dataesr/scientific-paragraphs-categorization huggingface dataset:
Funding: This research received no external private funding. Acknowledgments: This work was supported by  Labex ARCANE  ( ANR-11-LABX-0003-01 ) and  Institut de Chimie Moléculaire de Grenoble  ( FR 2607 ) and the  Glyco@Alps program  ( ANR-15-IDEX-02 ). A. F. -F. acknowledges the support obtained from the  Instituto de Salud Carlos III (ISCIII)  through its research grants ( JR18/00014 ). X. G. -O. acknowledges the financial support of the  IDIS (Health Research Institute of Santiago de Compostela)  (predoctoral research fellowships).
Funding This work was supported by  Higher Education Commission of Pakistan (HEC)  grant and  National Research Foundation of Korea (NRF)  grant funded by the  Korean government (MSIP)  ( NRF-2018R1D1A1B07042969 ). The funding agencies have no role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.
C-FÁ Á ÁCQ Q QO and related interactions The occurrence of orthogonal C-FÁ Á ÁCQO arrangements was discovered during seminal studies involving a fluorine scan of thrombin inhibitors. 94 The subsequent crystallographic  database analysis pointed out the wider importance of this type of interaction, which was also identified for C-O(H)Á Á ÁCQO. 95 he shorter the C-FÁ Á ÁCQO contact, the more the C-F bond preferred to be positioned directly over the carbonyl carbon close to the carbonyl pseudotrigonal axis. Originally suggested to be a dipole interaction, other types such as np* and p-hole interactions have also been proposed,  96  but will herein be referred to as a dipolar interaction. The C-FÁ Á ÁCQO interaction is weakly stabilizing and amounts to ca. 1 kJ mol À1. 97 While C-H for C-F substitution in small bioactive molecules usually leads to affinity increases, it must be emphasized that other factors (for example, increase in lipophilicity) may also contribute as well.
17, 98 o the best of our knowledge, a direct comparison of C-O(H)Á Á ÁCQO and C-FÁ Á ÁCQO interactions is not available yet. However, examples of the latter contacts in protein X-ray structures bound to fluorinated sugar derivatives have been described. For example (Fig. 18 ), the crystal structure of the bacterial heptosyltransferase WaaC in complex with a competitive inhibitor, ADP-2F-heptose 4. 15, displays a clear C-FÁ Á ÁCQO interaction involving the Gly263/Thr262 linkage (d = 2. 95 Å, FÁ Á ÁCQO 100. 61). 99, 100 Fig. 16  Comparison of CHF and CF 2 -motifs present in maltose fluorides 3. 18 (left) and 3. 19 (right) in complex with GlgE1 (PDB codes 4CN4 and 4U2Z). 63, 64 n interesting case arises for CHOH to CF 2 replacement, which formally includes a C-H to C-F modification. This substitution was shown to allow for the establishment of an extra dipolar interaction.
Acknowledgements B. L. thanks the  EPSRC  ( EP/P019943/1 ) for funding. L. U. acknowledges funding from the postdoctoral fellowship from the  Human Frontier Science Program Organization (HFSP)  Grant No. LT000747/2018-C. N. C. R. acknowledges funding from  Agencia Estatal de Investigacion (Spain)  Grant No. CTQ2017-90039-R  and  RTC-2017-6126-1  and the  Maria de Maeztu Units of Excellence Program. MDM-2017-0720. The group at Bilbao thank the  Agencia Estatal de Investigacion of Spain  (Grant  RTI2018-094751-B-C21 ), the  European Research Council  (RECGLYCANMR,  ERC AdG 788143 ), and the  Severo Ochoa Excellence Accreditation   SEV-2016-0644. SV acknowledges funding by  FRS-FNRS  (PDR grant number  T. 0102. 18 ).
X-ray tomography Tablets were scanned using a lab-based system at PLACAMAT (UMS 3626, Pessac, France). The facility used was a GE VTomex-s with a xs-180-nf transmission source and a diamond target. The scan parameters (voltage and intensity) were adapted for each sample. The 1800 projections for a 360° rotation were recorded using a binning factor of 1 and an exposure time of 1 second (total scanning time of two hours). The final voxel size was about 2. 5µm for all the samples. Tomographic reconstructions were performed using phoenix-datos-x2 software with default parameters. Following image treatments were performed using the software Avizo V9 (Thermo Fisher Scientific, Waltham, USA). A cube of about 1. 5x1. 5x1. 5 mm 3 was extracted from the data and submitted to further analyses. Details about the analyses will be given in the result part of the article.
