dataesr/scientific-paragraphs-categorization huggingface dataset:
Fitting evaluation of candidate models relating cumulative feed intake (kg) or time (d) to cumulative bodyweight gain (kg): median (IQR) of the calculated R 2 Bayes and WAIC for each model. Each model was fitted separately to each training dataset of each individual pig (Population A: n ¼ 32 pigs; Population B: n ¼ 30 pigs). For R 2Bayes , values closer to one indicate that the model provides good fit to the data. For WAIC, lower WAIC indicates a model that fits better and is more parsimonious. For description of the dataset see Table1.
Forecasting evaluation of candidate models relating cumulative feed intake (kg) or time (d) to cumulative bodyweight gain (kg): median (IQR) of the calculated MAPE Bayes (%) for each model. Each model was fitted separately to each training dataset of each individual pig (Population A: n ¼ 32 pigs; Population B: n ¼ 30 pigs), followed by trend forecasts tested on each validation dataset of each individual pig. Forecasts were generated over forecast horizons H ranging from 1 to 30 d. For MAPE Bayes , percentage values closer to zero indicate smaller predictive error.
Acknowledgements This study was funded in part by the  Biotechnology and Biological Sciences Research Council  in collaboration with AB Vista in the form of a postgraduate studentship to M. M. M. This paper is a part of M. M. M. 's doctoral thesis. J. A. N. F. , L. B. and I. K. were supported by the Feed-a- Gene  project. Feed-a-Gene received funding from the  European Commission  under the  European Union Framework Programme for Research and Innovation Horizon 2020  under grant agreement no. 633531. J. A. N. F. was also partially supported by The  Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS). The authors would like to thank  Dr Egbert Knol  for providing additional sources of data.
Forwhere each individual pig, we assessed the goodness of fit of the models to a training dataset, through a Bayesian coefficient of determination, R 2 Bayes based on the variance of the errors of the fitted model (Gelman, Goodrich, Gabry, & Vehtari, 2019): Yare the Nobservations from the given animal and b Y are the fitted model values corresponding to a single parameter point in the MCMC sample. The median of R 2.
(EGFR) dimerizes and autophosphorylates itself, changing the conformation of its intracellular domain. Adaptor proteins are consequently recruited to initiate a RAS-driven MAP kinase signaling cascade that controls numerous events, including cell survival, proliferation, differentiation, growth, migration, and resistance to apoptosis  23, 24. Here, we focus on kinases as potential anthelmintic targets for several reasons. First, there is extensive knowledge of kinase structure. The structures of protein kinases are among the most intensely studied of any protein family  25  (http:// www. thesgc. org/ scien ce/ prote in-kinas es/); the Protein Data Bank (PDB) contains over 7000 kinase structures with and without inhibitors bound  26  (http:// www. rcsb. org/). The vast number of solved kinase structures is likely due to their key roles in both development and pathogeneses, but also because of the relative ease of kinase purification and in vitro biochemical assays.
This divergence could then be exploited to develop nematode-selective inhibitors. To do this, we first used the SWISS-MODEL pipeline to generate protein homology models, mapping the C. elegans primary sequence onto the experimentally derived 3D crystal structure of the respective vertebrate kinase ortholog  41. These homology models were visualized using PyMOL (The PyMOL Molecular Graphics System, Version 2. 1. 1, Schrödinger, LLC). To test the validity of a homology modeling approach, we first created a homology model of the C. elegans LET-23 kinase domain based on the solved structure of the orthologous human EGFR kinase domain (Protein Data Bank (PDB) structure 2ITX 42 ) (Supplementary Fig. 1A ). We then compared the LET-23 homology model to the experimentally derived crystal structure of the LET-23 kinase domain (PDB: 5WNO  43  ; Supplementary Fig.
Together, these results show that MEK-2 may be an excellent anthelmintic target. Divergence of the MEK-2 hinge may be exploited to develop nematode-selective inhibitors. The commercial MEK1/2 inhibitors that we screened are allosteric modulators that do not compete for the ATP binding pocket (Fig. 6 ). Instead, they bind near the base of the αC helix, which is distal to the divergent nematode sequence in the hinge region (Fig. 6B ; PDB: 3PP1  58  ). It is therefore unlikely that these allosteric MEK inhibitors can be modified to be nematode-selective. By contrast, MEK1/2 ATP-competitive inhibitors may be far better scaffolds upon which to build nematode-selective analogs because the hinge that lines the ATP-binding pocket of nematode MEK-2 is divergent from that of vertebrate MEK1/2 (Fig. 6B ).
