dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical Analyses Statistical analyses were carried out using SPSS software, version 20. 0 (SPSS, Inc. , Chicago, IL, USA). Demographic characteristics (age, gender) anthropometric characteristics (height and weight), clinical (systolic and diastolic blood pressure) and biochemical measurements (lipid profile, glucose, VitD) were compared according to H. pylori infection using chi-square tests for categorical variables and t-tests for continuous ones. Normality was tested using the Shapiro-Wilk test and, when needed, continuous variables were log-transformed to improve their normality. SNPs (rs4833095 in TLR2) deviating from the Hardy-Weinberg equilibrium or showing a null MAF (rs5743708 in TLR2) were excluded. A multivariate logistic regression was performed to first ascertain the association between all SNPs and H.
Leisure horses comprised horses that were involved in various riding activities (dressage, jumping, reining, equestrian rides) with no specific purpose, as a hobby of the rider. For the second experiment, as part of the inclusion criteria, horses had to be involved in one of the following equine activities as part of their usual routine: jumping, eventing, dressage or EAA/T. These horses had been involved in one of these activities since the age of 3-4 years. To reduce the number of animals used for research proposals and to respect legislation concerning ethics and equine welfare, particularly the 3R's rule, data obtained in the first experiment concerning horses involved in jumping, eventing and dressage were used for the second experiment. Nine new horses involved in EAA/T were also included.
These phases lasted no more than 5 min each, except for the baseline phase. Horses were led and removed from the testing area between each phase by an operator. During each testing phase, the horses were free in the testing area. HRV data were collected using the Polar V800 Equine ® system (Kempele, Finland). The data collected with the Polar system were transformed with Kubios ® software (Kuopio, Finland) and only normal R-R intervals were considered for the HRV analysis. The final data included time domain and frequency domain analysis results (Table  2 ). Frequency band thresholds were established within each frequency interval using the following parameters: LF power = 0. 005-0. 07 Hz; HF power = 0. 07-0. 5 Hz; and LF/HF ratio  [32]. During the last four phases, behavioral data were collected via video recording using a Sony Handycam HDR-CX450 ® camera (Weybridge, UK).
Behaviors were assessed through video analysis, and with the help of an Excel ® matrix (Redmond, WA, USA), behavior durations were determined by one operator according to an ethogram (Table  3 ). This ethogram was developed based on the importance of these behaviors for equines  [18, 19, [38] [39] [40]. For experiment 1, raw data were used for statistical analysis, and the test was considered to last 5 min for each phase for each horse. However, most of the horses did not need 5 min to achieve the goal, so in the second experiment, each phase was considered as finished once the horse achieved the goal. As the time to achieve the goal could vary between individuals, the proportion of the duration of each specific behavior over the latency to obtain the treat was estimated. Table  1. Description of the aims of each phase of the experiment.
Experiment 1 Due to technical issues concerning the HR monitor, the data of 3 horses were not recorded. Additionally, artifacts concerning SDNN, RMSSD and the LF/HF ratio parameter of 2 horses were found. Aberrant data were excluded from the statistical analysis. Additionally, for technical reasons, the video camera did not record some time frames, and some data were absent for 1 horse and could not be considered in the statistical analysis. Some horses in the original population (one horse in phase 2; one horse in phase 3; three horses in phase 4; and two horses in phase 5) did not achieve the goal within 5 min, so their data were removed from the statistical analysis considering Latency 1. All the included horses succeeded in the habituation phase. 3. 1. 1. Physiological Data (Table  4 ) Significant differences in HR were observed between phases (DF = 4; F = 20.
Experiment 2 Due to technical issues concerning the HR monitor, the data of 5 horses were not recorded. Additionally, artifacts concerning HR, SDNN, RMSSD, and the LF/HF ratio of a few horses were found. Aberrant data were excluded from the statistical analysis. Furthermore, because of technical reasons, the video camera did not record some time frames of 1 horse, so these data were absent and could not be considered in the statistical analysis. Some horses in the original population did not achieve the goal within the 5 min, so their data were removed from the statistical analysis for Latency 1 (one horse in phase 2, one horse in phase 3, three horses in phase 4, and two horses in phase 5) and Latency 2 (three horses only in phase 3). All the included horses succeeded in the habituation phase.