Afterwards, automatic procedures of the Avizo software were used to analyze the obtained pores in terms of size. First a complete 3D analysis was intended. Nevertheless, analysis showed a large connectivity of the pore structure (i. e. more of 60% of the pores was considered to be one single pore) and this did not make it possible to isolate easily the different pores in the structure. So instead of a real 3D analysis, a 2D+1 analysis was performed (i. e. a 2D analysis of images positioned along the third direction). For each slice of the XµcT results (each analysis contained approximately 600 slices), a 2D analysis of the pores was performed. For each pore an equivalent diameter was calculated which corresponds to the diameter of the disc that would have the same surface as the pore. This diameter was taken as the characteristic size of the pores.
The French-style organization in the field of rare diseases allows a close contact between reference centres and regional pharmacovigilance centres thanks to their implementation within the French university hospital. This collaboration leads to highlight more and more drug-induced rare diseases. Through several historical examples (eosinophilia-myalgia syndrome due to L-tryptophan, type 1 narcolepsy with H1N1 pandemic influenza vaccine, capillary leak syndrome, acquired von Willebrand syndrome), it remains clear that pharmacovigilance is the cornerstone of the alert system. Clinicians from the rare disease reference centres can easily report adverse drug reactions (ADRs) to pharmacologists from their regional pharmacovigilance centre. Through experience, collaboration between countries, large database, and sometimes pharmacoepidemiological studies, an alert can then be raised.
By its implementation through the public hospital, pharmacovigilance centres have privileged relationship with medical excellence units such as rare diseases care and research units  [2]. Thanks to the pharmacovigilance clinician's expertise and their large and detailed fulfilled database, several drug-induced rare diseases had also been highlighted such as pulmonary arterial hypertension associated with protein kinase inhibitors  [7, 8]. Detecting, understanding and preventing are the three key words of this original and unique organization. Due to their specialized and advanced expertise (reflection on pharmacological mechanisms in front of unexpected ADRs, accurate reading of literature, management of specific studies and national medications follow-ups), pharmacologists are able to detect early warning signals and launch alerts to raise clinicians' awareness.
A disproportionality analysis highlighted an increased risk of capillary leak syndrome with 52 drugs, which was a new adverse drug effect for32 drugs (not yet published nor listed)  [38]. This study underlines the importance of notification to the regional pharmacovigilance centres, especially in drug-induced rare diseases. All these data contribute to feed the international pharmacovigilance database allowing international pharmacoepidemiolgic studies. Indeed, with only a few French cases, specific analysis can then be performed on the international database to highlight an association and raise an alert.
Acknowledgments: We acknowledge the contribution of the PLATIM platform of  SFR Biosciences Gerland-Lyon Sud  ( UMS344/US8 ) and the Cell and  Tissue Bank  ( Edouard Herriot Hospital ) for providing tissue samples following ethical and safety guidelines according to French regulation donors (Declaration no. DC-2008-162 ). This article summarizes work from a large number of published papers; however, due to space limitations we have not been unable to include all relevant publications and we apologize to those authors whose relevant work has not been included in this review article.
Similar data were obtained with both 1 and 0. 75 mg/mL of DSC hydroalcoholic extract. However, for cells treated with 0. 5 and 0. 2 mg/mL, there was only 20% of cytotoxicity compared to control cells. Concerning DSS-based experiments, ethanolic and hydroalcoholic extracts did not show any antiproliferative activity after either 24 or 48 h treatment. By contrast, the aqueous extract exhibited a very high cytotoxicity. At 0. 5 mg/mL, almost 90% cytotoxicity was observed after 24 h (Figure  1c ). As for DSC, this effect was further enhanced after 48 h treatment; DSS at 0. 2 mg/mL became cytotoxic with only 22% of viable cells; for higher concentrations, only 4% of live cells were left (Figure  1d ). As observed for DSC, cell treatment with 0. 1 and 0. 05 mg/mL of DSS did not result in any significant effect on the cell viability.
e. , PPARα, PPARγ, PXR, CAR, LXRα, LXRβ, FXR, for endpoints such as median effective concentration (EC50), and inhibitory affinity constant (K i ) for defined applicability domains (Table  S4 ). These include local models for CAR activity with a limited set of chemicals (e. g. ,  [25] ) to large initiatives using Tox21 HTS data for FXR  [26]  and methodologies spanning from combining molecular docking and pharmacophore filtering to identify agonists of PPARγ  [27]  to classification models identifying chemicals activating and antagonizing PXR  [28]. The growing number of 3D crystal structures of protein targets in complex with ligands provides a wealth of structural information that can be used to predict their interactions with EDCs using docking and scoring procedures. GOLIATH uses and further develops the online prediction tool called EDMon (Endocrine Disruptor Monitoring) dedicated to ligand screening of nuclear receptors which relies upon known crystal structures or models and the availability of large experimental ligand affinity datasets.
