dataesr/scientific-paragraphs-categorization huggingface dataset:
In Vitro Release Studies In vitro drug release experiments were carried out in a multi-compartment rotating cell, comprising a donor chamber separated by a cellulose membrane (cut-off = 12,000 Da) from a receiving compartment. One milliliter of the different IMQ formulations (CD complexes, IMQ-loaded NS), at the drug concentration of 1 mg/mL, was placed in the donor chamber. The receiving phase, containing saline phosphate buffer 0. 05 M (pH 5. 5), was withdrawn at regular intervals and replaced with the same amount of fresh buffer. Quantitative determination of IMQ in the receiving phase samples was carried out by the HPLC method, as described in the previous paragraph. Data were expressed as % of IMQ released over time. An IMQ suspension at the concentration of 1 mg/mL was used as control.
MTT Colorimetric Assay The viability of the fibroblasts was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide (MTT) assay (Roche, Risch, Switzerland). Fibroblasts were seeded at a density of 1 × 10 4 cells/well in a 24-well plate. After 2 h, the cells were either incubated with the indicated compounds or left untreated. Cell proliferation analysis was performed in triplicate after 24, 48, 72 and 96 h of treatment by spectrophotometric readings at 570 nm using an Eppendorf BioPhotometer (Eppendorf, Hamburg, Germany). Data are shown as the optical density or as a percentage of the average proliferation rate compared to the control/unstimulated cells or blank NS.
Also, SCs are increasingly used by vulnerable groups, such as the homeless people. Part of the problem in controlling SCs lies in their variety, their low cost, and the fact that they are undetectable by standard toxicology screening as they do not cross-react with THC commercial tests. Thus, their identification in different biological and non-biological matrices require reliable analytical methods based on chromatographic techniques coupled with mass spectrometry detection (e. g. GC-MS, GC-MS/MS and LC-MS/MS)  [6, [18] [19] [20] [21]. Even if targeted screenings are highly sensitive and specific, they remain limited by the unavailability of reference standards (RS). Consequently, it is likely that the number of reported cases is underestimated. In recent years, high resolution mass spectrometry (LC-HRMS) methods allowed seeking for SCs without a need for RS as they are based on a shared MS spectra database continuously enriched with newly marketed NPS spectra  [22].
LC-MS-MS system and conditions Chromatography was performed on Accela liquid chromatography system (Thermofisher, Les Ulis, France) composed of a CTC analytics autosampler (Thermofisher), a multi-switch column module (MayLab multiswitch 3. 0, Vienna, Austria) coupled to a quaternary eluting pump. The chromatographic separation was achieved using a porous Hypersyl Gold PFP column (100 × 2. 1 mm i. d. , particle size 1. 9 μm, ThermoFisher) preceded by a javelin TM column filter (2. 1 mm i. d. ) and maintained at 30 C°. Elution of compounds was performed by a gradient of formate buffer 2 mM in 0. 1% formic acid (A) and acetonitrile (B) starting from 30% of acetonitrile to 90% at a flow rate of 300 µL/min. The total analysis time was 14 min, including 2 min column re-equilibration. Compounds were detected by a TSQ Vantage triple-quadrupole mass spectrometer (Thermofisher) equipped with an electrospray ionization (ESI) source set in positive ionization mode.
Ion-spray voltage of +4 kV was applied. The capillary temperature was set at 350 °C. Nitrogen (Nitrox UHPLCMS 18, nitrogen generator, Domnick Hunter, Villefranche sur Saone, France) was employed as sheath and auxiliary gas at a pressure of 50 and 20 arbitrary units, respectively. The argon gas collision-induced dissociation was used with a pressure of 1. 5 mTorr. The scan time was of 2 seconds. Data were collected in selected reaction monitoring (SRM) mode, with two m/z transitions per analyte. The determination of the optimal MRM transitions and respective collision energies for both quantifier and qualifier ions were carried out by direct injections of 1 µg/mL individual CRM solutions of SCs through the mass spectrometer. Protonated molecular ions [M + H]+ were selected with a mass resolution of ±0.
5u (atomic mass unit) and fragmented with different collision energies (CE) to obtain two product ions for each parent drug. Chromatographic data acquisition was performed using Xcalibur software (v2. 2 SP1). Postanalysis processing was carried out using LCQuan software (v 2. 7. 0 SP1), ThermoFisher Scientific. MRM transitions and retention times of synthetic cannabinoids investigated in the present study are reported in Table  1.