Development was calculated as a percentage of late L4 and young adults in the presence of compounds of interest normalized to the untreated control. Every concentration was set-up in triplicate and all experiments were independently replicated at least five times. Curve fitting for the larval development assay (sigmoidal dose-response curve with variable slope) was performed with the Prism 6 software package (GraphPad, SanDiego, CA, USA). This allowed calculation of EC 50 values, i. e. , the concentrations at which 50% of the animals fail to reach the young adult stage.
C. elegans dye filling assay Amphidial dendrites of C. elegans in wild-type Bristol N2 and nhr-8(ok186) were visualized by DiI staining of amphids, before and after 35 weeks of drug selection pressure with IVM. Worms were synchronized at the young adult stage and larvae were incubated in a dye solution containing 10 ng/ml of DiIC 12  (3)  (1,1'-Didodecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate) in M9 with gentle shaking for 2 h at 21˚C. After a recovering period of 2 h on NGM plates, worms were paralyzed using levamisole (40 mM) and dye-filled L4s were observed using a Nikon Eclipse 50i microscope equipped with a Luca S camera and analyzed using Nikon ACT-1 software. Animals were scored for the red staining of the amphids neurons and expressed as percentage of animals with a dye-filling defective phenotype.
Following this incubation, larvae were sedimented and transferred onto a glass slide for counting. Observation of intestinal fluorescence was carried out at a magnification of x100 through a fluorescence inverted microscope fitted with a UV blue range filter (495 nm). At least 200 larvae were counted in each sample and larvae with FITC visible in the larval oesophagus and throughout the gastrointestinal tract were considered to be fed, while larvae lacking FITC labelling in the gut or with green fluorescence only around the buccal opening were considered unfed. A least two samples were analyzed for control and per drug concentration and each assay included two independent replicates. Control samples provided a qualitative measure of larval viability. Logarithm of doses against percentage of fed larvae was plotted and the LFI 50 for IVM in the presence of control RNAi or nhr-8 RNAi was calculated using the Prism 6 software package (GraphPad, SanDiego, CA, USA).
The cDNA was diluted at 2. 5X with H2O and used immediately for qPCR analysis. Quantification of mRNA expression by RT-PCR. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed using a ViiA7 Sequence Detection System instrument and software (Life Technologies, Applied Biosystems, Courtaboeuf, France). Genespecific primers for SYBR Green assays were designed according to the genome sequence of C. elegans (www. wormbase. org), using Primer Express software version 2. 0 (Applied Biosystems) and synthesized by Invitrogen (Cergy Pontoise, France). All primers were entered into the NCBI Blast program to ensure specificity. Results were expressed using the comparative Ct method as described in User Bulletin 2 (Applied Biosystem). Briefly, the ΔC t values were calculated in every sample for each gene of interest as following: C t gene of interest -C t reporter gene , with cell division cycle protein 42 (CDC42) as the reference gene.
Assay of ABC transporter-mediated xenobiotic transport in C. elegans To evaluate some active transport of xenobiotics mediated by ABC transporters in C. elegans, we used a PGP functional assay that has been developed in mammalian cells  [84]  and adapted in nematodes  [85]. Accumulation of the fluorescent PGP substrate rhodamine 123 (rho123) was investigated in adult wild-type Bristol N2 and nhr-8(ok186) C. elegans. Briefly, synchronized worms were collected in M9 and incubated in with rho123 at 10 μM for 48 h at 21˚C under gentle agitation. After a wash with M9 and a short recovery period on NGM plates, worms were picked, paralyzed using levamisole (2. 5 mM) and observed by using a Nikon Eclipse 50i microscope equipped with a Luca S camera and analyzed using Nikon ACT-1 software. Image analysis was adapted from a method previously described  [86].
