dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical analyses Normality and equal variance of data where checked using Shapiro-Wilk test and Brown-Forsythe test, respectively. When both criteria were respected, a one-way Anova followed by a post hoc test (Holm-Sidak method) was applied to evaluate the effect of the different herbal treatments; otherwise, a Kruskal-Wallis one-way Anova on Ranks was used. These analyses were used to study the effect of the different herbal treatments on blood parameters between the last day of feeding trial (day 28, before infection) and 1 day after A. hydrophila infection. Comparison before infection and after infection within each treatment group was carried out using a t-test. Mortalities resulting from the experimental infection were compared with Chi square followed by a Kaplan-Meier survival analysis and post hoc analysis using Holm-Sidak method.
Bile canaliculi area quantification Bile canaliculi (BC) area quantification was based on phase-contrast images. After capturing of images, BC areas were determined from 9 zones per condition counting around 2500 objects in 3 independent experiments using ImageJ 1. 48 software after different times of exposure. Bright objects corresponding to BC were segmented by adjusting the shape and area parameters to exclude noncorresponding objects  (Sharanek et al. , 2016).
Taurocholic acid uptake HepaRG cells were treated with cytokines or ATBs separately or simultaneously for 24 h and then washed with a standard buffer and incubated with [ 3 H]-TCA for 30 min in presence and absence of Na+, to evaluate Na+-dependent taurocholic cotransporting polypeptide (NTCP) activity. After 30 min incubation, cells were washed twice with phosphate buffered saline and lysed with 0. 1N NaOH. Accumulation of radiolabeled substrate was determined through scintillation counting. Taurocholate accumulation values in presence of sodium minus accumulation values in absence of sodium represented NTCP activity  (Antherieu et al. , 2013). Data are the mean ± SEM of 3 independent experiments. Results are expressed relative to the.
Acknowledgments This work was partly supported by the  European Community  through the  Innovative Medicines Initiative Joint Undertaking MIP-DILI project  [grant agreement number  115336 ], resources of which are composed of financial contribution from the  European Union 's  Seventh Framework Programme  [ FP7/20072013 ] and EFPIA companies' in kind contribution. Ahmad Sharanek  and  Audrey Burban  were financially supported by the  MIP-DILI project. Nadia Ciriaci  was supported by a shortterm fellowship from the  National Council of Scientific and Technical Research (CONICET)  and  National University of Rosario. Permanent address:  Institute of Experimental Physiology (IFISE) ,  CONICET ,  Rosario ,  Argentina. We are grateful to  Dr Rémy Le Guevel  from the ImPACcell platform for image acquisition.
Interactions between GSTs and wood extracts To set up the experimental design, heartwoods of 17 species from French Guiana tropical forest have been selected (Table  1 ). Data obtained the heartwoods from Andira coriacea, Bagassa guianensis, Dicorynia guianensis, Hymenaea courbaril, Peltogyne venosa, Sextonia rubra, and Tabebuia serratifolia have been previously published  (Perrot et al. , 2018). Heartwoods from Abarema jupunba, Bocoa prouacensis, Hirtella bicornis, Oxandra asbeckii, Parkia nitida, Parkia pendula, Pouteria decorticans, Protium gallicum, Swartzia canescens, Vouacapoua americana were from commercial origin (Degrad Saramaca's sawmill, Kourou, French Guiana) or harvested as described in  Lehnenbach et al. , 2019. All these woods belong to the DEGRAD database  (Beauchène, 2012).
The DEGRAD database contains wood density and wood durability data for more than 300 tree species from French Guiana tree species Among the 17 chosen woods, four are classified as very durable (x<10%, x being the relative mass loss obtained during the soil tests), five as durable (10%<x<25%), five moderately durable (25%<x<45%) and three non-durable (x>45%) (Table  1 ). From the 17 selected species, molecules from corresponding heartwoods have been sequentially extracted using four solvents exhibiting different polarities (dichloromethane, acetone, toluene/ethanol, and water). From this step we obtained a collection of 68 wood extracts. On the other hand, 6 GSTs belonging to the omega class from Trametes versicolor (TvGSTOs), have been used to characterize the wood extracts. Previously, those TvGSTOs have been shown to be able to bind wood polyphenolic compounds  (Schwartz et al.
