dataesr/scientific-paragraphs-categorization huggingface dataset:
Strategy for the Definition of Compound-Specific Human-Biota TTC In this section, the strategy for obtaining HB-TTC specific for each chemical is described (Figure  4 ). Unlike what has been described so far, the approach uses specific ecoand toxicological data for each chemical considered, instead of the profilers for the Verhaar and Cramer classes. As for the general approach, each chemical was characterized by name, CAS number, and SMILES. This facilitates the search for compounds of interest in both datasets and allows the use of in silico models to predict missing data. The PNEC value from the EnviroTox database was used directly for the assessment of the ecotoxicological properties while a more complex approach was applied to obtain quality standards for human health. For the identification of carcinogens, chemicals with a defined oral slope factor (SF) in the the IRIS and RAIS lists were considered carcinogenic and those with no SF value were considered non-carcinogenic based on the available data  [62].
As for the general approach, each chemical was characterized by name, CAS number, and SMILES. This facilitates the search for compounds of interest in both datasets and allows the use of in silico models to predict missing data. The PNEC value from the EnviroTox database was used directly for the assessment of the ecotoxicological properties while a more complex approach was applied to obtain quality standards for human health. For the identification of carcinogens, chemicals with a defined oral slope factor (SF) in the the IRIS and RAIS lists were considered carcinogenic and those with no SF value were considered non-carcinogenic based on the available data  [62]. In the case of noncarcinogenic toxic chemicals, the acceptable daily intake (ADI), the tolerable daily intake (TDI), the oral reference dose (RfD) or the benchmark dose can be used directly as human toxicological standard while the NOAEL values need to be processed as described in Equation (  2 ): TL = NOAEL/100 (2) For carcinogens, the QS was set equal to the drinking water concentration corresponding to a cancer risk level of 1 in a million (1 × 10 -6 ) additional case as acceptable cancer risk level.
This toxicological value was retrieved from the IRIS database or derived from the slope factors from the Risk Assessment Information System (RAIS)  [76]  with Equation (  3 ): QS = [(1 × 10 -6 /SF) × bw ]/wu (3) where 1 × 10 -6 is the acceptable cancer risk, SF is the oral slope factor, bw is the body weight (70 kg) and wu is the daily water uptake (2 L). As example, a dataset of 410 chemicals was processed. This dataset included chemicals present in both EnviroTox and NOAEL databases in order to retrieve easily the eco-and toxicological properties of interest. As for the general approach, the HB-TTC specific for each chemical was defined by comparing the eco-TTC and the hTTC-derived quality standards and selecting the lowest values between them.
Data Availability Statement: The list of compound-specific HB-TTCs is available on Zenodo as "Baderna, Diego, & Benfenati, Emilio. (2021). Curated Envirotox database and compound specific Human-Biota TTC from the LIFE+ Vermeer project (Version 1. 0) [Data set]. Zenodo. http://doi. org/ 10. 5281/zenodo. 4643745".
Apart from the time spline, we did not specifically take into account the temporal autocorrelation between successive GPS locations of the same individual. To describe the post-capture pattern of temporal variation in the two metrics, we modelled a smoothed effect of time since capture, based on thin plate regression splines, which differed among capture methods. We used Akaike's Information Criterion corrected for small sample size (AICc), AIC weights (AICcWt) and the number of parameters to select the most parsimonious model that best described the data  [47]. We fitted models with the 'gamm4 function in the 'gamm4 R package  [48]. Based on the selected models for the two movement metrics, we estimated the number of days it took for roe deer to attain the average distance to the centre of gravity and the distance between successive locations for each capture method.