Acknowledgments The authors would like to acknowledge  Dr Julie Ahringer , the originator of the library, and  Source BioScience LifeSciences  for providing the RNA interference library. We thank  Nemametrix  for help in analyzing the EPGs recordings. The authors would like to thank  Jean-Francois Sutra  ( INTHERES, INRA UMR1436 ) for HPLC analysis of macrocyclic lactones stock solutions, as well as  Yannick Lippi  and  Claire Naylies  from the  Technological Platform on Transcriptomics GeT-TRiX  ( Transcriptomic impact of Xenobiotics, INRA UMR1331 ) for access and expertise on transcriptomic studies.
HA is funded by an  ERC   consolidator grant  ( H2020/2014-2019-N˚647003 ). This work was funded by  EMIDA ERA-NET  project  CARES n1 1-EMID-003-02  and  Metaprogram GISA-Projets-Envergure/STReP. Nemametrix awarded a travel fellowship. The funders had no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.
Methods Three jumping horses (mean (SD): 556 (55) kg) clinically sound were used. After trimming, the right hind hoof of each horse was equipped with a DHS composed of 4 triaxial piezoelectric force sensors sandwiched between 2 aluminium plates  (Chateau et al. 2009). A horseshoe with matching height and weight was fixed to the left hind, as well as to both fore hooves. DHS wires were connected to an A/D converter (NI-USB) plugged in a computer remotely controlled (Wi-Fi). Data were acquired at 7. 8 kHz. The acquisition system was placed in saddle bags. GRF was calculated as the sum of forces applied on each sensor and expressed in a local reference frame with the longitudinal X axis parallel to the solar plane of the shoe (positive forward), and the normal Z axis perpendicular to the solar plane (positive downward).
3, 1. 4, 1. 3, 1. 2, 1. 1 m), twice at each lead (right/left) canter, alternatively. To delimit the stance phase, the threshold was set to a 100 N vertical force. Knowing the angle made by the right hind hoof with respect to the ground surface during stance (angle calculated using the two upper markers of the T-square, and those placed along the track), GRF on the right hind limb was projected in the track's reference frame. Customised softwares developed in Matlab (MathWorks) were used to calculate stance and stride duration as well as peak forces and impulses (integral of force over time) in the track's reference frame. Linear mixed-effects regression models (SAS v. 9. 2) were used to test the association between dynamic variables and fence's height, taken into account repetitions within a given horse, and adjusting for the lead (P < 0.
Shape analyses Pairwise comparisons show significant shape differences between the three groups in all the bones (MANOVA, p < 0. 05). The two-way MANOVA performed on the shape data does not indicate an interaction between species-specific and sexual differences in our sample except for the coxal bone. Consequently, coxal shape variation was explored in males and females independently plotting first PCs. Trangression and dominance degrees were also computed to compare with results obtained on the whole dataset but the limited size of our sample does not enable us to perform statistical tests for each sex separately (see Additional file 3). The distribution of the specimens along the first axes of the PCA reveals that, for all the bones, most of the hybrid individuals overlap with parental species (Fig.
Discussion Pattern of shape differentiation between the hybrids and their parent species Hybridization has been previously reported as able to produce an increased shape variance from the first generation hybrids onwards  [31]. In the absence of recombination between the parental genomes, this phenomenon has been related to decreased canalization in hybrids (i. e. the buffering of developmental processes against genetic and environmental variation in order to keep the phenotype constant). In our case, the absence of significant increased shape variance within the hybrid group in comparison with their parent species does not allow us to suggest that canalization is affected by hybridization in domestic equids. However, the impossibility to directly compare hybrids with their actual parents (or at least with a sub-sample comprised of the parental breeds used to produce the hybrids in our dataset) makes it impossible to discuss the potential impact of hybridization on shape variance in our sample.
Shape analyses A Principal Component Analysis (PCA) was performed on the procrustes residuals of each bone to reduce the dimensionality of the multivariate datasets  [63] [64] [65] [66]. The first Principal Components (PCs) were then plotted in order to observe the distribution of the data in shape space. The PCAs were performed using the R package "Rmorph"  [67, 68]. Shape differences between species (horses, donkeys and hybrids) were tested for each bone using Multivariate Analyses of Variance (MANOVA) with pairwise comparisons and Bonferroni corrections for multiple testing. They were performed on the Principal Components (PCs) explaining 90% of the total variance using the the "RVAide-Memoire" library  [69]. A two-way MANOVA was performed on the shape data to test the potential interaction between species differentiation and sexual dimorphism (on bones displaying a significant difference in shape between males and females).