GSTs and wood durability Wood durability is usually estimated from long term soil bed tests  (Meyer et al. , 2014; XP CEN/TS 15083-2. 2006. ). To constitute the DEGRAD database, soil tests have been performed incubating wood blocks in French Guiana soils in 2010/2012 in controlled laboratory conditions as mentioned in  Amusant et al. (2014). Mass losses (%) have been measured after 6 incubation months. Data from DEGRAD database were used to quantify wood durability of the seventeen species used in this experiment. 68% of the variability (p<0. 006) of the measured mass losses could be explained by a model (linear regression) set up from the four "GST reactivity variables" as shown in Table  2  (%mass loss = 19 + 6. 6 ΣΔTdA -1. 6 ΣΔTdD -6. 3 ΣΔTdTE -4. 5 ΣΔTdW ; R 2 = 0. 679, p < 0. 006). This significant correlation supported the hypothesis that "GST reactivity" could reflect at least partially the wood durability of the considered species.
GST reactivity and wood density Wood durability is known to be inversely correlated to wood density (WD). Using more than 300 species of the DEGRAD database, significant correlation between wood density (12% of humidity) and durability (mass losses (%) obtained from soil tests) has indeed been previously observed (R 2 = 0. 43)  (Chave et al. , 2009 ; Larjavaara et al. 2010). We postulated that "GST reactivity" and WD should be link to explain the durability of the tested species. From the same data set (17 heartwoods; Table  1 ), WD and "GST reactivity" are not significantly correlated (p>0. 05). In contrast, as expected, WD could be an was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. indicator of wood durability estimated by soil bed tests (r=-0.
min - 1. The denaturation temperature (Td), which corresponds to the temperature where the protein is 50% unfolded, was determined using the first derivative of the obtained data in the presence or in the absence of potential ligands. As reference, experiments were conducted by adding DMSO only, allowing the determination of Td ref. The corresponding values are the average of three technical repetitions, standard deviation remaining in all cases below 10%. Then, the difference between the denaturation temperature of the protein incubated with wood extracts and with DMSO only (Td ref) were calculated in order to obtain the thermal shift (ΔTd). Absolute values of ∆Td were then reduced centred. Solvent : A: Acetone; D: Dichloromethane; TE: Toluene/Ethanol; W: Water.
Acknowledgements This work was supported by a grant overseen by the  French National Research Agency (ANR)  as part of the  "Investissements d'Avenir"program  ( ANR-11-LABX-0002-01 ,  Lab of Excellence ARBRE)  and the  Region Lorraine Research Council. We thank  Solène Telliez  and  Fanny Saiag  for technical assistance.
59 3. 45 5. 70 1. 13 Dicornia guianensis 17. 6 0. 78 D -1. 89 1. 96 -0. 50 -1. 51 Hirtella bicornis 23. 8 0. 96 D -2. 31 -2. 46 -3. 95 0. 30 Hymenaea courbaril 48. 3 0. 89 ND 5. 55 5. 18 1. 79 -1. 01 Oxandra asbeckii 27. 4 1. 03 MD -3. 47 -2. 50 -3. 17 -2. 67 Parkia nitida 62. 6 0. 33 ND -2. 69 3. 59 -4. 62 -2. 73 Parkia pendula 44. 4 0. 49 MD 4. 58 0. 32 0. 22 -1. 58 Peltogyne venosa 25. 7 0. 88 MD -0. 31 -1. 26 -0. 54 -1. 89 Pouteria decorticans 9. 7 0. 87 VD 1. 35 -3. 75 4. 01 0. 65 Protium gallicum 28. 7 0. 75 MD -3. 50 -2. 45 -2. 61 -2. 14 Sextonia rubra 18 0. 68 D -2. 48 1. 19 -4. 12 0. 31 Swartzia canescens 37. 1 1. 00 MD -2. 20 -3. 25 -3. 85 -0. 88 Tabebuia capitata 6. 8 1. 20 VD -1. 39 5. 80 -1. 94 -2. 45 Vouacapoua americana 9 0. 90 VD 1. 20 4. 51 1. 72 0. 48 * Values extracted from the DEGRAD database ΣΔTd A: GST reactivity obtained with the acetonic extract of the considered wood species Variables %mass loss Wood density ΣΔTd A ΣΔTdD ΣΔTd TE ΣΔTd W %mass loss 1 -0,657 -0,144 -0,129 -0,464 -0,398 (p <0.