2-50 ng/mL and exhibited satisfactory validation parameters (data not shown). Ten milligrams of the powder were weighted and diluted in 10 mL of methanol to obtain a 1 g/L solution. Three stock solutions at 1, 10 and 100 mg/L were then prepared by successive dilutions in the same solvent. Two hundred microliters of each solution were mixed with 20 µL of JWH-018-D11 (5 mg/L) and evaporated to dryness. The final residue was reconstituted in 200 µL of the mobile phase (the same used above) and 10 µL were injected. Compounds were eluted by an isocratic flow (200 µL/min) of formate buffer 2 mM in 0. 1% formic acid (A) and acetonitrile (B) (60:40) in 7 min. JWH-122 was separated by turbulent flow chromatography (TFC) using Cyclone extraction column followed by HypersilGold column (100 × 2. 1 mm i.
Acknowledgments This research was in part funded by the project EUNCL 2015, a European Union's  Horizon 2020 Research and Innovation Program  under grant agreement No  654190. This project has been funded in whole or in part with Federal funds from the  National Cancer Institute, National Institutes of Health , under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the  Department of Health and Human Services , nor does mention of trade names, commercial products, or organizations imply endorsement by the  U. S. Government. Conflict of Interest Disclosure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
0 min: 35%A/65%B, t18. 0 min: 35%A/35%B, t19. 0 min: 100% and finally isocratic conditions (100%A) for 11 min. The optimized mass spectrometric conditions are positive electrospray ionization (ESI) mode, drying gas (N2) flow rate 8. 0 L/min, drying gas temperature 325°C, nebulizer pressure 50 psi, fragmentor potential 175 V, capillary voltage 3500 V, octapole radio frequency voltage (Oct RFV) 750 V and skimmer voltage 65 V. Data acquisition and analysis were performed using MassHunter software (Agilent Technologies). A calibrating solution (G1969-85000, ES-TOF Tuning Mix) was used daily to obtain accurate mass measurements for each peak from the total ion chromatogram. The ESI-MS spectra were obtained at m/z range of 100 to 1500. Samples (SB and SC) were dissolved at 85 and 95 µg/mL, respectively, in a mixture of IPA and MeOH (1:1, v/v).
0 min: 100%B, t35. 0 min: 100%B, t36. 0 min: 80%A/20%B, t40. 0 min: 80%A/20%B. Prior to the isolation, Myrj™ S40 was dissolved at 250 mg/mL in a mixture of CHCl3 and MeOH (2:1, v/v). Detection was performed in positive ionization electrospray mode with the following source conditions: capillary voltage 3. 5 kV, cone voltage 35 V, source temperature 150°C, desolvation temperature 450°C, desolvation gas flow 900 L/h, and cone gas flow 50 L/h. Instrument control and data acquisition were performed using MassLynx SCN627 4. 1 software. Fraction collection was triggered automatically by signals from the MS detector at m/z = 1538, 1732, 1760, 1584, 1952 and 1980. The minimum intensity threshold was fixed at 200,000. For each collected fraction, methanol was evaporated by rotary evaporation (50°C) and the fractions were freeze-dried and stored at -20°C.
Acknowledgement SB SC PC PE PEG-C16 PEG-C18 1 Table  1 : Gradient elution program used for the analysis of lipids belonging to Soybean (SB) oil, Suppocire (SC) and Myrj S40 (S40) using 100% water (A), 100% methanol (B) and a mixture of isopropanol and acetonitrile in a volume ratio of 75:25 (v/v) (C). This method is referred as "QMC18" in the manuscript.
Acknowledgements Thea uthors would like to thank  Dr. Bernard Rousseau  for valuable discussions. A. P. , V. P. and D. B. are participants in the  EU Isotopics consortium. TheI SOTOPICS  project has received funding from the  European Union Horizon2020 Research and Innovation Programme  under the  Marie Sklodowska-Curie  grant agreement  675071. This work was also supported by the  MetaboHUB infrastructure  ( ANR-11-INBS-0010  grant).
