dataesr/scientific-paragraphs-categorization huggingface dataset:
Microarray experiments Samples were prepared from 500 ng total RNA using the GeneChip WTPLUS Reagent kit protocol and hybridized on Affymetrix four-array strips (HuGene 2. 1 ST array strips). After hybridization (19 h at 48 °C) on the Affymetrix GeneAtlas hybridization station, strips were washed and imaged on the GeneAtlas imaging station. Data were normalized using the expression Console software using default RMA-sketch normalization. Normalized files were analyzed using TAC software (Affymetrix) with default settings. A summary of the results is presented in Additional file 1: Table  S1.
Molecular docking studies For exploring the binding of S2 to site IB of HSA, crystal structure of HSA with idarubicin dimer (PDB code 4LB2) was used. 98 or site IIA, PDB structure of indol amide derivative (PDB code 3LU7) was used. 99 For site IIIA, structure of HSA-diunisal complex (PDB code 2BXE) was used. 88 To dene the receptor site, the residues in sphere of 12 Å around co-crystallized ligand were used. Ligands and water molecules were removed prior to receptor preparation in AutoDock Tools 1. 5. 6. 89 Initial conformation of S2 was generated in OMEGA 2. 4. 3, 90 using MMFF94s force eld. 92 The geometry of lowest energy conformer was further optimized using semiempirical PM6 method implemented in MOPAC 2016. 100  Docking was carried in Autodock Vina 1. 1. 2 soware. 101 VEGAZZ 3. 0.
This was highly consistent with the size determined by DLS and AsFlFFF. No strong variation in this diameter was recorded in comparison to the exact composition of the polymers. DLS also suggested that the hydrodynamical diameters of the particles were more or less constant for all of the polymers selected for this study. Dissolution of Pheo-a within micelles may induce mild swelling of nano-objects as suggested by comparing the diameters of objects with or without Pheo-a, 22 and 27 nm, respectively, for {PEO(2000)-b-PCL(2800)} and 25 and 26 nm, respectively, for {PEO(5000)-b-PCL(4000)}). These data demonstrate that nano-objects are preserved in the presence of Pheo-a. The diameters extracted from the AsFlFFF experiments were quite similar regardless of the analytical method  [34]. Characterization was completed by SANS for some systems in order to gain more insight into the organization of the core/shell (Table  2 ).
5-nm thick shell. SANS results also suggested that dissolution of Pheo-a within the micelles induced a very slight increase in the diameter of the nano-objects. The stabilities of polymeric micelles in solution were assessed in absence of proteins by DLS at 37 °C and 4 °C. The results for empty polymeric micelles are presented in Figure  2. No significant differences were recorded between measurements at low and high temperatures. Intensity mean analysis showed that changes in size remained minor over a time period of more than 14 days. This was consistent with our published results  [35]. The loaded polymeric micelles exhibited the same trend (data not shown).
The mean fluorescence of Pheo-a or fluorescein in intact cells was assessed by flow cytometry. A very low cellular penetration was observed for copolymer micelles labeled with fluorescein (Figure  3A ). This low uptake was attributed to a poor internalization of the micelles, since fluorescence quenching was not observed in a control experiment for this concentration of fluorescein. No significant differences were recorded between measurements at low and high temperatures. Intensity mean analysis showed that changes in size remained minor over a time period of more than 14 days. This was consistent with our published results  [35]. The loaded polymeric micelles exhibited the same trend (data not shown).
Dynamic Light Scattering (DLS) DLS was carried out at 25 °C on a Malvern Zetasizer NanoZS (Malvern Instruments, Orsay Cedex, France). Solutions were analyzed as synthesized without filtration to ensure that undesired populations were not removed. Data were analyzed by the general-purpose non-negative least squares (NNLS) method. The typical accuracy for these measurements was 10%-15%.
Dynamic Light Scattering (DLS) DLS was carried out at 25 • C on a Malvern Zetasizer NanoZS (Malvern Instruments, Orsay Cedex, France). Solutions were analyzed as synthesized without filtration to ensure that undesired populations were not removed. Data were analyzed by the general-purpose non-negative least squares (NNLS) method. The typical accuracy for these measurements was 10%-15%.
