dataesr/scientific-paragraphs-categorization huggingface dataset:
Anthropometric measurement data were collected based on the standard procedure of nutritional assessment of height and weight while serum creatinine was measured by the hospital laboratory accredited with 2-3 stars by the EPHI. Using Medicalc android application GFR-cg, and MDRD-4 were calculated and subjects were classified into NKF K/DOQI classification. Descriptive and analytic statistics were done using software of SPSS version 20 for AOR for associated factors by the crosstab. Results: Out of 111 total study subjects, 96 clients' serum Creatinine were measured and CrCl. The prevalence of normal stage 1 GFR (90-131 ml/min) was 24. 3% (n=27) while 16. 2% (n=18) have reduced (60-89 ml/min) stage 2 mild renal disease by GFR-cg. Among factors associated with stage 2 mild decline of GFR are BMI less than 18.
56, 1. 67). The absolute configuration of 2 was determined to be 2R, 3S, 6S, 7R, and 10S by ECD analysis. As compound 1, two Cotton Effects (CE) from the n→π* transition of the α,β-unsaturated lactone were revealed at 225 and 275 nm with alternative signs (Figure  5 ). The complete assignment in conjunction to the data found in the literature led to identify compound 2 as new trixane congener (Figure  2 ). The trivial name jungioside B was given. The NMR data of 3 revealed signals of a β-D-glucopyranosyl (δ 4. 39/104. 8, 3. 27/74. 8, 3. 24/77. 1, 3. 33/70. 9, 3. 37/76. 5, 3. 55 and 3. 69/62. 1) as found in the above-mentioned compounds and signals of fifteen carbons suggesting another sesquiterpene bearing a sugar moiety. The diagnostic of 2D experiments permitted to identify the aglycone as a guaiane-type sesquiterpene whose the structure was consistent with 6-hydroxyguaiane previously reported  [39].
The spectra were recorded using deuterated solvents CDCl 3 and CD 3 OD. Chemical shifts (δ) are expressed in ppm with reference to the TMS signal (δ H /δ C 0. 0) and coupling constants are reported in Hz. The 2D NMR experiments (COSY, HSQC, HMBC, and NOESY) were performed using standard Bruker microprograms. UPLC-PDA analyses were performed on a Waters Acquity H UPLC quaternary system manager equipped with a Acquity sample manager and a PDA detector. Data were processed with Empower 3 software. CPC separation was performed on a SCPC-250+1000-B apparatus provided by Armen Instrument (Saint-Avé, France) fitted with a 1000 mL rotor containing 2016 twin-cells, equipped with a gradient pump and a 50 mL loop injection 6-way valve. Electronic circular dichroism (ECD) spectra were recorded in acetonitrile using a Jasco XLC 3195CD detector.
Computational details (ECD) All calculations were conducted using Gaussian 09W  [41]. After geometry optimization using density functional theory (DFT) at the B3LYP/6-311+g (d,p) level of theory. A check for imaginary frequencies was performed in order to confirm the presence of a real minimum. Calculations of the rotational strengths and excitation energies were realized using time dependent (TD) DFT at the same level of theory. ECD spectra were plotted using the SpecDis v1. 61 software  [42].
Acknowledgements The authors thank the  FP7-PEOPLE-2010-IRSES Marie Curie Actions, program  ''ChemBioFight'' (exploring CHEMical BIOdiversity with innovative approaches for FIGHTing Chagas and leishmaniasis, grant number  269031 ) for financial support. Prof. A. -L. Skaltsounis  and  Dr. Maria Halabalaki  are gratefully acknowledged for the management of the program. The authors declare no conflict of interest.