These sample-to-detector distances afforded q ranges of 0. 01 < q < 0. 40 (1. 6 m) and 0. 04 < q < 2. 00 (0. 6 m) Å -1 , where q is defined as the length of the scattering vector i. e. , (4π/ λ)sin(2θ/2), where 2θ is the scattering angle. 2D SAXS patterns were recorded using a Pilatus 1 M detector with 5 s acquisition times and a 15 s delay between measurements (one measurement every 20 s). The 2D data were reduced to scattering functions I(q) versus q by radial integration using the in-house software ScatterBrain Version 2. 71. 2. 3. 2. Equilibrium Static Configuration for Measurements of Solid-State Drug Powders and Pellets. SAXS patterns of the FQ API powder, FQ granules, re-precipitated FQ API (to check for any polymorphic transformation of FQ from gastric to intestinal pH), and the pellets collected after ultracentrifugation of the digested samples were obtained by loading the samples into 1.
■ ACKNOWLEDGMENTS This work was funded by the  Bill and Melinda Gates Foundation  grant number  OPP1160404  in collaboration with  Medicines for Malaria Venture (MMV). Funding is also acknowledged from the  Australian Research Council  under the  Discovery Projects scheme   DP160102906. The SAXS experiments for this work were conducted on the SAXS/WAXS beamline of the  Australian Synchrotron , part of  ANSTO. The authors thank  Dr. Niya Bowers  for technical and historical discussions around co-administration of  OZ439  and FQ with milk.
According to the French national transparency database  [18] , 77. 5% of physicians at teaching hospitals received at least one payment or gift (including in kind) over the period 2012-2016. In 2014, 84% of doctors registered with the National College of Physicians received payments or gifts declared in the database  [19]. Medical faculty members are particularly sought-after by industry as key opinion leaders (KOL) who have a strong influence on the practices and representations of their present and future colleagues, and easy access to the media. [20] [21] [22] [23] [24]  At the institutional level, how hospitals are financed, especially research activities, introduces a conflict of interests. A growing proportion of teaching hospitals' budgets, known as MERRI credits (Missions d'enseignement, de recherche, de reference et d'innovation -teaching, research, reference and innovation missions), is linked to criteria such as citation indices for publications, or the number of patients included in clinical trials  [1].
Data collection We used several methods to obtain information on COI policies at the 32 teaching hospitals. First, we searched the website of each teaching hospital in May 2017 and November 2017 to find policies related to COI or documents interpreting policies using the French terms: « conflits d'interêts » (conflict of interests), « liens d'interêts » (competing interests), "declaration publique d'interêts" (public declaration of interest), « industrie pharmaceutique » (pharmaceutical industry), « laboratoire pharmaceutique » (pharmaceutical firm), "ethique" or "deontologie" (ethics), "visiteurs medicaux" or "visite medicale" (companies representatives), "financement" (funding), « charte » (charter), et « règlement interieur » (internal rules). The name of each policy and the latest date of adoption or the date of the policy's most recent review were recorded.
However, the registration and publication of clinical trials is not addressed by any teaching hospital. Eight French teaching hospitals were amongst the 20 sponsors internationally with the largest rate of unreported trials registered on clinicaltrials. gov, according to the Alltrials initiative  [38]. Several hospitals have set up foundations to centralize external funding of their research. However, a score of 3, reflecting a high policy standard, required the publication of amounts received from companies, and that the foundation replaces and eliminates prior funding circuits, namely ad hoc charities created and managed by the hospital departments, known as 'associations de service'. These are prone to opacity and conflicts of interests and the French General Accounting Office has recommended their elimination  [1].
This regulation allows derogations only for doctors, allowing them to carry out activities on behalf of healthcare companies (consulting, expertise, teaching). When the hospital regulation does not specify any waiver, we had to consider that any advantage or ancillary activity is indeed prohibited and grant a rating of 2 or 3 for criteria 1 and 7. However, experience and data from the public transparency database prove that this policy is not enforced  [18]. These criteria definitions shall warrant revision in future studies. Public disclosure of interests is addressed in three of the criteria: whether clinical staff working within a hospital must declare their COI (criterion 10). ; whether staff involved in procurement and managerial positions must declare COI (criteria 15 and 18). We retained the three criteria because of the different nature of these functions and because internal hospital rules often differentiate between these functions.
Statistical analysis A descriptive analysis of the studied parameters was carried out. Results were expressed as mean ± standard deviation and/or median, minimum and maximum for quantitative variable and as percentages for categorical variables. A Student T-test was performed for the comparison of the variables according to groups of interest. A subgroup analysis compared patients aged 75 years and older (n = 91) to the rest of the sample, among other subgroup analyses. Analyses were performed with Graphpad ® software version 5. 0.