Funding: The study was supported by grants from the Swedish Environmental Protection Agency, the "Marie-Claire Cronstedts Stiftelse" and the Swedish Infrastructure for Ecosystem Science (SITES) (UAB, PK) by the "Mov-It" ANR project (ANR-16-CE02-0010-02) to AJMH and NM, and Autonomous Province of Trento to FC. Institutional Review Board Statement: All capture and marking procedures in Aurinac, France, were done in accordance with French and European laws for animal welfare (prefectural order from the Toulouse Administrative Authority to capture and monitor wild roe deer and agreement no. A31113001 approved by the Departmental Authority of Population Protection). The research program in the Bavarian Forest, Germany, is managed by the Administration of the Bavarian Forest National Park. Game captures were conducted in accordance with European and German animal welfare laws.
| INTRODUC TI ON [7]  Most horse racing regulatory authorities have distinct frameworks for doping control and medication control. ] [10]  For medication control of drugs like flunixin meglumine, an irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC)   are estimated in order to guarantee fair competition in parallel to proper veterinary care. The IUC and IPC are determined via the Toutain model approach based on PK/PD analysis of available data (efficacious dose and corresponding plasma and urine disposition), as per the recommendation of the European Horserace Scientific Liaison Committee (EHSLC). 10 ropean Horserace Scientific Liaison Committee defines detection time as the interval between the time of the last administration and the time at which the observed urine (plasma) concentrations are below the screening limit (SL).
IUC was obtained by multiplying flunixin IPC by the corresponding Rss estimated via the model. 10 nte Carlo simulation was used to generate plasma and urine concentrations of a virtual population of 5000 horses using individual predictions (IPRED) (eta was as estimated), corresponding to 1. 1 mg/ kg single and multiple (q 12 h and q 24h for 5 days respectively) administrations. Using this meta-population, the detection time corresponding to the time of last administration under the International Federation of Horseracing Authorities (IFHA) international screening limit (ISL) in plasma (1 ng/mL) and urine (100 ng/mL) was estimated. 16 ese data were then analysed with the Phoenix statistical tool in order to compute the quantiles of interest (5, 10, 25, 50, 75 90, 95th). In the US, the Racing Medication and Testing Consortium (RMTC) compute withdrawal time with its confidence interval as done for drug residues in food-producing animals.
| D ISCUSS I ON The pharmacokinetics of flunixin were previously reported in several studies,  13, 14, 18, 19  but its population pharmacokinetics in horses remain to be established. The average steady-state volume of distribution and clearance reported were 0. 137-0. 157 L/kg and 0. 046-0. 062 L/kg/h, respectively, similar to our results. 13, 14 The numerical value of the Rss is rarely mentioned in the literature, but the average Rss value obtained herein (Rss = 37) seems consistent with those deduced from published raw data or corresponding flunixin depletion curves. 13 For convenience of urine collection, only female horses were used in this study. We believe that this has no impact on the generality of our results as no sex differences in flunixin disposition have been reported. Flunixin clearance was significantly lower in old compared with young horses.
The use of rescue medication (paracetamol 500 mg tablets; B 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated. Conclusions: A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile. Trial Registration: ClinicalTrials. gov identifier: NCT03200288. We conducted a prospective, doubleblind, 24-week study to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-tosevere symptomatic knee osteoarthritis.
Study Design This was a 24-week, phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study (ClinicalTrials. gov identifier NCT03200288) comparing the clinical performance and safety of a single i. a. injection of HA-HL with a single i. a. injection of placebo (saline) in the treatment of pain in symptomatic knee osteoarthritis. Participants were recruited among outpatients of public/private/university clinics and/or hospitals in Belgium, Germany, Hungary, Italy, and Poland. The trial protocol is available at https:// clinicaltrials. gov/ct2/show/NCT03200288. The trial protocol was approved by the local Ethical Committee of each participating site and the National Regulatory Authorities of Italy, according to the specific national regulation. The full list of institutional review boards/ independent ethics committees that approved this study can be found in the Supplementary Material.
Treatments and Randomization Eligible subjects were randomized to a single i. a. injection of HA-HL or placebo (buffered sterile physiological saline solution). Subjects were assigned sequentially into one of two parallel treatment groups in a balanced 1:1 ratio within each site using a computer-generated randomization list prepared by the Randomisation Manager using validated SAS Ò software. A strict protocol of data management, confidentiality, and access to the randomization list was followed. In addition to randomization, a number of measures were taken to minimize bias. The patients and the performance evaluator were blinded to treatment group assignment and, in recognition of the different viscosities of HA-HL and the placebo solutions, the physician who performed the injection (injector) was in all instances different from the physician who performed the efficacy and safety assessments (evaluator) and never evaluated the clinical status of patients or study parameters.