We investigated whether the differences in nematode MEK1/2 structure are likely sufficient to confer phylum-selectivity. We first inspected the co-crystal structure of an ATP-competitive inhibitor of MEK1/2 called BI-847325 (PDB: 5EYM)  59  , which binds to the vertebrate MEK1/2 close to the hinge region (Fig. 2B ). Inspection of the MEK-2 homology model reveals that the leucine of the nematode sequence (G149L) may sterically hinder BI-847325′s terminal amine and prevent binding (Fig. 2B , Supplementary Fig. 2B ). Of note, BI-847325 is one of the only established MEK1/2 selective inhibitors that competes for the ATP-binding pocket; the majority of MEK1/2 inhibitors are non-ATP competitive allosteric modulators  60. We tested the hypothesis that BI-847325 is unable to disrupt MEK-2 activity in vivo through a dose-response analysis.
We modeled the protein structure of C. elegans PLK-1 against the crystal structure of human PLK1 (PDB:2RKU)  64. Four residues in the ATP binding pocket differ between C. elegans PLK-1 and human PLK1 (Fig. 2C , Supplementary Fig. 2C ). A multiple sequence alignment with additional nematode and vertebrate species shows that nematode residues differ at each of these locations, with a greater degree of conservation with the specific C. elegans amino acid among the parasitic Clade V nematodes (Fig. 2C′ ). A fifth residue of interest was identified (R57) that is conserved between C. elegans and vertebrates but differs in a number of the parasitic nematode sequences examined (Fig. 2C′ ). We retested a selection of available PKIS compounds from the three core scaffolds of interest in C. elegans and two additional free-living nematode species, C.
For the PKIS library, we used the published in vitro kinase inhibition data to assign kinase targets to each inhibitor hit  [35] [36] [37]. For hits from PKIS1, any kinase that was inhibited ≥ 65% at 0. 1 μM compound concentration was considered a target. For hits from PKIS2, any kinase that was inhibited ≥ 90% at 1 μM compound concentration was considered a target. If there were more than 10 kinase targets for a particular PKIS inhibitor Homology modeling and sequence analysis. Caenorhabditis elegans orthologs of human kinases targeted by our inhibitors were identified using OrthoList 2  81. C. elegans kinase protein structure homology models were generated using the SWISS-MODEL pipeline using the indicated structural templates accessed from the Protein Data Bank (PDB)  41. At least two unique human kinase templates were used for modeling each nematode kinase ortholog if available.
Acknowledgements The  Ontario Institute for Cancer Research (OICR)  Kinase Inhibitor Library was provided by  Rima Al-Awar  and  David Uehling  at  OICR. The APExBIO DiscoveryProbe Kinase Inhibitor Library was provided by  Jim Dowling. The GSK Published Kinase Inhibitor Set (PKIS) molecules were provided by  William Zuercher. We are grateful for the gift of the humanized LET-23 C. elegans strain from  Dr. Jaegal Shim  and to  Prof. Tim Geary  for helpful conversations. Some C. elegans strains were provided by the  CGC , which is funded by  NIH Office of Research Infrastructure Programs  ( P40 OD010440 ). This work is supported by a  CIHR grant  ( 313296 ) and a  Canada Research Chair in Chemical Genetics  to PJR, an  NSERC   Alexander Graham Bell Canada Graduate Scholarship  to JK, an  NIH  grant ( R01GM109176 ) to  N.
Causal agents of schistosomiasis are dioecious, digenean schistosomes affecting mankind in 76 countries. Preventive measures are manifold but need to be complemented by vaccination for long-term protection; vaccine candidates in advanced pre-clinical/clinical stages include Sm14, Sm-TSP-2/Sm-TSP-2Al ® , Smp80/SchistoShield ® , and Sh28GST/Bilhvax ®. Natural and anthropogenic changes impact on breaking species isolation barriers favoring introgressive hybridization, i. e. , allelic exchange among gene pools of sympatric, interbreeding species leading to instant large genetic diversity. Phylogenetic distance matters, thus the less species differ phylogenetically the more likely they hybridize. PubMed and Embase databases were searched for publications limited to hybridale confirmation by mitochondrial cytochrome c oxidase (COX) and/or nuclear ribosomal internal transcribed spacer (ITS).