Rodent Studies GOLIATH will examine existing data generated from animal studies performed with the selected MDCs, and utilize this information to propose relevant tissues and endpoints where the current in vivo battery of test guidelines could be augmented. Note that though no new in vivo studies will be conducted within this project, partners within the GOLIATH project will team up with other partners within and outside the EURION cluster who are performing rodent studies to enable translational and cross-species comparative analyses.
New PFOA data from sampled adolescents, is expected to become available within the coming year, as part of the HBM4EU project  [105]. The PIAMA cohort will be enriched with untargeted high-resolution mass spectrometry data (exposome scan) to screen and quantify the MDCs and hundreds of other environmental chemicals in addition to endogenous metabolites  [106]. We will investigate changes in anthropometric measures (BMI, waist circumference, waist-to-height ratio), concentrations of lipids (HDL-cholesterol, triglycerides), levels of leptin and insulin, and changes in -omics readouts in relation to the concentrations of the chemicals. The possible mediating effects of the molecular markers and pathways in the exposure-outcome associations will be explored. Findings will be compared with data collected from cellular, zebrafish, and (existing) in vivo models.
Resulting sub-networks will be stored in a newly created database (alongside the international repositories for each omic data, e. g. , MetaboLights  [110]  for metabolomic data, ArrayExpress  [111]  for transcriptomics) and an online visual and interactive web interface will be developed to access these metabolic MoAs and to allow scientists to input their data to perform similar computations. This open platform will be built as an extension of the MetExplore  [112]  web server developed within the consortium.
Acknowledgments: All partners acknowledge the contribution of their institutes for additional financial support. We would also like to acknowledge the following additional members of the  GOLIATH consortium: Utrecht University , The Netherlands:  Anran Cai ,  Marjo den Broeder ,  Virissa Lenters ,  Roel Vermeulen ;  INRAE France :  Sandrine Bruel ,  Nicolas Cabaton ,  Anne Hillenweck ,  Louisa Mediouni ,  Elodie Person ,  Nathalie Poupin ,  Clément Frainay ,  Maxime Delmas ; INSERM France:  Anne Corlu ,  Vanessa Delfosse ,  Clementine Garoche ,  Marina Grimaldi ,  Jakub Gruszczyk ,  Julie Massart ,  Jean-Luc Pons ,  Lucia Toporova ,  Gilles Labesse ;  Karolinska Institutet , Sweden:  Astrud Tuck ;  Universitas Miguel Hernandez, Spain: Reinaldo Sousa dos Santos; ANSES, France: Christophe Rousselle; VITO, Belgium: Eva Govarts; Greet Schoeters; Brunel University London, UK: Andreas Kortenkamp; University of Cambridge, UK: Susana Palma; University of California, Irvine, USA: Angelica Amorim Amato, Xiaomin Ren; Biopredic International , France:  Ruoya Li ;  Umeå University, Sweden :  Maria Sapounidou  ( UMU ).
ACKNOWLEDGEMENTS This document would not have been possible without the contribution of Drs (in alphabetical order)  Filipe Espinheira ,  Michael Day ,  Marilyn Dunn ,  Walt Ingwersen ,  Roberta Portela ,  Hélène Ruel , the  Theriogenology service of the École nationale vétérinaire d'Alfort  and the  WSAVA Global Pain Council. This WSAVA List of Essential Medicines for Cats and Dogs has been published as submitted to JSAP and has not gone through the usual full peer-review process.
BACKGROUND Data on epidemiology of drug hypersensitivities (DH) is retrieved from specific registrars, electronic health records of health care systems, pharmacovigilance databases, and specific allergy work-upcentered databases. The Drug Allergy and Hypersensitivity Database (DAHD) of the Allergy Unit in Montpellier, France has been questioned several times throughout the years, to provide answers to specific questions in drug allergy epidemiology.