Source operating conditions were as follows: 3 kV spray voltage for negative mode; 320°C heated capillary temperature; 400°C auxiliary gas temperature; sheath, sweep, and auxiliary gas (nitrogen) flow rate 60, 17. 5, and 3. 5 arbitrary units, respectively; and collision cell voltage between 20 and 50 eV. Full scan data were obtained at a resolution of 35,000 whereas MS 2 data were obtained at a resolution of 17,500. Data were processed using Xcalibur software (Thermo Fisher Scientific Inc. , MA, USA). The constituents of the R. rosea HRE were identified according to their retention times and mass spectral data and by comparison with authentic standards, if available, or otherwise with published data.
| HPTLC analysis of R. rosea HRE Standards were diluted in methanol at a concentration of 0. 5 mg/ ml for rosavin and 0. 1 mg/ml for salidroside (Sigma Aldrich, Saint Louis, USA). One mL of the R. rosea HRE (without added glycerol) was diluted in 3 ml of a mixture of 50% ethanol and water (50/50: v/v). The resultant solution was shaken and centrifuged for 3 min at 6,600 g. The supernatant solution was transferred into individual vials and then analyzed by HPTLC. HPTLC analysis was performed on 200 × 100 mm silica gel 60 F 254 HPTLC glass plates (Merck, Darmstadt, Germany), using a Camag HPTLC system (Muttenz, Switzerland) equipped with an Automatic TLC Sampler (ATS 4), an Automatic Developing Chamber ADC2 with humidity control, a TLC Visualizer, WinCATS software and for derivatization, a Chromatogram Immersion Device III, and a TLC Plate Heater III.
| Assessment of RNA expression using Fluidigm microfluidic arrays One microgram of total RNA was obtained from each brain area as described in Dinel et al. (Dinel, Andre, et al. , 2014)   control specific amplification for each primer. Then, the raw data of the qPCR were analyzed using GenEx software (MultiD analyses AB, Freising, Germany) in order to choose the best reference gene for normalizing mRNA expression and to measure the relative expression of each of the 93 genes analyzed in the group receiving the HRE and the control group. GAPDH was found to be the best reference gene in this experiment and was therefore used for normalization of gene expression.
| Bivariate statistical analysis All data were expressed as the mean value ± SEM (standard error of the mean). A p-value of 0. 05 was considered as significant. Data were analyzed using a one-way ANOVA (one factor: supplementation) or a two-way ANOVA with supplementation (HRE, control), and stress (stress; no stress) as between factors followed by a Bonferroni post hoc analysis when interaction was significant (GraphPad software, La Jolla, US). Heatmaps were obtained using the Permut Matrix program  (Caraux & Pinloche, 2005).
| Principal component analysis (PCA) PCA was used to assess the gene expression pattern under stress conditions in the group receiving R. rosea HRE and the control group. The PCA is a dimension reduction technique that clusters data into principal components (PC) maximizing the variance of the data considered. These PCs are uncorrelated linear combinations of the initial variables which can be interpreted as a pattern. PCA generates factor loadings which reflect the correlation of each variable with the PC and attributes a PC score for each individual. We selected the number of components using the Cattell criterion. Statistical analyses were performed using the XLSTAT program (Addinsoft, Paris, France).
Since infusion mode has been found to be one of the best compromises as far as ground materials are used, the optimized protocol was based on infusion. Temperature decrease profiles (see Figure  S11  in Supplementary Materials) can be correctly fitted (for natural convection experiments only) using a relatively simple model that considers the nature and geometry of the recipient. This model was based on the numerical resolution of the system of differential equations corresponding to the instantaneous material and thermal balances using a Mathcad script courteously provided by  Condoret [100]. For example, 58% of the heat is evacuated via the vertical wall, and 32% by evaporation for the mug. On the other hand, when the horizontal surface is greatly increased, the evaporation contributes to more than 65% of the energy loss.
UHPLC and UHPLC-ESI-MS Analysis All samples analyzed are presented in Table  S1. A 20 mg hawthorn dry extract was dissolved in 1 mL MilliQ water, and finally strongly vortexed for 2 min. The resulting solution was diluted five times with MilliQ water, vortexed again for 2 min, and analyzed by UHPLC-DAD and UHPLC-ESI-MS. The UHPLC-DAD system consisted of a Thermo Scientific™ Dionex™ UltiMate™ 3000 BioRS equipped with a WPS-3000TBRS auto sampler, and a TCC-3000RS column compartment set at 35 • C (Thermofisher Scientific, Waltham MA, USA). The system was operated using Chromeleon 7 software. A Luna ® Omega polar C18 column (1. 6 µm, 100 × 2. 1 mm) combined with a security guard ultra-cartridge was used (Phenomenex Inc. , Torrance CA, USA). A binary solvent system was used, consisting of water/formic acid (1% , v/v) as solvent A and acetonitrile/formic acid (1% , v/v) as solvent B.