Small Angle Neutron Scattering (SANS) SANS experiments were performed with the PACE spectrometer at the Orphée reactor (Laboratoire Léon Brillouin, Saclay, France). Polymer-D 2 O mixtures (polymer concentration 4 mg•mL -1 ) were placed inside quartz cells with a gap of 2 mm at 20 • C. Data were collected in three spectrometer configurations, which were determined by the neutron wavelength and the sample-to-detector distance (12 Å, 4. 7 m), (5 Å, 4. 7 m), and (5 Å, 1. 3 m). The total wave-vector (q) range covered 0. 002-0. 30 Å -1. Scattered intensities were corrected for empty-cell scattering. Detector normalization was performed by dividing data by the scattering from 1 mm of light water. Data were converted to an absolute scale (I(q) = d∑/δΩ, cross-section per unit volume in cm -1 ) with instrument constants provided by LLB and subtracting the incoherent background.
Clinical and laboratory data at presentation Data regarding history, clinical, ophthalmic angiography, and biological findings were collected for all patients. The World Health Organization criteria were used to define hypertension. Laboratory parameters collected were serum creatinine level (SCrl) (n = 41), CRP (n = 41), kalemia (n = 25), blood hemoglobin level (n = 40), eosinophilia (defined as >800. 10 3 /mm 3 ), serum calcium level (n = 31), phosphoremia (n = 29), plasma bicarbonate level (n = 26), albuminemia (n = 26), gammaglobulinemia (n = 35), proteinuria (n = 41), hematuria (defined as >10 4 red blood cells/mL) (n = 41), leukocyturia (defined as >10 4 leukocytes/mL) (n = 36), and glycosuria (n = 41). The estimated glomerular filtration rate (eGFR) was calculated using the simplified modification of diet in renal disease (MDRD) formula.
Follow-up Data regarding renal function (SCrl, eGFR, and need of dialysis), ophthalmic lesions were collected at 1 year when available (n = 35) and at the end of the follow-up in all patients (n = 41). The annual number of attacks was calculated as the ratio between the number of attacks since the 1st symptoms to the duration of follow-up in years (in patients followed for more than 6 months). During the follow-up, treatment (methylprednisolone pulses, oral corticosteroids, local ophthalmic treatments), renal, or ophthalmologic relapses were recorded. A renal or an ophthalmologic relapse was defined as the reappearance of symptoms after a symptom-free period of at least 2 weeks. Patients were categorized into 3 groups according to the initial dose of oral corticosteroids: the "High dose" group, which received an initial dose of 1 mg/kg per d, the "intermediate dose" group, which received 0.
The effect of the interaction between treatment and peak creatinine and treatment choice was tested in both models and dropped if nonsignificant. For these models, multiple imputations of missing data were conducted, if needed. Two-tailed P < 0. 05 was considered statistically significant. All statistical tests were computed using SAS 9. 4 (Cary, NC) and GraphPad Prism version 6. 00 (GraphPad Software, La Jolla, CA).
Questionnaire and measurements The questionnaire was conceived by the authors (a multidisciplinary team in epidemiology, cardiology, pharmacy, with expertise in the domain of patient education) at the light of the literature in the domain of patient educational needs. A pilot investigation involving 20 patients who tested the questionnaire was conducted in January 2014 at the department of cardiology of Saint Antoine Hospital. This pilot study confirmed patient's understanding, feasibility of completion, and resulted in few modifications of the questionnaire proposed to patients in the final survey. The questionnaire included four major sections (see S1 Questionnaire). The first section, on patient demographics, collected data on age, sex, education, and zip code of residence. The second section collected data on treatment characteristics, including anticoagulant name, indication, and time since initiation of treatment.