DNDGIC Binding Triggers a Strong Negative Cooperativity in Many GSTs-In the present study 16 different GSTs, as representative members of the Tyr-, Ser-, and Cys-GST subfamilies, were examined in relation to their interaction with DNDGIC. Data reported in Table  1  show that almost all tested Tyr-GSTs and Ser-GSTs display a noticeable negative cooperativity for DNDGIC binding with Hill coefficients, n H, ranging from 0. 51 to 0. 75 (Table  1 ). If the adjacent subunit is still catalytically active in the half-saturated GSTs, this behavior would warrant a FIGURE 1. A, chemical structure of the dinitrosyl-diglutathionyl iron complex (DNDGIC). B, crystal structure of DNGIC bound to GSTP1-1 (one GSH is replaced by a Tyr residue, which completes the coordination shell of the iron ion with its -OH group).
The structure is from PDB ID 1ZGN, the protein is in green ribbons, whereas DNGIC and Tyr-7 are depicted in ball-and-stick colored according to atom type  (27). c For these GST variants the fits are essentially monophasic, and then the dissociation constants K D1 ϭ K D2. residual conjugating activity even in the presence of a large amount of DNDGIC, i. e. in the case of relevant NO production in the cell. Notably, the Hill coefficients found for a few Tyr-GSTs approach the value of 0. 5, which is the highest degree of negative cooperativity commonly observed in a dimeric enzyme  (28). None of the GSTs taken as representative members of the Cys-GSTs subfamily shows any cooperativity (Table  1  and Fig. 2 ). Thus, these GSTs, all close to the ancestral precursor of GSTs, not only display 3 orders of magnitude lower affinity for DNDGIC than the Tyr-and Ser-GSTs but also lack any detectable intersubunit communication necessary for cooperative modulation.
4)   where Y is percent of inhibition or percent of fluorescence quenching. GST Activity-GST activity was assayed by incubating 0. 1 mM GSH and 1 mM CDNB in 0. 1 M potassium phosphate buffer, pH 6. 5 (25 °C). The reaction was followed spectrophotometrically at 340 nm, where the CDNB-GSH adduct absorbs (⑀ ϭ 9600 M Ϫ1 cm Ϫ1 ). Structural Studies-Illustrations of X-ray structures were created by UCSF Chimera  (56). PDB ID used to identify interface connectivities were: hGSTP1-1, 6GSS; hGSTA1-1, 1K3L; The residue numbering of all these GSTs is those reported in the Protein Data Bank. In this library only human GSTP1-1, GSTA1-1, and GSTM2-2 sequences do not display Met-1. Statistical Data Analysis-Kinetic and thermodynamic data were analyzed and displayed by GraphPad Prism software (La Jolla, CA).
2WJU; hGSTA3-3, 1TDI; hGSTM2-2, 2AB6; O. volvulus GST2, 1TU8; S. haematobium GST, 1OE7; L. cuprina GSTc (Parker, personal communication); A. dirus GSTD3-3, 1JLV; A. dirus GSTD4-4, 3F63; A. dirus GSTD5-5, 1R5A; hGSTT2-2, 3LJR; O. anthropi GST, 2NTO; B. xenovorans GST, 2DSA; S. paucimobilis GST, 1F2E; P. mirabilis GST, 2PMT. Finally, hGSTP1-1 with DNGIC was derived from PDB ID 1ZGN.
hGSTA2- 2 , 2 2WJU; hGSTA3-3, 1TDI; hGSTM2-2, 2AB6; O. volvulus GST2, 1TU8; S. haematobium GST, 1OE7; L. cuprina GSTc (Parker, personal communication); A. dirus GSTD3-3, 1JLV; A. dirus GSTD4-4, 3F63; A. dirus GSTD5-5, 1R5A; hGSTT2-2, 3LJR; O. anthropi GST, 2NTO; B. xenovorans GST, 2DSA; S. paucimobilis GST, 1F2E; P. mirabilis GST, 2PMT. Finally, hGSTP1-1 with DNGIC was derived from PDB ID 1ZGN.