(-) ESI FT-ICR-MS Analysis All of the analyzed samples are given in Table  S1  and were studied in duplicate. Extraction of the achieved material, depending on the diverse extraction processes, was carried out by 2 mL methanol addition in vial and 5 min ultrasonic bath at room temperature. The methanolic extracts (from light to dark yellow), constituting the stock solutions, were recovered and put in 2. 5 mL vials for 2 min centrifugation at 14,000 rpm for 2 min. These solutions were then diluted 100 times in methanol. Standardized EPS Phytoprevent ® and Crataegisan ® Bioforce extracts were diluted to 0. 5% in methanol. Sample analysis was performed with a 12 T FT-ICR mass spectrometer Solarix (Bruker Daltonics) and the parameters were optimized via software FTMS-Control V2. 2. 0 (Bruker Daltonics).
Prior to acquisition, the mass spectrometer was externally calibrated with arginine clusters (10 mg/L in methanol). Hawthorn methanolic solutions were infused with a flow rate of 2 µL/min in the ESI source (Apollo II, Bruker Daltonics) used in negative-ion mode with a capillary voltage set at 3. 6 kV. The temperature and the flow rate of the drying gas were kept at 180 • C and 4 L/min, respectively, and the pressure of the nebulizer gas was 2. 2 bar. Mass spectra resulted from the accumulation of 300 scans over a m/z 122-100 range, and with a 4 megaword time-domain. The achieved mass spectra were processed in Data Analysis 5. 0 (Bruker Daltonics). An internal calibration with a list of well-known C x H y O z (fatty acids and sugars) anions was performed with mass accuracy values lower than 200 ppb.
Peak lists were generated at signal-to-noise ratio ≥4 and exported. The algorithm developed by Kanawati et al. was applied to remove signals related to satellite and magnetron peaks  [104]. Apart from the standard extracts, the samples were analyzed in duplicate, therefore, only features observed in both replicates were kept. The filtered mass lists of the different samples were finally aligned into a matrix based on their m/z values with a 0. 5 ppm tolerance. The achieved matrix was processed for assignment in an in-house software, Netcalc  [105] , with an annotation tolerance of 0. 2 ppm. Eventually, the CHO, CHOS, CHON, and CHOCl compound families were assigned. Perseus software was used to perform hierarchical cluster analysis (HCA) and to generate heatmap from the data achieved by (-) ESI FT-ICR MS analysis of the samples.
Close to 400 specific features were retrieved depending on the extraction process, plant status, or physical shape (raw or ground). These were then represented in a histogram according to their heteroatom class and the van Krevelen diagram. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were carried out by SIMCA-P 9. 0 software. Some of the achieved raw formulae were putatively assigned with compounds previously identified in the fruit, leaves, and flowers of Crataegus  [39, 40, 106]. Thus, 56 compounds were assigned and referenced, with their exact mass in the [M -H] -form in Table  S3.
For Levothyrox®, More Than 50% of Subjects Enrolled in a Large European Union Regulatory Average Bioequivalence Trial were Actually Outside the a Priori Bioequivalence Range Because of public and media concerns, and the desire of the French regulatory authorities to ensure full transparency for this major public health crisis, the BE dossier, including its raw data, have been made public: it can be down-loaded on the Agence Nationale de Sécurité du Médicament et des Produits de Santé  [18]. The dossier provided data on L-T4, hereafter named T4. The T4 concentration-time profiles of 204 healthy individuals, for both old and new formulations, were retrieved. Blood samples were taken before administration (baseline) and regularly up to 72 h post-administration. For individual subject concentration-time profiles, AUC was computed by trapezoidal methods.
Statistical analysis Descriptive statistics were used to present the global results. For comparisons between two groups, Fisher exact (for categorical data) and Mann-Whitney U (for non-Gaussian continuous or ordinal data) tests were used. For comparisons between three or more groups, Fisher exact (for categorical data) and Kruskal-Wallis (for non-Gaussian continuous or ordinal data) tests were used. For testing correlations between the use of PGx biomarkers and the number of PubMed publications or the number of drugs with prescribing guidelines for a specific PGx biomarker, nonparametric Spearman correlations were used. All of these tests were carried out using the SPSS statistical program (version 24; IBM, NY, USA). For all of the statistical tests, differences with p values ≤ 0. 05 were considered significant.