Statistical Methods The sample size calculation was based on findings from a prior registration study of HA knee injection study (IBSA data on file) that showed a 13-week difference in pain score between treated and placebo groups of 6. 39 mm (two-sided p value, 0. 0374). Based on the normal distribution with a two-sided alpha level of 0. 05, a power of 0. 80 and a 1:1 ratio of treated to placebo patients, a total sample size of 606 patients (303 assigned to treatment and 303 assigned to placebo) was calculated to demonstrate superiority. Considering a dropout rate up to 15%, a sample size of 720 patients was initially proposed. However, enrolment was stopped before reaching the 720 enrolled patients, considering the low dropout rate. Analysis of the primary efficacy endpoint was performed in the intent-to-treat (ITT) population, and sensitivity analyses were repeated in the per-protocol (PP) population.
The VAS knee pain score was analyzed using a mixed model for repeated measures approach, including treatment*time interaction, site, treatment*site interaction, baseline score, visit, and treatment*visit. A first-order autoregressive covariance structure was used. If the treatment*site interaction term was not significant (p [ 0. 15), it was removed from the model. A set of hierarchical analyses 2  was derived from slices based on visits to test the effect at each visit. Analyses of available and imputed data were performed separately for each visit on both absolute and change from baseline data. The safety analyses were performed in the safety population (which coincided with the ITT population). Hypothesis testing was carried out at the two-sided a = 0. 05 level when comparing subsequent assessment time points and/ or treatments.
12-1 rev. 6 and amendments, and all relevant local legislation in force on the conduct of clinical investigations with medical devices in OA  [19] [20] [21] [22] [23] [24] [25] [26] [27] [28]. All patients provided written informed consent. Data Availability. The datasets generated during and/or analyzed during the current study are available on reasonable request. All requests should be made in writing to the corresponding author. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4. 0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
ACKNOWLEDGEMENTS Funding. Funding for this study and the journal's Rapid Service Fee were provided by  IBSA Institut Biochimique S. A. , Lugano, Switzerland , who also provided funding for the statistical analysis, conducted by  Fred Hoeler. Medical Writing Assistance. We thank  Ray Hill , an independent medical writer, who provided medical writing support funded by  IBSA Institut Biochimique S. A. , Lugano, Switzerland. Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
(6). Among hooded seal strains previously typed by MLVA16 (3), we selected for wholegenome sequencing (WGS) B. pinnipedialis strain 23a-1, constituting a single specific genotype in the MLVA16 C3 cluster (https://microbesgenotyping. i2bc. paris-saclay. fr/ databases/public) (3). This strain was isolated from a hooded seal found in the Northeast Atlantic Ocean in Norway (3). The genomic DNA was extracted from the trypticase soy agar with 0. 6% yeast extract (TSAYE)-cultured strain with the DNeasy blood and tissue kit (Qiagen, Les Ulis, France). WGS and library construction were performed by GenoScreen (Lille, France), using the PacBio Sequel platform. The sequencing libraries were generated with a SMRTbell template preparation kit v3. 0. SMRT Link (v5. 1. 0. 26412) was used for quality control and filtering, which resulted in 127,654 subreads with an average length of 6,868 bp and an N 50 value of 8,281 bp.
sizes of 2,120,314 bp and 1,192,109 bp and with a deduced G1C content of 57. 3%, as seen for other Brucella species. WGS confirmed the specific MLVA16 genotype of strain 23a-1, and the deduced ST in MLST21 was ST54. The PacBio technology also allowed identification of the distribution of the genus-specific insertion sequence IS711  (8). A total number of 32 IS711 elements were identified, dispersed on both chromosomes. In addition, the lack of a 67-kb DNA fragment flanked by IS711 elements located on chromosome 2, relative to B. pinnipedialis strains from other seal species (9), was confirmed. Data availability. The complete genome sequence of B. pinnipedialis strain 23a-1 can be retrieved from the European Nucleotide Archive within BioProject PRJNA664313, with assembly accession number GCA_015624465 (accession number CP061816.