Bonferroni corrections were conducted to adjust the p-values from each set of tests including a same bone. In addition, the z-scores (effect size) of rPLS values were computed in order to enable their comparison between datasets  [78]. This test estimates the standard deviate of rPLS values obtained from different datasets displaying different expected values under the null hypothesis of no integration (due to variations in the number of variables and sample size). The difference in the effect-sizes was then assessed using two-sample tests with Bonferroni corrections for multiple testing. These analyses were computed using the "geomorph" library  [70]. In some cases, in order to better investigate the shape covariation, the first PLS axes were plotted using the "Rmorph" library  [67]  and the associated shape changes were visualized.
Visualizations of the extreme shapes associated with the PLS axes were produced using a 3D photogrammetric model (from the bones of the modern specimen: CV9 -ONIRIS-Nantes AC, with photographs taken using a Canon EOS 700D and 3D reconstructions computed on the software Agisoft PhotoScan;© 2014 Agisoft LLC, 27 Gzhatskaya st. , St. Petersburg, Russia). The landmark coordinates of the 3D model were obtained from the "IDAV Landmark Editor"  [79]  and the shape deformation along the axes were finally visualized thanks to a Thin Plate Spline (TPS) deformation of the consensus surface, using the "Morpho" library  [72]. For all the analyses previously described, test results were considered as significant when p-values (p) were below 0. 05.
Acknowledgments We thank the morphometry platform from the  MNHN  ( UMS 2700 ) and the movement analysis platform from the  UMR CNRS/MNHN 7179  ( Paris, France ) who lent the digitizing devices. We also thank the researchers, curators and collection technicians who allowed access to the specimens:  Luc Vives ,  Joséphine Lesur ,  Christine Lefèvre ,  Aurélie Verguin  and  Céline Bens  ( MNHN-Paris );  Benoît Clavel ,  Jean-Hervé Yvinec  and  Gaëtan Jouanin  ( CRAVO-Compiègne );  Christian Bussy  ( Clinique Vétérinaire du Grand Renaud-Saint Saturnin );  Manuel Comte ,  Aurélia Borvon  ( ONIRIS-Nantes );  Benoît Mellier  ( MSN-Angers );  Philippe Migaud  ( Vetpole-Pays Mellois );  Wim Van Neer ,  Georges Lenglet ,  Sébastien Bruaux  and  Terry Walschaerts  ( IRSNB-Bruxelles );  Michael Hiermeier  ( ZSM-Munich );  Henriette Obermaier  ( SAPM-Munich );  Renate Schafberg  ( MLU/ZNS/H-Halle/Saale );  Erich Pucher  and  Konstantina Saliari  ( NHM-Wien ).
There is an historical assumption that current RDT tests in animals are predictive of effects on human health, although interspecies variability (which may reveal lack of relevance) is acknowledged when using such data for safety assessments in humans. As such, in many sectors, despite the potential limitations, the results from RDT tests are one of the cornerstones of ensuring safety of consumers, patients and for occupational exposure. Whilst the use of many standard tests of varying exposure time was acknowledged, the EPAA Partners' Forum focussed much of its attention on the 90-day assays -at the same time appreciating that these tests are not performed in the cosmetics industry. Typically the 90-day RDT test requires two species and an appropriate route of exposure, most commonly oral, but dermal and inhalation may also be required.
Dosing at a range of concentrations up to the maximum tolerated dose is performed regularly, e. g. daily, and observations are compared to a control. The observations should include clinical, histopathological, behavioural and many other measurements. Testing may also include range-finding and palatability studies, usually of short duration. Observations of endpoints in RDT tests may trigger further testing for specific effects. Details of experimental design and procedures are provided in the Test Guidelines referred to in Table  1  although there are many variations and additional requirements as summarised below. The EPAA Partners' Forum heard that, with the exception of the cosmetics industry, RDT testing is commonly performed across all industrial sectors. It is considered to provide a rich source of data and information on the effects of a chemical on an organism.