The third section collected data on patient information requirements. This section was composed of 21 items organized into 5 subdomains: daily management of treatment, theoretical knowledge about the treatment and the disease, impact of treatment on lifestyle, treatment adverse effects, and blood tests to monitor the treatment. Respondents were asked to rate each item through a single choice among 5 proposals: essential, important, of minor interest, unnecessary, and I do not wish to answer this question. Each answer was coded as a score value ranging from 0 to 3 (3 = essential, 2 = important, 1 = of minor interest, and 0 = unnecessary and I do not wish to respond). We calculated a mean score for the 5 subdomains using mean score of each item. For each subdomain, the internal consistency was considered as good (the value of calculated Cronbach's alpha coefficient ranged between 0.
Postmortem evolution of bile To the best of our knowledge, no data are available for the postmortem evolution of bile and its availability at autopsy. Availability may depend on how full the gallbladder is and thus on time of death with respect to mealtime. Moreover, bile may be subject to postmortem processes which could probably affect composition: perivascular diffusion following gallbladder damage, or dehydration. In the Forensic Medicine Institute of Lyon (France), bile could be sampled in 85% of autopsies performed between 2010 and 2013 (personal data).
Acknowledgements We thank  Nathalie Ragozin  ( ARS Rhône-Alpes ) and  Ghislain Didier  ( ARS Rhône-Alpes ) for epidemiological investigation and  Christine Saura  ( Cire Rhône-Alpes ),  Jean-Loup Chappert  ( Cire Rhône-Alpes ) and  Mathieu Tourdjman  ( InVS ) for their comments on the manuscript.
The membranes were then washed three times for 5 min in TBST and two times in TBS. 3 mL of ECL™ Prime Western Blotting System (Sigma-Aldrich) was added to the membranes and incubated for 5 min. The blots were visualised by ChemiDoc™ XRS+ System with Image Lab™ Software (Bio-Rad). After visualisation of p38 MAPK, the membranes were incubated twice for 10 min with in-house dehybridization buffer, twice for 10 min with PBS, and twice for 5 min with TBST, and, after, the protocol was restarted from the blocking of the membrane for the final detection of the -actin (incubation with the primary antibody was during 6 h on +4 ∘ C). The actin band was detected on the same membrane as the p38 MAPK. The signal quantification was done using Image J software. The primary antibodies used were p38 MAPK rabbit anti-human polyclonal antibody (ADI-KAS-MA009-E, Enzo Life Sciences) 1 : 500 and beta-actin rabbit anti-human polyclonal antibody (PA1-183, Thermo Scientific) 1/1000.
Evaluation of Tumour Growth. Tumour growth was measured (tumour length, width, and volume) twice a week by using an external calliper. Tumour volume was calculated by using the following formula:  = Length × Width 2 /2. The mean tumour volume (MTV) per group was estimated and given in the graph. The tumour growth data was recorded for each individually identified rat. The observation period lasted 28 days. All experimental animals were euthanized if during that period the tumour volume reached 4000 mm 3 , as required by institutional guidelines. At the 29th day, rats were removed from their cages, taken to an adjacent room, and within 30 seconds of removal from the cage were euthanized using anaesthetic (Ketamine: 75 mg⋅kg -1 + Xylazine: 8 mg⋅kg -1 ) and an aortic puncture. Immediately after euthanization, tumours were excised, weighed, and snap-frozen in liquid nitrogen and stored at -80 ∘ C.
Statistical Analysis All statistical tests for the in vivo experiments were performed using the statistical package programme SPSS 19 (SPSS Inc. , Chicago, IL). All values were expressed as the mean ± SE. Nonparametric analyses (Kruskall-Wallis test and Mann-Whitney  test) were used in the statistical computations for tumour weight, tumour growth, food intakes, and body weight. Statistical significance between groups for in vitro studies was assessed by the paired Student's -test ( = 3) or repeated measures one-way ANOVA followed by Tukey's posttest (GraphPad Prism, San Diego, California, USA). Differences were considered statistically significant when  < 0. 05.