Experiment 2 At 70 days of age, 45 male piglets (Piétrain x (Large White x Landrace)) were transferred to the experimental stables (individual housing, concrete oor, water freely available) and fed a commercial fattening diet until the start of the experiment. Two vaccinations with Improvac ® (2 mL, subcutaneous application, Zoetis Florham Park, NJ, USA) were given at 77 and 112 days of age. At 84 days of age, the pigs (within the litter) were allocated to 3 groups of 15 animals receiving one of the experimental diets (i. e. HNE, MNE, and LNE) in pelleted form, with a progressive transition that lasted for 5 days. During the experiment, pigs were fed individually 3-times per day at 9 h, 12 h, and 15 h. Daily meals were prepared in buckets containing the expected ad libitum feed intake for 3 or 4 days plus 10% (calculated according to INRA Porc software  [15] ).
Histological and immunohistochemical evaluation of intestinal segments Tissue samples from the intestinal segments collected in Exp. 2 were embedded in para n and histological sections (5 µm thick) were cut and stained with hematoxylin-eosin (H&E). Morphometric analysis was performed as described in detail by Bilič-Šobot et al. [20]  using a Nikon Microphot FXA microscope equipped with a DS-Fi1 camera and the Imaging Software NIS Elements D. 32 (Nikon instruments Europe B. V. , Badhoevedorp, The Netherlands). For each tissue sample of the small intestine, 20 villi and 20 crypts were examined at 100× magni cation for villi width, villi height, villi perimeter, and crypt depth. Additionally, villi surface area, the thickness of intestinal mucosa, and the ratio between villi height and crypt depth were calculated  [20].
1 and used in the calculation of BW gain to NE intake ratio (G:NE). The energy values of experimental diets, average daily feed intake (ADFI) and G:F were calculated on 100% DM and subsequently adjusted to 89% DM content. Dressing percentage was calculated as the ratio between HCW and nal BW, measured 24 h before slaughter without prior fasting. Gonadosomatic index (%) was calculated as testicular weight (weight of right and left testis including epididymis) divided by nal body weight. Analysis of variance was performed using the mixed model procedure of SAS (PROC MIXED, SAS Inst. , Cary NC, USA). Repeated measurements of digestibility and nitrogen balance data (n = 8) in Exp. 1 were evaluated by including the xed effects of diet group and stage and their interaction and the random effect of pig (included in the repeated statement).
In Exp. 2, the effect of the diet (NE concentration) on growth performance was evaluated considering the xed effects of dietary treatment and litter for the phases before (day 84 to day 114) and after immunization (day 115 to day 170). For the phase after the effective immunization, two 4-week periods were looked at separately, and the model included dietary group, period, their interaction, and litter, with a pig as a repeated variable. Because the effect of immunocastration on growth performance is now well established and was not the focus of the present study, comparisons of phases before and after immunization periods are not presented. To predict the voluntary energy intake, data from the DM feed intake measurements per week, energy (ME and NE) content of the diets, and BW from the age of 84 day onwards were used to calculate relationships between cumulative energy intakes (y; ME or NE) and BW according to the following model: If age < 112 d: If age ≥ 112 d: with a diet before V2 and a diet after V2 the slopes of the relationship for each diet, before and after immunization (V2), respectively, c diet the exponent applied to BW for each diet, BW age = 112 the BW at 112 d of age, and b pig the intercept of the relationship for each pig (so that cumulative intake of experimental diets equals zero at the start of the experiment i.
e. at 84 days of age). The parameters of the model were evaluated on the cumulative intakes using the NLIN procedure of SAS (PROC NLIN, SAS Inst. , Cary NC, USA) to avoid threshold effects caused by the way feed intake was measured (continuous access to the feeder without restriction during the few hours preceding measurement). The hypothesis for a single c diet exponent applied to BW for all diets was tested for, ME and NE intake using the extra sum of squares reduction test  [21]. As this test was never signi cant (P > 0. 10), a single exponent (1. 43) was considered for further statistical analyses to test the effect of diet and period (P1-before and P2-after V2) on the regression coe cients (slopes) of the relationship. Carcass trait, boar taint compounds, and testicular weight in Exp.
