebby  and  Enrico Mombelli  for their thorough review of this article. The authors thank  Morningside Translation Inc. , for the review of this article. The authors thank the reviewers for their thorough review of this article which greatly helped to improve both the content and the clarity of the manuscript.
Performance data All annual results for trotters that took part in French races from 1996 to 2011 were provided by the Society for the Promotion of French Horse Breeding (SECF, Société d'encouragement à l'Elevage du Cheval Français), the parent corporation for trotting races in France. The following data were available for each horse for each year for both harness racing and racing under saddle: annual earnings, number of races entered and number of times a horse was disqualified. An additional dataset containing qualification dates for all qualified horses and the best-recorded time per kilometer was provided by the French Institute for Horses and Riding (IFCE, Institut Français du Cheval et de l'Equitation). Pedigrees were also provided by the IFCE. Considering that a horse can race from 2 to 10 years of age, data on complete careers were only available for horses born between 1994 and 2001.
Data were truncated for horses born between 1986 and 1993, for which data on early performances were missing, and for horses born between 2002 and 2009, for which data on late performances were missing. In order to take selection on performance at 2, 3 and 4 years of age into account, only horses born after 1994 were considered. Horses born after 2008 were also excluded because of the lack of data on performance at 3 years of age. In summary, all performances of horses born between 1994 and 2008 were included in the study, although the performances of some of the horses born between 2001 and 2008 were truncated. However, this was accounted for by introducing a birth year effect in the analysis model. Thus, the dataset consisted of 173 176 born French trotters, 64 274 qualified trotters (37.
Horses Blood samples used in this study were collected previously for a GWAS study on osteochondrosis in French trotters  [5]. Animals included in the osteochondrosis study were recruited at CIRALE, the French Imaging and Research Center on Equine Locomotor Disorders, and at a few veterinary clinics from 2008 to 2010. The data comprised 682 genotyped horses. For the current study, 630 horses were retained based on birth year because performances were only available for horses born between 1996 and 2008. Among the 630 horses included in our analysis, 496 (79%) were qualified, which is a much higher proportion than in the overall French trotter population during this time period (37%) and average earnings per finished race were approximately three-quarters of a phenotypic standard deviation higher than the average of the overall French trotter population.
Methods to estimate effects of the DMRT3 gene First, traits were studied by classical quantitative genetic analysis using all available performance data to determine fixed environmental effects and estimate heritabilities and genetic correlations. Then, the performances corrected for fixed effects were used in a mixed linear model on the genotyped sample in order to determine the effect of the genotype at SNP BIEC2-620109, taking into account the polygenic effect. This model, called FASTA and proposed by  [6] , was best suited to our situation to reduce type I errors without loss of power  [7]. The model used to analyze the performances of the entire dataset was: y ¼ Xb þ Za þ Zp þ e ð1Þ For continuous traits, y is the vector of performances while for traits with binary variables (qualification and disqualification), y is the vector of performances that underlie the trait, since a threshold model was used  [8].
For a repeated performance, pj is the mean of estimated permanent environmental values for the horses of cohort j. The adjusted performance is ỹij j1 ¼ Eðy ij j1Þ-bj : for a nondisqualified race, and ỹij j0 ¼ Eðy ij j0Þ-bj for a disqualified race. The phenotypic variance used in model (  2 ) was that of model (1), although using expected values alters the variance of adjusted performances. Heritabilities and both genetic and residual correlations were those estimated in model  (1). For repeated performances, the residual correlation was that of the permanent environmental effects. E y ij j1 ¼ bj þ âj þ pj þ σ y φ s-b j þ âj þ pj ð Þ σy 1-Φ s-b j þ âj j þ p j i σy 0 @ 1 A 2 E y ij j0 ¼ bj þ âj þ pj þ σ y φ s-b j þ â j þ p j ð Þ σy Φ s-b j þ â j j þ p j i σy 0 @ 1 A 2 In order to estimate the effect of the genotype at SNP BIEC2-620109, performances were analyzed using a multi-trait model (see explanations for the variancecovariance matrices above) with the same groups of traits as those used to calculate the genetic parameters for the entire dataset (listed above), and the same variance-covariance matrices for genetic values and residuals.
ASREML software was used  [10]. GWAS was also performed for all traits with the remaining 41 710 SNPs, and because of the amount of time required for such a large number of analyses, single-trait models were used. QQ plot analysis was performed to check the distribution of the test statistics. The type I error threshold to detect potential quantitative trait loci (QTL) was set to 5. 10 -5 , as in  [5]  for the same sample (The Wellcome Trust Case Control Consortium, 2007,  [11] ).
The system was operated at a flow rate of 300 nl min Ϫ1 , and a 120-min gradient was used to separate the peptides. The mass spectrometer was operated in the Top 10 data-dependent acquisition mode. Precursor scans were performed in the Orbitrap column at a resolving power of 70,000, from which the 10 most intense precursor ions were selected by the quadrupole and fragmented by higher-energy collisional dissociation (HCD) at a normalized collision energy of 28%. The quadrupole isolation window was set at 3 m/z. Charge state ϩ1 ions and undetermined charge state ions were rejected from selection for fragmentation. Dynamic exclusion was enabled for 40 s. Data were converted from RAW to MGF files using the ProteoWizard program  (36). Mass spectrometry data analysis. Data were searched against the L.
interrogans serovar Copenhageni strain Fiocruz L1-130 proteome using the Andromeda algorithm  (37)  through MaxQuant software (version 1. 5. 2. 8)  (38). Parameters can be found in Table  S3  in the supplemental material. Contaminants, reverse decoy proteins, and proteins identified only by a modification site were removed; majority protein identifiers were used as protein identifiers. Raw protein abundances were used for further analysis. Missing values were replaced with the minimum for each sample. The resulting protein intensities were log 2 transformed and quantile normalized  (39) , using the method implemented in the normalize-BetweenArrays function of the limma package  (40, 41). An empirical Bayes moderated t statistic, as implemented in the R limma package  (40) , was applied to identify proteins with a significant difference in abundance.
Exoproteins with potential moonlighting functions. Moonlighting proteins are a class of proteins in which a single polypeptide chain performs more than one biochemical function  (49). Classification of exoproteins into COGs revealed the overrepresentation of proteins involved in nutrient uptake and metabolism, with the latter comprising numerous proteins involved in the glycolytic pathway (Fig. 2 ; see also Table  S2  in the supplemental material). Enzymes in the glycolytic pathway have been implicated as having moonlighting properties in other bacteria  (50) (51) (52) (53)  and in Leptospira  (23). To assess potential moonlighting properties for Leptospira exoproteins, proteins that have been experimentally characterized to display moonlighting properties in other microorganisms were collected from the MoonProt database  (49).
The primary sequences of these proteins were then used in basic local alignment searches against the L. interrogans proteome. The search results were compared with the proteomic data in Tables S1 and S2 in the supplemental material to identify orthologous proteins in the proteomic data. This approach identified in the supernatant 32 proteins that could be classified as moonlighting proteins (Table  4 ). A total of 45 proteins orthologous to moonlighting proteins were identified in L. interrogans; 15 of these were exoproteins, and 17 others were detected in supernatants (to be deemed exoproteins, proteins had to display a statistically significantly higher abundance in supernatants). Exoproteins are immunogenic and not essential for Leptospira virulence. To begin to characterize exoproteins in the context of pathogenesis, WCPs and CSPs were used in immunoblot experiments with L.