Value of the data Analyzed dataset for the validation assays of the extraction and quantification of annonacin in the Rat brain is presented. Data comprise the analytical parameters determined, including stability, recovery and matrix effect, using UPLC-ESI-triple quadrupole analysis in SRM mode. Data are in accordance with the bioanalytical validation criteria set by EMA and can be useful for methodological development. They constitute benchmarks for pharmacokinetic studies of sub-type 1b Annonaceous acetogenins.
Carry-over Data for carry-over evaluation were obtained in blank analytical runs following the injection of the upper limit of quantification (ULOQ). The response areas at the retention times of annonacin and of IS were respectively less than 20% of the LLOQ for annonacin and less than 5% for IS, as recommended  [4]. No carry-over was observed during the analysis, as assessed after injection of annonacin at ULOQ, neither for IS at working concentration.
Accuracy and precision Data for the evaluation of accuracy and precision were obtained at 4 concentration levels, including LLOQ (0. 25 ng/g), low (LQC; 0. 5 ng/g), medium (MQC; 5 ng/g) and ULOQ (25 ng/g), with 3 replicates a day, and at two different days. Quality control (QC) samples at 4 different concentrations, including LLOQ and ULOQ, were prepared at 2 different days, with 3 replicates a day, independently of the calibration standards. Within-and between-run precisions were less than 7 15%. Moreover, within-and between-run accuracies were less than 715% of the nominal concentration (Table  1 ).
RNA Isolation and Analysis Total RNAs were extracted using the TRI reagent (Sigma-Aldrich). RNA was then subjected to a reverse transcription-quantitative polymerase chain reaction (RT-qPCR), using the RT kit from Applied Biosystems (Foster City, CA, USA), the fluorescent dye SYBR Green methodology, and an ABI Prism 7300 detector (Applied Biosystems), as described previously  [21]. Gene-specific primers for drug transporters and 18S RNA were used exactly as already reported  [22]. The specificity of each gene amplification was verified at the end of qPCR reactions through analysis of dissociation curves of the PCR products. Amplification curves were analyzed with ABI Prism 7000 SDS software, using the comparative cycle threshold method. Relative quantification of the steady-state target mRNA levels was calculated after normalization of the total amount of cDNA tested to the 18S RNA endogenous reference using the 2 (´∆Ct) method.
Rhodamine 123 Accumulation Assay P-gp activity was determined by measuring intracellular accumulation of rhodamine 123 in MCF7R cells in the absence or presence of P-gp inhibitors, as previously reported  [25]. Briefly, for a typical IC 50 determination experiment, cells were incubated at 37 ˝C with 5. 25 µM rhodamine 123 for 30 min, in the presence or absence of various concentrations of P-gp inhibitors. After washing in phosphate-buffered saline, cells were lysed in distilled water, and intracellular levels of rhodamine 123 were quantified by spectrofluorimetry using a SpectraMax Gemini SX spectrofluorimeter (Molecular Devices, Sunnyvale, CA, USA) (excitation and emission wavelengths were 485 and 535 nm, respectively). Data were expressed as % of rhodamine 123 accumulation in control cells not exposed to P-gp inhibitors, arbitrarily set at 100%.
Data Analysis Experimental data were routinely expressed as means ˘SEM from at least three independent experiments. Statistical analysis of quantitative data was performed with a Student's t-test, analysis of variance (ANOVA), followed by Dunnett's post-hoc test or non-parametric Spearman rank correlation using the Prism software. The criterion of significance was p < 0. 05. Analysis of [I 1 ]/IC 50 and [I 2 ]/IC 50 ratio in relation to relevance or non relevance of clinical DDI studies dealing with P-gp and digoxin was performed using a binary classification decision tree, given a fixed discrimination threshold, resulting in four possible outcomes  [26] : true positive (TP)-in vitro data is in agreement with a relevant clinical digoxin DDI; false negative (FN)-in vitro data is not in agreement with a relevant clinical digoxin DDI; false positive (FP)-in vitro data is not in agreement with a non relevant clinical digoxin DDI; and true negative (TN)-in vitro data is in agreement with a non relevant clinical digoxin DDI.