2 were analyzed using a xed-effects model of diet, treatment group, litter within slaughter batch, and slaughter batch. Measurements of morphology and mitosis cell count of small and large intestinal segments in Exp. 2 were evaluated by including the xed effects of a dietary group within the intestinal part and the random effect of the pig. The individual pig was considered as the experimental unit for all data analysis. The least-squares means were compared using the Tukey test with statistical signi cance based on P < 0. 05.
Track Costs and Benefits (Step 7) All our RFs are delivering to this step with various approaches. HRC found that urine patches deposited on hill and upland soils generate very small quantities of nitrous oxide, with implications for carbon footprinting  (Marsden et al. , 2018). UCD-LTGP is investigating the impact on above-and below-ground biodiversity, water quality, meat quality, economic, and other non-market benefits of sustainable grazing systems. ESL has demonstrated that croplivestock and crop-livestock-forest integrated systems deliver less nitrous oxide into the atmosphere as compared with conventional crop practices  (Sato et al. , 2019). The NWFP is applying Life Cycle Assessment (LCA) approaches to compare its production systems  (McAuliffe et al. , 2018) , while INIA-PAP is collating a database to apply LCA to its four crop-livestock systems.
Acknowledgments This work was funded by several sources varying with the RF. ESL:  PECUS  project (Grant number  02. 12. 02. 008. 00. 02 ). HAUF:  School of Sustainable Food and Farming. HRC: Department for Environment, Food & Rural Affairs (DEFRA)  through the  Sustainable Intensification Platform (SIP) ,  Integrated Farm Management  ( LM0201 ). INRAE-SLP:  National Research Institute for Agriculture, Food  and the  Environment (INRAE)  internal fund and  Nouvelle-Aquitaine region grant. NWFP: Soil to Nutrition Institute Strategic Programme  (grant number  BBS/E/C/000I0320 ) and The  North Wyke Farm Platform National Capability  (grant number  BBS/ E/C/ 000J0100 ) funded by the  UK Biotechnology and Biological Sciences Research Council (BBSRC). SRUC: The  Global Security's 'Resilience of the UK Food System Program ', supported by the  BBSRC , the  Economic and Social Research Council , the  Natural Environment Research Council , and the  Scottish Government.
This clone has been further weekly passaged in EMJH, at 30˚C, with agitation. Its virulence was assessed every 5 weeks in young guinea pigs by intraperitoneal infection with 2×10 8 bacteria in PBS. The virulence was assessed by death/critical end points reached within one week. Unexpectedly, this strain retained virulence for 2 years and then lost its ability to kill guinea pigs at the 104 th weekly passage, which was confirmed by subsequent passages. This 2 year-passaged isolate (Cl3 p104) was thereafter designated Verdun AV. Whole genomic sequence data from the Craig Venter Institute are available for both strains (Verdun Cl3, low passage (LP) Genome ID: 1193019.
Leptospiral load in kidneys The presence of leptospires was determined in kidneys by quantitative real-time DNA PCR (qPCR). Total DNA was purified from approximately 25 mg of frozen tissue after mechanical disruption and using QiAamp DNA purification kit (Qiagen). The qPCR reaction was calibrated using a known number of heat-killed L. interrogans. DNA concentration was adjusted to around 200 ng in the qPCR reaction and normalized using the nidogen gene (encoding a protein of the glomerular basement membrane), as a calibrator of the cortex region of the kidney, with serial dilutions of known amounts of DNA. Using Primer Express 3 software, primers were designed for the unique lpxA gene of L. interrogans Fiocruz strain  [56]  to specifically detect pathogenic Leptospira spp (Forward (Fw): 5 0 -TTTTGCGTTTATTTCGGGACTT-3 0 ; Reverse primer (Rv): 5 0 -CAACCATTGAGTAATCTCCGACAA-3 0 ; Probe: 5 0 -TGCTGTACAT CAGTTTTG -3 0 ).