The occurrence of ShxSb crossbreeds in Europe with a likely West African origin was decisive for an in-depth investigation of published reports on natural human hybridale schistosomes among databases of PubMed and Embase in addition to considerations on prevention of schistosomiasis through vaccination based on aforementioned leading candidates. Hybridization of schistosomes could be suspected by ectopic egg elimination, e. g. , excretion of Sm eggs also in the urine, or visualization of the egg morphology, i. e. , eggs having an intermediate morphology between two species. However, both are not sophisticated markers. Ectopic eggs could be indicative of alternate routes of excess egg excretion, and as the egg shape of first generation F1 hybrids and mother species is identical hybrid ancestry cannot be confirmed either  [56].
Though Southern Europe was regarded as parasite-free since the 1950s-1960s, ShxSb crossbreeds were found among urinary ova of a 12-year-old boy from Corsica, France; he likely got infected during recreational activities near Corsican rivers, e. g. , Cavu River, during a large schistosomiasis outbreak during summer 2013  [75, [86] [87] [88] [89]. Isolates revealed three haplotypes among COX1 amplicons with 0. 21% sequence divergence, and 98. 43-99. 48%, 93. 19-94. 97%, 88. 90-90. 16% and 98. 22-98. 85% sequence identities with Sb, Sc and Sh, respectively, from Sô-Tchanhoué and Toho, Benin, and Melen and Ekouk, Gabon, and GenBank data. Three haplotypes detected among ITS2 fragments showed 99. 98% sequence identity; haplotype-1 and -2 harbored Sh SNPs, i. e. , guanine-cytosine-guanine, at the polymorphic positions 25, 80 and 130, whereas haplotype-3 harbored a single SNP, i.
In Côte d'Ivoire, ShxSm hybrids were not detected before, except for travelers returning from the coastal country that sought healthcare in hospitals in France. Viable miracidia of urinary but not fecal ova of a male child with a stay in Divo, Côte d'Ivoire during summer 2007 revealed 25 equally intense, double chromatographic peaks among DNA amplicons using the 28DNA (partial nuclear ribosomal 28SDNA) marker; they were identical to polymorphic positions of Sm and Sh reference templates from GenBank clearly indicating crossbreeding  [47]. COX1 showed 99. 1% sequence homology with Sm revealing their maternal inheritance. Eggs isolated from urine likely occurred due to hybridization of female Sm with male Sh, which is unexpected due to their high phylogenetic distance. However, as co-infections due to species sympatry with male competitiveness for females, and males determining the oviposition site are reported, natural heterologous interactions are possible  [109, 110].
Describing and analysing LBW management practices is the first step in reducing the high mortality rates confronting them. In production animals, survey-based studies have been conducted to provide better understanding of newborn management practices, their determinants and their consequences  [13] [14] [15] [16] [17] [18]. They provide a basis for evaluating current practices and targeting communication and teaching for their improvement. To our knowledge, and despite LBW being a major canine and feline health concern, the management practices and the beliefs of breeders regarding LBW have never been the subject of any scientific study. The objective of this study was thus, for the first time, to identify canine and feline breeder profiles regarding LBW management (i. e. , groups with similar management practices) based on data collected through a large online survey.
Survey Design A collaborative meeting was first organised between five veterinarians specialized in carnivore neonatology and 15 French canine and/or feline breeders to explore the management of newborns in their facilities. An online questionnaire was then drafted in French using the software Sphinx iQ 2 (Le Sphinx, Chavanod, France) and pretested by 10 people. The survey was launched in September 2019: the link was sent to dog and cat breeders belonging to the NeoCare network via Facebook and an internal mailing list (n = 3743 and n = 910, respectively). This network is made up of breeders who have voluntarily signed up to receive newsletters about the work of the team. The survey was also shared without our control. At the beginning of the questionnaire, participants were informed about the anonymity and confidentiality of the data they provide, and that by completing the questionnaire they were giving their consent for their answers to be analysed.