Thus, the variability in published DILI annotations, each utilizing different schema and data sources, is an impediment for the development of predictive in vitro models. The classification of DILI negative compounds is even of more concern. Most published approaches that define a drug as DILI negative depend on search results from PubMed or other databases  [60, 61, 70, 71, 113]. In some studies  [115] , drugs were labeled DILI negative if they simply were without searchable results for a specific DILI adverse event (e. g. , acute liver failure). However, due to the diverse manifestations of clinical DILI and the severe underreporting of DILI cases  [68] , these approaches may miss the information necessary to designate a drug as DILI negative. In a recently published survey, 7. 9-41. 8% of drugs defined as DILI negative in published datasets were verified as the cause of DILI in case reports in which causality had been fully justified  [65].
The comprehensive information contained in drug labels is especially useful for limiting false negative DILI compounds  [65]. Secondly, the procedures of the DILI-label based annotation approaches are transparent and reproducible, and the data source (i. e. , drug label and causality evidence) can be updated with the advance of DILI knowledge. Thirdly, the annotations and dataset have been extensively applied to develop in silico  [64, 116] , in vitro  [49, 62, 63, 71, [117] [118] [119] [120] , and in vivo models  [121] [122] [123] [124]  and were also recommended as the standardized list for model validation  [95].
The proposed paradigm would shift the emphasis from the present approach that strongly relies on QTc prolongation and would obviate the need for the clinical Thorough QT study during later drug development. The Comprehensive In Vitro Proarrhythmia Assay (CIPA), an integrated nonclinical in vitro/in silico paradigm, was initiated toward these aims  [142]. CIPA consists of three components aiming to (1) test the effect of compounds on different cardiac ion channels, (2) develop in silico models on cardiac action potential by integrating the ion channel dataset, and (3) measure action potential in human stem cell-derived ventricular cardiomyocytes. What Can Be Learned from the Current CIPA Initiative to Help the In Vitro DILI Field? International consensus on assay protocols, method standardization, and validation will need to be implemented in a new guideline  [142].
MIAME has not only facilitated data sharing but also guided software development  [145]. In 1999, the Microarray Gene Data Expression Society (MGED) was founded with a basic aim to standardize the field  [146]. In addition, MGED asked for the depositary of primary experimental data into a permanent public database. In 2002, the MGED society convinced high impact scientific journals such as Nature, The Lancet, and Cell to require MIAME for publication of microarray results  [146]. What Can Be Learned from the MIAME Initiative to Help the In Vitro DILI Field? In 2006, a thorough analysis of widespread microarray platforms by a multicenter consortium demonstrated intraplatform consistency across test sites, as well as a high level of interplatform concordance in terms of genes identified as differentially expressed  [147].
Since the majority of scientific journals require that raw and normalized microarray data be accessible to the public at the time of publication, a significant number of datasets are publicly available  [148]. The technology has been successfully used for disease diagnosis and prognosis, human disease subtype classification, and therapeutic treatment selection. Overall, the efforts to standardize the microarray field enabled microarray-based gene expression profiling to evolve into a mature, high-throughput, analysis approach that has been extensively applied in biomedical and clinical research for more than 20 years  [149]. We believe that the efforts provided in the microarray field could also be used as a relevant example for the in vitro DILI community.
Strategies to Reduce Rate of False Positive in the In Vitro Genotoxicity Field. In vitro genetic toxicology tests are performed for regulatory purposes to predict carcinogenic potential of drugs, chemicals, food additives, and cosmetic ingredients. If a chemical is positive in one of the battery of assays, in vivo genotoxicity studies are often performed to better assess carcinogenic risk for humans. Kirkland et al. [150]  evaluated the performance of a battery of three in vitro genotoxicity assays to discriminate rodent carcinogens and noncarcinogens from a large database of over 700 chemicals and found that 93% of rodent carcinogens were detected by the assay battery. Nevertheless, approximately 80% of the 177 noncarcinogenic compounds tested gave a false positive result in at least one in vitro test  [150].