Chironomids At the end of the experiment, mortality, growth and teratogenicity were assessed in chironomid larvae that were not predated by Pleurodeles. A careful sorting of the sediment allowed to count the surviving individuals which were then measured using the image-J software (total length and width of the cephalic capsule). The cephalic capsules were recovered and discolored in potassium hydroxide (15%, 95°C, 15 min), then mounted on microscope slides with quickhardening medium (Sigma). Teratogenecity was assessed by counting the number of deformities in mentum. According to Salmelin et al. [38] , only absolute deformities such as missing and extra teeth and Köhn gaps were taken into account.
Amphibians No endpoint was measured in X. laevis tadpoles that were all predated during the experiment by Pleurodeles larvae. For Pleurodeles larvae, mortality, growth and genotoxicity were studied after 10 days of exposure (n = 15 for each endpoint per microcosm). Mortality was checked daily throughout the exposure. Growth was studied by measurements of size (photo and image analysis with Image-J software) at the beginning and end of the experiment. Genotoxicity was assessed by enumeration of micronucleated erythrocytes (MNE) in blood smears after fixation (methanol 99. 9%) and staining (groat hematoxylin). The number of cells containing one or more micronuclei was counted among a total of 1000 cells.
Statistical analysis Statistical analysis was performed using Minitab 16 Statistical software. Data of growth (P. waltl and C. riparius), development and survival chironomids (growth, development and survival) as well as leaf litter degradation endpoints were analyzed using one-way ANOVA when assumptions of normality and homogeneity of variance were met. As it was not the case for genotoxicity data, non-parametric Kruskal-Wallis followed by Dunn's multiple comparison test was performed. For metagenomics analysis, data manipulations, OTUs counts, alpha diversity indexes and Unifrac Distances calculations as well as multidimensional scaling (MDS) plot were carried out using "Phyloseq" R package  [54]. Differential abundance of bacterial genera between exposed conditions compared to the control group was examined using "Deseq2" R package  [55].
Two clinical studies also bring new data that could help the understanding of the mechanism of action of baclofen. Morley et al. , using magnetic resonance spectroscopy, show that baclofen increases the concentrations of the antioxidants glutathione and N-acetyl aspartate in the brain of patients with AUD, and that higher glutathione levels predict favorable outcomes at follow-up. This supports the idea that the beneficial effects of baclofen in the treatment of AUD could be, at least in part, related to neuroprotective mechanisms (Morley et al. ). Durant et al. show that the effects of an acute administration of baclofen are very different in patients with AUD compared with healthy controls. The measured effects were growth hormone release and.
In short, identification of the components was carried out by comparing chemical shift values in the mixture spectrum with those of reference spectra compiled in two libraries devoted to triterpenes, using in-house software (Figure  1 ). The first spectral data library was constructed with spectra recorded in the laboratory while the second one was built with spectral data picked up in recent literature (spectra recorded with diluted samples). Each compound was identified by taking into account three parameters that were directly available from the computer program: (i) the number of observed signals with respect to what was expected, (ii) the difference between the chemical shift of each signal in the mixture and in the reference (∆δ), and (iii) the number of overlapping signals of carbons belonging to two components that fortuitously possess the same chemical shifts  [29, 31]  Leaves of I.
Identification of Individual Components Both extracts (hexane and dichloromethane) as well as all the fractions of CC were analyzed by 13 C-NMR, following a computerized procedure developed at the University of Corsica (see results)  [30, 32]. Neutral triterpenes and triterpene acids were identified by comparing their carbon chemical shifts with those of references compiled in the in-house library (which contains about 50 compounds bearing steroidal structures or pentacyclic structures of oleanane, ursane, or lupane families and that is continuously enriched) or literature data (about 550 compounds). Carbon chemical shifts of amyrin fatty acid esters were compared with literature data  [35, 36]. Fatty acid methyl esters were analyzed by GC (FID), GC-MS, and 13 C-NMR by comparing retention indices (RIs), mass spectra, and carbon chemical shifts with those of references compiled in the in-house libraries or literature data.