Search Strategy MEDLINE (Via PubMed) databases were used to search for potentially eligible articles, from inception until June 2020, in English and French. Original research papers and reviews were searched using combinations of the grouped search terms: ("Spondylitis, Ankylosing" [Mesh] OR ankylosis OR Spondylarthritis OR Spondylarthropathies OR "Spondylarthritis" [Mesh] OR "Spondylarthritides" OR "Spinal Arthritis" OR "Spinal Arthritides" OR "Arthritis, Spinal" OR "Spondyloarthritis" OR "Arthritis, Rheumatoid" [Mesh] OR "rheumatoid arthritis" OR "rheumatoid" OR "Caplan Syndrome" OR "Felty Syndrome" OR "Rheumatoid Nodule" OR "Rheumatoid Vasculitis" OR "Arthritis, Psoriatic" [Mesh] OR "Psoriasis" OR "Arthritic Psoriasis" OR "Psoriatic Arthritis" OR "Psoriasis Arthropathica" OR "Psoriatic Arthropathy" OR "Arthropathies, Psoriatic" OR "Arthropathy, Psoriatic" OR "Psoriatic Arthropathies") AND ("Spices" [Mesh] OR "Spice" OR "Spices" OR "Garlic" [Mesh] OR "Allium" [Mesh] OR "Allium sativum" OR "garlic" OR "Curcuma" [Mesh] AND "Curcumas" OR "Tumeric" OR "Tumerics" OR "Turmeric" OR "Turmerics" OR "Curcuma zedoaria" OR "Curcuma zedoaries" OR "zedoaria, Curcuma" OR "Zedoary zedoaria" OR "Zedoary zedoaries" OR "zedoaria, Zedoary" OR "Curcuma longa" OR "Curcuma longas" OR "longa, Curcuma" OR "Ginger" [Mesh] OR "Gingers" OR "Zingiber officinale" OR "Zingiber officinales" OR "officinales Zingiber" OR "Cinnamomum zeylanicum" [Mesh] OR "Cinnamomum verum" OR "Cinnamon" OR "Cinnamons" OR "Cinnamomum" [Mesh] OR "Cinnamomums" OR "Crocus" [Mesh] OR "Saffron" OR "Saffrons" OR "Crocus sativus" OR "Saffron Crocus" OR "Crocus, Saffron" OR "Iridaceae" [Mesh]).
Moreover, the six studies were done in only two countries: India and Iran. There was no study in Caucasian or African populations. Furthermore, daily saffron supplementation may not be affordable for every patient as saffron is a very rare and expensive spice. Lastly, a meta-analysis of findings could not be conducted due to the small number of studies per spice (one or two). No ongoing clinical trial to assess the impact of spice supplementation on RA activity is registered at clinicaltrials. gov. Thus, no supplementary data will be provided in the near future. In summary, according to the available evidence, garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias in these studies is difficult to assess and data are too limited to recommend them in daily practice.
Analysis of Raman Spectra For each storage condition, spectra from each depth within each cryo-section were pooled and analyzed using the software Unscrambler ® v. 11. 0 (CAMO Software AS, Oslo, Norway). For each set of spectra from fresh and frozen RHE, following a linear baseline correction, unit vector normalization was applied to remove multiplicative effects usually found in heterogeneous biological samples and arising from differences in the focus positions at which the spectra were acquired  [31, 32]. Principal components analysis (PCA) was performed on the mean-centered data using the Singular Value Decomposition (SVD) algorithm. In PCA, a data matrix X composed of n rows of spectra x p wavenumbers is decomposed in an unsupervised manner into the data structure TP T encompassing the major variation within the original data set, and noise or residuals E  [33] : X = TP T + E (1) The matrix TP T represents the original data X dimensionally reduced along independent principal components (PCs).
HPLC Analysis HPLC was performed to quantify the concentration of resorcinol in the time-dependent permeation and mass balance samples. The HPLC system Ultimate 3000 (Thermo Fisher Scientific, Voisins-le-Bretonneux, France) consisted of a UHPLC pump; an auto-injector; a diode array detector and an InterchimKromasil C18 column (4. 6 × 150 mm, 5 µm). The detection wavelength for resorcinol was 275 nm. The temperature of the column and the auto-injector was set to 25 and 15 • C, respectively. The mobile phase used in isocratic mode was methanol 25%: water 75% (v/v) + 10 mM of phosphoric acid. A flow rate of 1 mL/min was used. The injection volume was 10 µL. The duration of the analysis of each sample was 6 min. The software used was Chromeleon 7. 1 (Thermo Fisher Scientific, chromatography data system software, Voisins-le-Bretonneux, France).
Regression of Equation (  8 ) against the linear part of the experimental cumulative amount time profiles obtained from Equation (  9 ) yields J SS , the lag time t lag and the permeability coefficient K P = J SS /C D. Kinetic and mass balance results were analyzed with one-way analysis of variance (ANOVA) for multiple groups. Tukey's test was performed as a follow-up test to the multiple comparisons. The significance level was set at p = 0. 05. Statistical analyses were conducted in GraphPad Prism v. 8 (GraphPad Software Inc. , San Diego, CA, USA).