The low specificity data highlighted the need for more meaningful in vitro genotoxicity tests or practical interpretation of current positives. In order to address the high rate of false positive results, a 2-day workshop was hosted and sponsored by the European Centre for the Validation of Alternative Methods (ECVAM) in 2006  [150]. What Can Be Learned from the ECVAM Initiative to Help the In Vitro DILI Field? The recommendations of the experts were to use cell systems that are p53 and DNA-repair proficient, with defined phase I and phase II metabolic capacities, and to reduce the top concentrations and the maximum level of cytotoxicity to reach  [150]. A few years later, Kirkland et al. [151]  published recommendations on chemicals that would be appropriate to evaluate the sensitivity and specificity of new/modified mammalian cell genotoxicity tests, in particular, to avoid misleading positive results.
Acknowledgments This work was supported by an  NIH  grant ( HL48044 ) and an  AHA postdoctoral fellowship  ( 12POST12040390 ). We would like to acknowledge  Dong-Ju Shin ,  Vicki Troelscht ,  Heike Baecker , and  Eric Wilson  for their technical contributions to this work. Also, we would like to acknowledge  Wei Yuan Hsieh  for helping design the graphical.
Circular Dichroism (Far-UV) Spectroscopy CD spectra were recorded on an Aviv 215 spectropolarimeter (Aviv Biomedical, Lakewood, NJ, USA) with protein samples at 0. 7-1. 4 mg¨mL ´1 in Hepes 20 mM NaCl 150 mM TCEP 1 mM. Far-UV CD spectra were recorded between 195 and 260 nm using a cylindrical cell with a 0. 02 cm path length, an averaging time of 1 s per step and bandwidth of 1 nm. Three consecutive scans from each sample were merged to produce an averaged spectrum and corrected using buffer base lines measured under the same conditions. Data were normalized to the molar peptide bond concentration and path length and expressed as mean residue ellipticity ([θ] degree¨cm 2 ¨dmol ´1) as described elsewhere  [44]. The catalytic domains corresponding to amino acids 1-543 (TcsL 1-543), 1-93 and 19-93 from TcsL-82, were cloned in a pEGFP-C1 vector (Clontech, Saint-Germain-en-Laye, France) in BglII and PstI restriction sites.
Delivery of TcsL-cat and Mutants into Cultured Cells by Electroporation The recombinant TcsL-cat or TcsL mutant was delivered into HeLa cells by electroporation. HeLa cells were detached with versene and 10 6 viable cells were incubated with 5 µg toxin in electroporation buffer (20 mM Hepes, 1 mM NaHPO4, 5 mM KCl, 140 mM NaCl, 10 mM glucose). The amount of protein used for electroporation was selected on the basis of dose-response proliferation assay results (data not shown). Cells were then incubated on ice for 10 min and electroporated at 160 V, 500 µF and infinite resistance (BioRad GenePulser X-cell), in 0. 2 cm electroporation cuvettes (BioRad, Marnes-la-Coquette, France). Cells were placed on ice for 10 min then suspended in 2 mL of medium and 100 µL transferred in 96-well plate (TPP).
BC area quantification. The BC area quantification was based on ZO-1 protein immunolabelling and phase-contrast images. ZO-1 immunolabelling. After capturing the ZO-1 protein immunofluorescence images, the BC were quantified using the Cell Health Profiling V4 bio application of the ArrayScan software (Thermo Scientific). Segmentation was performed by adjusting the shape, area and brightness parameters to eliminate non-corresponding objects. Based on their areas (labelled objects), the BC were classified into 3 categories: 20-50, 50-100 and > 100 μm 2 (Supplementary Fig. 1 ). An analysis was performed on 10 images per condition. Phase-contrast images. The mean BC areas were determined from 3 zones per condition using ImageJ 1. 48 software at T0 and after 3 h of compound exposure. Briefly, after capturing the time-lapse images, bright objects corresponding to BC were segmented by adjusting the shape and area parameters to exclude non-corresponding objects.
Aliquots containing an equivalent total protein content as determined by the Bradford procedure with bovine serum albumin as the standard were subjected to sodium dodecyl sulfate/12% polyacrylamide gel electrophoresis, electrotransferred to Immobilon-P membranes, and incubated overnight with primary antibodies directed against p-MLC2 and total MLC2 (dilution: 1/1000). After exposure to horseradish peroxidase conjugated anti-mouse/rabbit antibody (dilution: 1/5000) (Dako, Les Ulis, France), the membranes were incubated with a chemiluminescence reagent (Millipore, Billerica, MA, USA) and the bands were then visualized with Fusion-Capt software (Vilber Lourmat, Marne La Vallée, France) and quantified using ImageJ 1. 48.