The use of original research papers for PGx education that was evident from our global survey is again in line with the 2005 recommendations  [24]. Internet databases were also very popular for PGx education, and equally so among all of the subgroups of responders. This is probably because they typically have open access, while many original research papers are still kept behind pay walls and are not accessible to all universities. This use of web resources in PGx education is also in line with the 2005 recommendations  [24]. By far the most frequently used website for PGx education was PharmGKB  [30] , which was reported by 60. 0% of all of the internet database users (Figure  5B ; Supplementary Table  1 ). The majority of the textbooks used by our survey responders were in the field of pharmacology and toxicology, and in one instance biochemistry (Supplementary Table  2 ).
Then, using the SAXS experimental data, we were able to compute low-resolution envelopes of the complexes. The degree of similarity between the X-ray structures and the in-solution envelopes was assessed by cross-correlation (CC). High CC scores were obtained for both complexes (Ec, 0. 89; Tth, 0. 9), showing a very good fit between the solution and crystal structures (Figure  3c, d ). In addition, rigid-body modeling of the monomers against the solution scattering data resulted in dimeric models adopting conformations very close to those of the X-ray structures (Figure  S4c ). These results confirm that the different conformations of the complexes observed in the X-ray structures are the same in solution and not triggered by crystal contacts. The complete COU molecule could be fitted in the electron density of both structures (Figure  2a, b ).
* S Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10. 1021/acs. jmedchem. 8b01928. Experimental section; tables for crystallographic data collection and refinement statistics, biophysical charac-terization of GyrB 43K-COU complexes and PISA analysis; figures showing biochemical and biophysical characterization of the GyrB 43K-COU complex and DNA gyrase-COU complex, analysis of the structures with regard to COU mutant strains, ab initio calculation of COU, model for the in vivo interaction of DNA gyrase with COU, and supporting biotechnological usage of COU (PDF) Molecular formula string for coumermycin A1 (CSV).
These data will be assessed for improvements in communication and shared decision-making and to see if this is reflected by improved patient and HCP reported outcomes. Gavin Giovannoni is a steering committee member for AbbVie (daclizumab trials) and Biogen Idec (BG12 and daclizumab trials), and has received honoraria for speaking from Canbex Therapeutics. He is a clinical advisor regarding the development of VSN16. He has received consultancy fees for advisory board meetings for GW Pharmaceuticals, and for speaking at the launch of Sativex in Norway. Dawn Langdon has participated in speakers bureaus for Bayer, Merck, Almirall, Excemed, Teva, Roche, Novartis, Biogen, and Sanofi; has received consultancy honoraria from Novartis, Bayer, Merck, Biogen, Teva, and Sanofi; and has received research grants from Bayer, Merck, Novartis, Biogen, all paid to her institution.
Nektaria Alexandri is a Merck KGaA employee. Jane Shanahan, Pieter Van Galen and David Yeandle have nothing to disclose. Compliance with Ethics Guidelines. This publication does not contain any clinical studies with human participants or animals performed by any of the authors. All survey responses were undertaken on a voluntary basis with acceptance of terms outlining the use of the data. All responses were received and analyzed in an aggregated and anonymous format. Data Availability. The datasets during and/ or analyzed during the current study are available from the corresponding author on reasonable request. Open Access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4. 0 International License (http://creativecommons. org/licenses/ by-nc/4.
ACKNOWLEDGEMENTS We thank the MS in the 21st Century steering group members for their participation in the development of these tools, and the respondents of the survey for their valuable contribution to the dataset. Funding. The MS in the 21st Century initiative is financially supported by  Merck KGaA, Darmstadt, Germany. The journal's  Rapid Service Fee  and  Open Access Fees  were also funded by  Merck KGaA, Darmstadt, Germany. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Editorial Assistance. Administrative support and editorial input was provided by  Cello Health Communications. Medical writing assistance was provided by  Cello Health Communications  ( Owen Webb ,  Helen Hammond , and  Rudy Sarmah ).
ATR-FTIR Spectroscopy Analysis ATR-FTIR spectra of samples and physical mixtures were recorded on a Perkin Elmer Spectrum 100 FT-IR (Perkin-Elmer, Shelton, CT, USA) in the region of 4000-650 cm -1. Data acquisition was done using spectrum software version 10. 03. 05 Perkin Elmer Corporation (Perkin-Elmer, Shelton, CT, USA).