's data of EpiSkin™ RHE  [22]. Pharmaceutics 2020, 12, x FOR PEER REVIEW 7 of 19 Kinetic and mass balance results were analyzed with one-way analysis of variance (ANOVA) for multiple groups. Tukey's test was performed as a follow-up test to the multiple comparisons. The significance level was set at p = 0. 05. Statistical analyses were conducted in GraphPad Prism v. 8 (GraphPad Software Inc. , San Diego, CA, USA).
Effects of storage conditions on resorcinol intensities and on the SC barrier function of the RHE are corroborated by the time-dependent permeation data (Figure  7 ) and associated mass balances (Table  4 ). The three-to six-fold increase in the cumulative amount of resorcinol permeated through the frozen RHEs compared to the fresh RHE is in qualitative agreement with the smaller Raman intensities of resorcinol measured, i. e. , retained, within the SC of the frozen RHEs. The significantly longer mean lag time obtained from the fresh RHE cumulative amount profiles indicate that steady state is achieved later than in the frozen tissues. The significantly greater percentage of applied resorcinol recovered in the fresh RHE tissue and support membrane at the end of the time-dependent permeation experiment corroborate the higher resorcinol intensities revealed by the PCAs.
Acknowledgments: The authors thank  Françoise Debierre-Grockiego  and the team " Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses ",  Université de Tours-INRAE ,  UMR 1282 Infectiologie et Santé Publique , for access to the cryo-microtome. Y. D. acknowledges the research fellowship awarded by  Le STUDIUM Institute of Advanced Studies  and  Kamilia Kemel  for assisting with experiments and for fruitful discussions.
As expected from a previous study  [34] , geraniin severely restricted DENV-2 growth, as well as growth of the three other DENV serotypes, in Huh7. 5 at non-cytotoxic concentrations. Indeed, as observed for ZIKV, geraniin lowered DENV progeny production of the four DENV serotypes up to 3-log at 200 µg/mL. Altogether, these data demonstrate that geraniin can efficiently inhibit ZIKV and DENV infection in human cells in a dose-dependent manner and reflect its potential as a source of natural antiviral phytochemical. (F) DENV was used as a flavivirus positive control. Huh7. 5 cells were infected for 48 h with DENV at different MOI 0. 2, 2, 0. 5 and 2 for DENV 1-4 respectively with or without geraniin (200 µg/mL). The virus progeny production was titrated in C6/36 cells using a foci-forming immunodetection assay.
phillyreifolius and geraniin, respectively (Table  2 ). Any striking signs of stress, suffering, feeding behavior, and abnormal behavior were carefully checked several times a day for a period of 5 days. As shown in Table  2 , the injection of P. phillyreifolius and geraniin did not impact fish behavior (feeding and locomotion), and no sign of stress was reported (Table  2 ). Moreover, the P. phillyreifolius and geraniin treatments resulted in 100% fish survival, similar to the control injection with PBS (Table  2 ). Taken together, these data suggest that these doses do not exhibit acute toxic effects.
63 ± 1. 15%. Dry extract was stored in a freezer prior to analysis. The component analysis of extract was performed on an UPLC system equipped with a photodiode array (PDA) detector (Waters, Milford, MA, USA) according to the procedure previously described by  [32]. The separation was carried out on Acquity BEH, C18 column (100 mm × 2. 1 mm, 1. 7 µm) at a column temperature of 40 • C. The mobile phase consisted of solvents 0. 1% formic acid in ultrapure water (A) and 100% acetonitrile (B) with a linear gradient programmed as follows: 0. 0-14 min, 5% B; 15-17 min, 100% B; 18 min, 5% B. The flow rate was 0. 4 mL/min and the injection volume 1 µL. The UPLC system was coupled to quadrupole-time of flight mass spectrometer (Q-TOF) equipped with an electrospray ionization probe and controlled by HyStar software (Bruker Daltonic, Bremen, Germany).
MS data were recorded in ESI negative ionization mode over a mass range from m/z 80 to 1200, the capillary voltage was maintained at +4000 V. The peaks were identified by comparing their retention times and parent ions with external standards, references, and commercial databases. The quantification of geraniin content was performed using Acquity UPLCTM H-Class equipped with Xevo TQ-S tandem quadrupole mass spectrometer (Waters, Milford, MA) as reported elsewhere  [32]. Chromatographic separation was performed using the same column and solvents as described above with a linear gradient programmed as: 0. 0-7 min, 5% B; 8-9 min, 50,7% B; 10-11 min, 100% B; 12-20 min, 5% B. The flow rate was 0. 4 mL/min, and the sample injection volume was 5 µL. MS detection was achieved in the single-ion-monitoring (SIM) mode.