Direct 12 C/ 13 C-Exchange of Carboxylic Acids a a Ni/L1, Table  1 ; Ni/L2, NiBr 2 •dme (10 mol %), L2 (24 mol %), Mn (2 equiv), TBAB (1 equiv),  13  CO 2 (1 atm) in DMF (0. 17 M), at 60 °C; Ni/L3, NiBr 2 •diglyme (10 mol %), L3 (24 mol %), Mn (3 equiv), LiCl (1 equiv),  13  CO 2 (1 atm) in DMF (0. 40 M), at 90 °C. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10. 1021/acscatal. 9b01921. Experimental procedures and characterization data including 1 H,  13.
■ ACKNOWLEDGMENTS We thank  ICIQ, European Research Council  ( ERC-PoC-2016-755251 ), and  MINECO  ( CTQ2015-65496-R ) for financial support. A. T. and F. C. thank  MECD  ( FPU program ) and  China Scholarship Council  ( CSC ) for predoctoral fellowships, and B. S. thanks  European Union's Horizon 2020  under the  Marie Sklodowska-Curie grant agreement  ( 795961 ). We thank  Dr. Noemi Cabello  ( ICIQ-HRMS department ) for mass analysis and  Dr. Yasuhiro Okuda  for conducting initial experiments.
2006a; Mortensen et al. 2011; Sabbagh et al. 2018). NATP, the third identified member of this family of genes in the human genome bears several loss-offunction mutations and transcriptome studies indicate that it is barely if ever transcribed (as shown in the EBI Gene Expression Atlas, entry ENSG00000253937 at www. ebi. ac. uk/gxa/home). One approach to examine hypotheses of recent adaptation in acetylation activity in humans is to investigate the diversity of NAT genes in humans' closest relatives. To this aim, we Sanger sequenced the three members of the NAT gene family in 84 great ape DNA samples, including 68 chimpanzees of the Pan troglodytes verus sub-species (Western chimpanzees). We completed this dataset with 231 NAT sequence genotypes produced with NextGen technology by the Great Ape Genome Project (GAGP)  (Prado-Martinez et al.
Retrieval of NAT sequences or polymorphic positions from public repositories For comparison purposes, we retrieved NAT genotypes from the published unphased genomes of 79 great apes generated in the GAGP by NGS  (Prado-Martinez et al. 2013) , namely from 25 chimpanzees (including a hybrid P. t. verus/troglodytes individual), 13 bonobos, 31 gorillas and 10 orangutans. Two individuals, Harriet (P. t. schweinfurthii) and Boscoe (P. t. verus, Supplementary Figure  S1 ), were in common in the GAGP and CARTA datasets, thus allowing a control of Sanger and NGS sequencing results. We extracted the relevant part of the available VCF files. Further details are provided in Supplementary File S1. All detected polymorphic positions in the Sanger sequenced samples of this study and retrieved from the GAGP VCF files are detailed in Supplementary Tables S3, S4 and S5, for NAT1, NAT2 and NATP, respectively.
To allow comparison of segregating sites at the NAT genes among all hominids (i. e. , all great apes, including humans), we recorded all human polymorphisms reported by the consensus gene nomenclature of human NAT alleles (http://nat. mbg. duth. gr/, accessed in August 2015), complemented with haplotype data from 1000 Genomes Phase 1 (The Genomes Project Consortium 2012) and published data  (Patin et al. 2006a; Sabbagh et al. 2008; Mortensen et al. 2011; Podgorná et al. 2015). These are also reported in Supplementary Tables S3, S4 and S5. Inference of NAT haplotypes in the genus Pan Diploid haplotypes were inferred for all Pan individuals (but not for the other great ape samples, see Supplementary File S1) using PHASE version 2. 1. 1  (Stephens et al. 2001; Stephens and Scheet 2005). The program uses a Bayesian statistical method based on an approximate coalescent model for reconstructing haplotypes from genotype data.
NAT haplotypes in humans A dataset of NAT haplotypes' frequency distributions in human population samples was assembled with published NAT sequences of same length as those of Pan, obtained through a comprehensive literature search at the time of the study. Only populations represented by samples including at least 15 individuals (30 chromosomes) were considered. We thus used published data samples from  Mortensen et al. (2011)  and from  Sabbagh et al. (2008). We also extracted NAT1, NAT2 and NATP phased genotypes from the 1000 Genomes Phase 1 dataset (The Genomes Project Consortium 2012), see Supplementary File S1. In total, the human dataset consists of 20, 18 and 18 samples of unrelated individuals, from human populations distributed on four continents (Sub-Saharan Africa, Europe, East Asia and America), for NAT1, NAT2 and NATP, respectively (Supplementary Table  S7 ).