Discussion Despite the clear relationship between LBW and neonatal mortality  [4] [5] [6] [7] , to the authors' knowledge, this work is the first to explore practices and perceptions of canine and feline breeders regarding LBW neonates. Knowing current practices is the first step towards targeting communication and teaching to improve them with the final objective of reducing puppy and kitten neonatal mortality. Data were collected from 674 breeders. This population represents less than 2% of the total number of active breeders referenced in France (according to the Société Centrale Canine and the Livre Officiel des Origines Félines, LOOF  [23] ). Figure  1  shows that the respondents were distributed throughout France but in a heterogeneous way with a concentration of breeders around Paris and in the south of the country.
This distribution is consistent with, on the one hand, the distribution of cat breeders detailed by LOOF  [23]  and, on the other hand, with that of dog breeders estimated using the data of the Breeding Management System software (BMS, Royal Canin SAS, Aimargues, France; n = 3027 kennels; unpublished data). The respondents were recruited on a voluntary basis, mostly via Internet. Thus, a selection bias cannot be ruled out and younger breeders (more familiar with the Internet) and/or with more efficient management of LBW and/or already aware of LBW as an issue regarding neonatal mortality, were potentially more likely to respond to the survey. As this survey was written in French, the respondents were mostly French or from French-speaking countries. Further studies are needed to explore the differences in management and perceptions in other countries.
At D15, D28, D61 and D104, the pigs were individually weighed and the average daily gain (ADG) was calculated for the suckling period from D15 to D28, for the nursery period from D28 to D61 and for the growing period from D61 to D104. Feed intake was recorded at the half room level (included five pens as one unit) and the food conversion ratios were calculated. However, as the treatments were balanced between the rooms, these data were not available for each treatment.
Statistical Analysis Raw comparisons between treatments were carried out using non-parametric tests based on the ranks (Wilcoxon test during the farrowing period and Kruskal-Wallis test during the nursery and growing periods) for algae consumption and the number of marked pigs manipulating the materials. Frequencies of lesions were compared with the χ 2 test. Correlations between the material consumption at the three periods were calculated as the Spearman correlation coefficients based on the ranks. If a "batch" effect was detected, batches were analyzed separately. For multivariate modeling, enrichment material type (A vs. C from D15 to D28; A, W or MC from D29 to D104) was introduced as a fixed factor. A mixed ANOVA model with the pen as random effect was used to analyze, for observations on behavior (scans), the number of pigs manipulating the material and the individual weight, ADG, cortisol levels (R software, package geepack).
For comparison purposes, behavioral counts in a pen were weighted to obtain counts on 10 pigs. Cortisol concentrations were log-transformed. Post-hoc tests were carried out using Tukey's range tests. The risk of being injured (lesion) was modeled using a logistic regression model, introducing enrichment material and sex as the fixed effects; the litter effect was taken into account in a mixed model with the pen (a litter was housed in a single pen) as a random effect (package lme4). Repeated measures of lesions from D28 to D104 were taken into account with a repeated mixed regression model.
Acknowledgments: The authors thank the  Brittany Regional Council  and the  Ministry of Agriculture's Animal Protection Office  for their financial support. They also thank the staff from the  Crécom experimental farm , the technical staff of EPISABE unit of the  ANSES Ploufragan Laboratory  and the  Algopack company  for their technical support. They are also grateful to  Armelle Prunier  from  INRA, UMR PEGASE , and her staff for their help in cortisol analysis.
Heart rate measurement Commercially available heart rate (HR) meters were used for the HR measurements (Polar M400 Equine, Polar Electro GmbH, Buettelbronn, Germany). The HR meters were attached to the thorax of the horses according to the manufacturer s instructions. The HR was recorded at 5 s intervals. The data recorded by the HR meter were transferred to a computer for analysis with Polar Equine Software (Polar Electro, Finland). The mean HR during each interval was plotted linearly against the speed of the interval and v180 calculated from this relation (v180 = velocity run under defined conditions inducing 180 beats/min). The number of v180 values was lower than the number of v4 values because of missing data from the HR meter recordings.
Siwinska et al. [14]  reported proportions of sand in stool but did not evaluate the corresponding level of ingestion. Thus, the ingestions of soil and sand by horses and its pathologic consequences has been clearly shown but no available data allows more accurate evaluation in horses. Animals of comparable size, such as adult cattle, may ingest 30 to 100 g of dry soil per 100 kg of BW daily  [3, 6]  under classical pasture conditions, and even up to 150 g per 100 kg of BW under poorer conditions  [4, 15] , but the grass prehension differs notably between both species. Indeed, the height of the available grass is objectively measured with a herbometer and expressed as sward height (SH). It has been shown in ruminants that sward height (SH), especially post-grazing, is a good predictor of the level of soil ingestion  [4, 6].