Acknowledgements We are grateful to  Pr Alan Hoffmann  ( San Diego, CA ) for the gift of NBD-UDCA fluorescent analogue. This work was supported by the  European Community  [Contract  MIP-DILI-115336 ]. The  MIP-DILI  project has received support from the  Innovative Medicines Initiative Joint Undertaking , resources of which are composed of financial contribution from the  European Union 's  Seventh Framework Programme  [ FP7/20072013 ] and EFPIA companies' in kind contribution. http://www. imi. europa. eu/. Ahmad Sharanek  was financially supported from the  Lebanese Association for Scientific Research (LASeR)  and the  MIP-DILI  project;  Audrey Burban  by the  MIP-DILI  project and  Matthew Burbank  by a CIFRE contract with Servier.
Questionnaire In order to prepare a data collection questionnaire, initial literature was searched following which discussions were carried out to prepare a more refined version of the questionnaire. The questionnaire was internally consistent (Cronbach's a ¼. 88). The questionnaire was prepared having 5 sections: (a) sociodemographic details, (b) knowledge, (c) sources of knowledge, (d) actual herbal drug use experience, and (e) perceived risks, benefits, and barriers. The 9 selected herbal drugs were saffron (Crocus sativus), borage (Borago officinalis), citrus aurantium (Citrus aurantium), thyme (Thymus vulgaris), chamomile (Matricaria chamomilla), lavender (Lavandula angustifolia), valerians (Valeriana officinalis), hypericum (Hypericum perforatum), and ginseng (Panax ginseng).
Molecular detection of selection of antibiotic resistance A part of the bacterial suspension from relapsing mice was inactivated at 95°C during 30 min, to allow bacterial DNA extraction by heat shock (5 cycles of 2 min at 95°C and 2 min at 4°C) following by 15 min at 95°C and 15 min in an ultrasonic bath. IllustraTM PuReTaq Ready-To-Go PCR beads (GE Healthcare) was used to perform PCRs. For the rpoB gene, we used primers as previously reported  [17]  RPOBMuS 5'-GCGCACGGT GGGTGAGCTG-3' RPOBMuAS 5'-CGAGACGCCCTACCGCAAGG-3'. Other primers were designed according to information on the complete genome of M. ulcerans (GenBank accession number CP000325): for the gyrA gene, MugyrAS 5'-CGCCGTGTGCTCTATGCCATG-3' and MugyrAAS TCGCCGGGTAATGACCCGCCA-3' , and for the ARN23S gene 23. 1, 5'-AATGG CGTAACGACTTCTCAACTGT-3' and 23.
However, it lacks of sterilizing effect when compared to the other regimens in the present experiment, although the differences did not reach statistical significance (p>0. 05). This lack of sterilizing activity has been already reported in a previous study where the reduction in the RIF-STR dosing frequency from 7/7 to 5/7 led to a relapse rate of 12% in the mouse model  [18]. In the present study, the intermittent 2/7 or 3/7 fully oral regimens were as active as the control oral regimen (RFP-CLR 5/7). We confirm by the present study that the latter regimen is sterilizing in the mouse model (a single relapse among 40 mice), as previously found in the same model of established infection  [7]  as well as in a model of incubating infection  [20]. Therefore, the RFP-CLR 5/7 regimen is worth comparing to the daily RIF-CLR oral regimen, which has been successfully tested in the field  [10]  and is currently evaluated in a clinical trial (NCT01659437, clinicaltrials.