Regulatory importance, status and challenges of RDT testing The EPAA Partners' Forum heard that the use of RDT testing is governed by a multitude of regulations, directives and guidelines. The regulations cover different industrial sectors and global regions and it is inevitable that there are different requirements within individual sectors and geographies, those presented at the Forum are summarised briefly below. However, at the core of all regulations is the recognition of the use of OECD Test Guideline studies, mostly due to Mutual Acceptance of Data within and outside of OECD countries. The 90-day RDT test is frequently required due to the depth of information it provides and the understanding of the results. As well as being a regulatory information requirement, the results of RDT testing for the most sensitive species and endpoint can be used to identify points of departure (PoD), notably the No Observed (Adverse) Effect Level (NO(A) EL), Lowest Observed (Adverse) Effect Level (LO(A)EL) and, where possible, benchmark dose (BMD).
The result is a variety of requirements, some of which may even be considered contradictory with each other. Further information was provided to the EPAA Partners' Forum relating to the role of individual European Agencies in using information from RDT tests. Under the Registration, Evaluation, Authorisation and restriction of CHemical substances (REACH) regulation, the European Chemicals Agency (ECHA) has minimum requirements for data dependent on tonnage and other conditions. However, ECHA's database which is available through ECHA's dissemination portal (cf. https:// echa. europa. eu/information-on-chemicals) has many data gaps for RDT studies and, with the aim of avoiding as much animal testing as possible, the REACH regulation allows for adaptation of standard information requirements e.
Abbreviations the in vivo tests and also the alternatives. Such resources could ensure that testing is not repeated unnecessarily and could assist with the validation of alternatives. In addition, retrospective studies of data can assist in the refinement of existing tests. The challenges for the use of 3Rs in RDT for regulatory purposes were considered by the EPAA Partners' Forum and the initiatives attempting to address them are discussed in Section 2 along with opportunities in Section 3 below.
The CE-ToxGPS platform develops further the COSMOS database (https://cosmosdb. eu/cosmosdb. v2/) and is intended to extend the role of the system from data storage to data integration with active workflows and inclusion of predictive capabilities to help risk assessors. Related to cosmetic products, the safe use of fragrance materials is ensured by the fragrance industry's self-regulatory programme through its members and affiliates IFRA and the Research Institute for Fragrance Materials (RIFM) Inc, in which scientific data are generated, evaluated and distributed for the safety of fragrance raw materials found in personal and household care products. In order to determine safety, a four step procedure with evaluation from an Expert Panel is applied  (Api et al. , 2015)  and the findings are made available through the Food and Chemical Toxicology Fragrance Material Safety Assessment Centre  (RIFM, 2019).
Methodological development The cross-sector EPAA Partners' Forum was in agreement that there are various opportunities for the development of all areas of RDT methodology from test design to the reporting of outcomes. The clear opportunity here is to align new research (and hence funding may be required) for better problem formulation to support the overall goal of safety to humans. The main areas to be considered were summarised as being with regard to the information and data derived from RDT and related studies, the integration of the data to provide a solution and use of appropriate benchmarks to provide assurance of the outcome. In terms of the design of RDT various adaptions could be foreseen aligned to the better design of the test. These could be to take account of preliminary information from e.
Data sharing The sharing of data across sectors was seen by the EPAA Partners' Forum as a very large opportunity to progress the 3Rs for RDT. There are a number of aspects to this. The first is the sharing of the results of RDT tests themselves to provide access to more data which would prevent the need for repeat and unnecessary testing. In addition, a good data source will provide the basis for models as well and the evaluation and eventual validation of alternatives. The sharing of data should also extend beyond the standard tests to include data for toxicokinetics, alternatives, omics analyses, mechanistic information and data from human clinical trials, amongst others. Such an (ambitious) data framework may allow ultimately for the assurance of no human toxicity from non-clinical data.