Statistical Analyses Statistical analyses were performed using R software, version 3. 6. 1  [22]. Intake variables (grass and total intakes, faecal output, DM digestibility), body weight and soil ingestion variables (fecal AIA content, SIR, QIS), were tested using Linear Mixed Models (LMM) with treatment, period and treatment × period interaction as fixed effects, and individual as a random effect. A non-significant interaction between treatment and period was removed from final models. Each horse represented an experimental unit. Significant effects were declared at p < 0. 05 but tendencies (i. e. , p < 0. 10) were also indicated. Multiple comparisons for each significant factor were realized using Tukey correction (p < 0. 05) with glht function of multcomp package.
Statistical analyses. At least four replicates per concentration were included in all experiments. The results on phenolic content are expressed as mean ± standard error of the mean (SEM). Anthelmintic data are expressed as the concentrations inhibiting 50% of larval exsheathment or egg hatching (IC 50 values, µg mL -1 ), and 95% confidence intervals (CI), obtained by Probit analysis. SPSS Statistics v. 26. 0 software was used to assess significant differences among IC 50 values, through relative median potency estimates, and among phenolic data, by one-way analysis of variance (ANOVA) followed by the post-hoc Tukey HSD test. Spearman correlations were calculated between the total flavonoids, total phenols, and the IC 50 values for LEIA on the 2 nematode species.
Sequence alignment and phylogenetic analysis Obtained sequences were visualised in BioEdit 7. 0. 9. 0 software  (Hall 1999) ; they were then assembled using MEGA 10. 1. 8 (Kumar et al. 2018). Ambiguous bases were clarified and called using the corresponding chromatograms. Nucleotide sequences were aligned using the Clustal W option of MEGA 10. 1. 8. A BLAST search was carried out for each DNA region  (Altschul et al. 1997). Maximum Likelihood (ML), Neighbour Joining (NJ) and Minimum Evolution (ME) methods were conducted for separate and combined nucleotide data sets with other Heterophyidae sequences using MEGA 10. 1. 8. The trees were built with outgroups from the superfamily Opisthorchioidea (Table  2 ) and using 1000 bootstrap replications. Similar trees were observed, ML trees giving higher bootstrap values are shown.
Molecular identification and phylogenetic data PCR on the cox1 gene of mtDNA was performed on 29 parasites: 15 isolates from infected whiting and 14 isolates from infected Atlantic cod. PCR products were about 320 bp long. Likewise, PCR of the ITS region of rDNA from 28 parasites including 10 isolates from whiting and 18 isolates from cod resulted in a product of about 1700 bp. Sequences of the cox1 gene and ITS region were deposited in GenBank under the accession numbers MW542531-MW542559 and MW544112-MW544139, respectively. BLAST analysis of the cox1 fragments (281 bp) led to 100% of similarity with GenBank accession nos. KJ711861, KJ711862, KJ711865, KJ711866 (C. lingua, Baltic Sea, Denmark) and EU876519 (C. lingua, Canada) for 24 sequences. Four sequences had 99. 69% similarity with the KJ711866 sequence, each at Trees based on nucleotide sequences of the cox1 gene (281 bp) and the ITS region (1708 bp) showed that all sequences clustered with C.
Experimental infection of final hosts to study the growth and development of intermediate-stage parasites is laborious and requires laboratory animals. Moreover, specific determination of larval stages based on morphological traits remains difficult, subjective and ambiguous due to the lack of reproductive system traits. Molecular identification to confirm the morphological identification of isolates is strongly recommended. Few sequences are available for the Cryptocotyle Fig. 4  Phylogenetic trees based on cox1 mtDNA (left tree) and ITS rDNA (right tree) sequences using the ML method with 1000 bootstraps genus in databases  (Blakeslee et al. 2008; Borges et al. 2015; Casalins et al. 2020; Duflot et al. 2021b; Tatonova & Besprozvannykh 2019). In this study, ITS and cox1 DNA sequences of C.