25. These thresholds are thought to be significant regarding the toxicity of digoxin  [5]  and have consequently been retained in various previous studies  [5, 41, 42, 52]. The remaining 6/26 studies were classified as non relevant DDI (ratio AUCi/AUC < 1. 25 and ratio Cmaxi/Cmax < 1. 25)  [41]. Further, the ratio [I1]/IC50 and [I2]/IC50 were calculated with IC50 values determined from the rhodamine 123 assay for each DDI study (data not shown) and were used to predict P-gp-related DDI for the 26 clinical studies according to FDA criteria ([I1]/IC50 > 0. 1 and/or [I2]/IC50 > 10). Prediction results for the 26 clinical studies are indicated in Table  2. For the 20 clinically relevant DDI, 16 were found to be predicted correctly with IC50 values from rhodamine 123 assays and FDA criteria (Table  2 ), thus resulting in a rather high sensitivity (80.
25. These thresholds are thought to be significant regarding the toxicity of digoxin  [5]  and have consequently been retained in various previous studies  [5, 41, 42, 52]. The remaining 6/26 studies were classified as non relevant DDI (ratio AUCi/AUC < 1. 25 and ratio C max i/C max < 1. 25)  [41]. Further, the ratio [I 1 ]/IC 50 and [I 2 ]/IC 50 were calculated with IC 50 values determined from the rhodamine 123 assay for each DDI study (data not shown) and were used to predict P-gp-related DDI for the 26 clinical studies according to FDA criteria ([I 1 ]/IC 50 > 0. 1 and/or [I 2 ]/IC 50  > 10). Prediction results for the 26 clinical studies are indicated in Table  2. For the 20 clinically relevant DDI, 16 were found to be predicted correctly with IC 50 values from rhodamine 123 assays and FDA criteria (Table  2 ), thus resulting in a rather high sensitivity (80.
480 (5) C7-O1 1. 202 (4) C2-C3 1. 378 (5) C7-C8 1. 546 (6) C2-N1 1. 401 (5) C8-O2 1. 208 (5) C3-C4 1. 381 (5) C8-N1 1. 363 (4) IUCrData (2016). 1, x160792 IUCrData (2016). 1, x160792 data-3.
Sequencing was performed using MiSeq Reagent Kit v3 chemistry according to the manufacturer's instructions and the fastq files generated as an Illumina sequencing output were uploaded into Qiime software  [11]. Quality trimming criteria were set to a value of 19, with no mismatch in the MID sequences and maximally 1 mismatch in the primer sequences. Chimera were identified and excluded by slayer algorithm  [12]. The sequences were then classified with RDP Seqmatch with an operational taxonomic units (OTU) discrimination level set up to 97%. The raw sequence reads have been deposited in the NCBI Short Read Archive under the accession number SRP078556.
For each analysis, 5 μg of peptide sample was used. Each sample was separated on an EASY Spray C18 column (length 25 cm, I. D. 75 μm, particles 3 μm) using 300 nl/ min flow rate of solvent A (0. 1% formic acid) and solvent B (0. 1% formic acid in 20/80 H 2 O/ ACN (vol/vol)) and 150 min long reverse-phase gradient with concentration of solvent B increasing from 4% to 40%. From MS spectra (Orbitrap analyzer, 30,000 FWHM resolution, mass range 390-1700 m/z), the 10 most intensive peptides were fragmented using CID fragmentation (normalized collision energy 35) followed by MS/MS scan (LTQ analyzer). Raw LC-MS/MS data were analyzed using Proteome Discoverer v1. 4. MS/MS spectra identification was performed by the SEQUEST algorithm using chicken protein sequence database. For each search, precursor and fragment mass tolerance were 10 ppm and 0.