ACKNOWLEDGMENTS HLW was supported by doctoral scholarships from the  Indonesian ministry of education (Directorate Generale of Higher Education, DGHE)  and the  French government (Bourse Du Gouvernement Français, BGF). EH was supported by a doctoral scholarship from  La ligue contre le Cancer. ABS was supported by  Miguel Servet program (ISCIII). CR is supported by a doctoral scholarship from  Fondation Philanthropia. AM was supported by a postdoctoral fellowship from  Agence Nationale pour la Recherche (ANR). AO was supported by  Intensification of Research Activity Program (ISCIII/Agencia Laín-Entralgo/CM). GK is supported by the  Ligue contre le Cancer  (équipe labelisée);  Agence National de la Recherche (ANR) -Projets blancs ;  ANR  under the frame of E-Rare-2, the  ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC) ;  Cancéropôle Ile-de-France ;  Institut National du Cancer (INCa) ;  Institut Universitaire de France ;  Fondation pour la Recherche Médicale (FRM) ; the  European Commission (ArtForce) ; the  European Research Council (ERC) ; the  LeDucq Foundation ; the  LabEx Immuno-Oncology ; the  SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE) ; the  SIRIC Cancer Research and Personalized Medicine (CARPEM) ; and the  Paris Alliance of Cancer Research Institutes (PACRI).
Purification by flash chromatography (petroleum ether/Et 2 O 80:20) afforded a mixture of enantiopure acetal diastereoisomers 73 (9. 57 g, 25. 2 mmol, 80%) as a pale yellow solid. An analytical sample of pure diastereomers was obtained from racemic material. Data for trans-73: R f 0. 59 (petroleum ether/Et 2 O 80:20); mp 86 °C (CHCl 3 ); IR (neat cm -1 ) 3060 (w), 2903 (w), 1125 (s), 1088 (s), 897 (s); 1 H NMR (400 MHz, CDCl 3 ) δ 7. 99-7. 95 (1H, m, H Ar ), 7. 94-7. 83 (3H, m, H Ar ), 7. 59 (1H, dd, J = 8. 5, 1. 6 Hz, H Ar ), 7. 56-7. 50 (1H, m, H Ar ), 6. 16 (1H, s, CHOO), 4. 83 (1H, dddd, 3 J HF = 17. 4, 3 J HH = 7. 2, 3 J HF = 6. 8, 3 J HH = 6. 6 Hz, CHCF 2 ), 4. 49 (1H, dd, 2 J HH = 9. 2, 3 J HH = 7. 2 Hz, CHHCHO), 4. 34 (1H, dd, 2 J HH = 9. 2, 3 J HH = 6. 6 Hz, CHHCHO);  13  C NMR (101 MHz, CDCl 3 ) δ 134.
■ ACKNOWLEDGMENTS The  European Community  ( INTERREG IVa Channel Programme, IS:CE-Chem , project  4061 ) and  EPSRC  (core capability  EP/K039466/1 ) are thanked for financial support. We thank  Dr. Graham Tizzard  of the  EPSRC UK National Crystallography Service at the University of Southampton 52  for the collection of the crystallographic data and structure refinement of compound cis-73. Apollo Scientific  is gratefully acknowledged for a gift of 4-bromo-3,3,4,4-tetrafluorobut-1ene.
, 2010; Zi et al. , 2015; Araújo et al. , 2016). For the mouth, the Human Oral Microbiome Database lists 1,200 predominant oral species, with some 19,000 phylotypes  (Keijser et al. , 2008) , and with distinct subsets predominating in different habitats  (Xu et al. , 2015). Due to its unusual anatomy between adjacent teeth and the gingival tissue, the interdental space -in fact the 30 interdental spaces for an individual -is a huge source of bacteria  (Cafiero and Matarasso, 2013). This space favors the development of periodontal diseases in adults because the access required to disrupt the biofilm by toothbrushing and saliva is restricted  (Dentino et al. , 2013). Periodontitis affects millions of people each year  (Darveau, 2010). Periodontitis is considered a polymicrobial inflammatory disease and is characterized at its onset by a synergistic and dysbiotic microbiota, within which different members or specific gene combinations fulfill distinct roles that converge to shape and stabilize a disease-provoking microbiota  (Darveau, 2010; Hajishengallis et al.