Mitochondrial Respiration Mitochondrial oxygen consumption was measured using the high resolution Oxygraph-2K (OROBOROS instruments, Innsbruk, Australia). In two sealed thermostated chambers  (37 ˝C)  with continuous stirring at a constant temperature of 37 ˝C, freshly isolated mitochondria (200 µg protein) were incubated in 2 mL of the respiratory medium MIRO5 (0. 5 mM EGTA, 3 mM MgCl 2 ¨6H 2 O, 65 mM KCl, 20 mM taurine, 10 mM KH 2 PO 4 , 20 mM HEPES, 110 mM sucrose, and 1 g/L BSA, pH 7. 1). State 4 respiration (resting) was initiated by adding 5 mM glutamate and 2. 5 mM malate. Subsequent addition of 0. 5 mM ADP generated glutamate and malate supported state 3 (ADP stimulated respiration). Data acquisition and analysis was performed using Oxygraph-2K-DataLab software version 4. 3. 2. 7 (OROBOROS instruments, Innsbruk, Austria).
Gene specific primers for target genes were designed using Primer Express Software (CYP2E1 forward: 5'-TTCCAACCTACCCCATGAAG-3'; reverse: 5'-GAGGGAGTCCAGAGTTGGAA-3'), (GSTpi forward: 5'-GCCATCTTGAGGCACCTG-3'; reverse: 5'-CACCCCATCATTCACCATATC-3') and (TNF-α forward: 5'-TGAACTTCGGGGTGATCG-3'; reverse: 5'-GGGCTTGTCACTCGAGTTTT-3'). Normalization was performed from simultaneous amplification of a ß-actin gene fragment (forward: 5'-AATCCTGTGGCATCCATGAAAC-3'; reverse: 5'-CGCAGCTCAGTAACAGTCCG-3'). The real time PCR conditions were as follow: after an initial denaturation step for 3 min at 95 ˝C, 40 cycles of 95 ˝C for 10 s and 60 ˝C for 30 s. Melting point dissociation curves were performed between 65 ˝C and 95 ˝C (temperature transition of 0. 5 ˝C) to confirm that only a single product was amplified.
Statistical Analysis Experimental results are presented as means ˘SD. A Student's t test was used to compare the total polyphenol content between the n-BuOH extracts from Gq and Tp. For the other experiments, statistical analyses were performed using a one way analysis of variance (ANOVA) followed by a Fisher's test using the statistical package GraphPad Prism. For all tests, the statistical significance was set at p < 0. 05.
To better identify the polyphenolic compounds of Gq and Tp extracts (phenolic acids, flavonoids) whose antioxidant and hepatoprotective effects have already been the subject of numerous studies, we proceeded to a TLC-fingerprint analysis of the Gq and Tp extracts. Presence of flavonoids and phenolic acids as the predominant compounds in Gq and Tp extracts, respectively, may contribute to the high TPC of these species. These results have been confirmed by HPLC chromatogram analyses of Gq and Tp extracts (ZB, data not shown). As the antioxidant potential of polyphenolic compounds in plant belonging to the genus Genista and Teucrium has been reported in a number of in vitro studies  [22, 23, 32, 36, 57] , these results prompted us to screen antioxidant activity and hepatoprotective effects of polyphenolic extracts from Gq or Tp in rats submitted to APAP overdose.
Acknowledgements We dedicate this article to our friend  Julien Cren  (in memoriam). This work was financially supported by a grant from the  Institut de Veille Sanitaire  (grant CNR paludisme). French National Reference Centre for  Imported Malaria Study Group V Augis ,  D Basset ,  F Benoit-Vical ,  A Berry ,  N Bourgeois ,  F Conquere de Monbrison ,  P Delaunay ,  J Delmont ,  K Ezzedine ,  B Faugere ,  C Garabedian ,  E Garnotel ,  C Lollivier ,  D Malvy ,  P Marty ,  D Maubon ,  G Menard ,  P Millet ,  P Minodier ,  A Mottard ,  P Munier ,  P Parola ,  R Piarroux ,  S Picot ,  T Pistone ,  C Pomares-Estran ,  J Puyhardy ,  D Raffenot ,  M-C Receveur ,  R Saidi ,  H Savini ,  F Simon ,  S Vedy.