dataesr/scientific-paragraphs-categorization huggingface dataset:
RNA Extraction and Analysis Total RNAs were extracted with the TRI-Reagent kit (Euromedex, Souffelweyersheim, France), according to the manufacturer's instructions. Total RNA was subjected to real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR) analysis, as described in Reference  [22]. Primers were designed using Primer Express software (Applied Biosystems, Courtaboeuf, France) and validated by testing PCR efficiency using standard curves (85% ≤ efficiency ≤ 115%). Gene expression was quantified using the comparative C T (threshold cycle) method on a StepOnePlus system (Applied Biosystems). TATA box Binding Protein (TBP) expression was used as a reference. A list of the primers used for the Real Time Quantitative Polymerase Chain Reaction (RT-QPCR) is provided in the Supplementary Table.
2+ ]i, were monitored using a Nikon microscope (TiU) equipped with an EM-CCD (Luca-S) camera for real-time recording of digital images and an S-fluor 40× oil immersion objective (Nikon, Tokyo, Japan). Different test and control solutions were added alone or in combinations to the WillCo-dish wells. Images were taken at Z intervals of 0. 3 mm and were analyzed using NIS-Elements software (Nikon, Tokyo, Japan). The changes in [Ca.
Licking and two bottle preference test The licking test consisted of subjecting a mouse to different solutions to determine the number of licks given on a feeding bottle by using a contact lickometer (Med Associates, St. Albans, VT)  (26). Mice were deprived of food and water for 6 h before the test, which took place 6 h after beginning of the dark period. After a training period, which was required to learn the procedure, mice were randomly subjected to a bottle that contained either control, TUG891 (100 M), LA (0. 2%), or both for 15 min. In this experiment, data were analyzed for only 1 and 5 min from first lick. The experiments on the spontaneous preference for lipidenriched solutions were performed by a two-bottle preference test according to previously described procedures (3). The mice were deprived of water for 6 h before the start of the experiment.
Nuclear magnetic resonance (NMR) spectroscopy NMR spectroscopy was performed in 5 mm diameter tubes in DMSO-d 6 at 25 °C. 1 H and 13 C NMR spectroscopy was performed on a Bruker Avance 300 spectrometer at 300 MHz ( 1 H) and 75 MHz ( 13 C), respectively. The chemical shift scale was calibrated based on the internal solvent signals (δ = 2. 50 ppm for DMSO-d 6 and δ = 7. 26 ppm for CDCl 3 ). Data were reported as: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, br = broad), coupling constants (J) given in Hertz (Hz), and integration.
, 2018). Among the three VIM-5 positive isolates, one of them i. e. P. suwonensis 191B isolate which was obtained from a stool sample of a patient with acute gastroenteritis, for which no genome of this bacterial species is available in public sequence databases, was subjected to whole genome sequencing using Illumina MiSeq technology (Illumina, San Diego, CA, USA). The raw sequence was assembled using the Spades software and annotated by the Prokka bacterial genome annotation pipeline  (Bankevich et al. , 2012; Seemann, 2014). The Plasmid incompatibility (Inc) groups and acquired antibiotic resistance genes   were determined using the PlasmidFinder 2. 0 platform and ARG-ANNOT, respectively  (Carattoli et al. , 2014; Gupta et al. , 2014). P. suwonensis 191B Stool R R R R R R R R S R S R R R I S blaVIM-5 A.
Data analysis The pharmacokinetic parameters of ART after intravenous administration were determined from the obtained plasma concentration-time data by using non-compartmental pharmacokinetic analyses by Macro-Excel software. The trapezoidal method was used to calculate the area under the curve (AUC) of plasma concentration as a function of time and the total area under the first moment curve up to last time point (AUC0→t). The area under the curve of the plasma concentrations to the first moment up to infinite time (AUC0-∞) is obtained by extrapolation on the lower limits. Delta AUC represents the value of the extrapolation. The elimination rate constant (ke) was calculated by the semi-logarithmic regression analysis from the slope of the line. The half-life (t1/2) of the drug was obtained by dividing 0.
693 by ke. The total clearance was calculated by dividing the dose administered by AUC0-∞. The volume of distribution was calculated using the equation Vd = CL/k. The maximum plasma concentration (Cmax) and the time to reach this maximum (Tmax) were directly determined. The plasma concentration values as a percentage of the injected dose were also calculated. All data are expressed as mean value ± standard deviation (SD). Statistical analyses were performed using one-way ANOVA test, and the level of significance was set at 5%.
Acknowledgments 14 The authors thank  Christine Brunet-Manquat ,  Delphine Levilly  (DPM), and  Emeline Lemarie  ( HP2 ) for their technical assistance, as well as the  NanoBio-ICMG Platform (FR 2607, Grenoble)  for granting access to the  Electron Microscopy facility. We also thank the  French Embassy in Burkina Faso  for the financial support of  J. B. G. Yaméogo. This work has also been partially supported by grants from  Agence Nationale de la Recherche  (grant # ANR-11-BS10-0007 ) and  LabEx ARCANE  ( ANR-11-LABX-0003-01 ).
HPLC program (also see Strategic Planning and Basic Protocol 5) The analysis of adenosines is performed by reversed-phase HPLC on a Hyperclone C18 (ODS) column connected to an HPLC system (Dionex). The HPLC analysis is carried out as described previously  (Estavillo et al. , 2011). The gradient for separation of adenosine derivatives is optimized as follows: equilibration of column for 0. 2 min with 95% (v/v) of running buffer A (Table  2 ) and 5% (v/v) running buffer B (Table  3 ), linear gradient for 53 min up to 50% (v/v) of running buffer B, and re-equilibration for 7 min with 5% (v/v) running buffer B. The flowrate is set to 0. 8 ml/min. See Basic Protocol 5 for data interpretation.
Data analysis 1. In the ATP/ADP/AMP measurement (Basic Protocol 2), we use 200 μl extraction buffer and 15 μl reaction buffer. 10-μl samples are injected into the column. Here we use ATP as the example and the analysis ADP or AMP methods are same as for ADP (Fig. 3A ). 2. First, we analyze the ATP standards from the HPLC and get the values of slope and blank (Fig. 3B ). 3. After we get the slope, we can calculate concentrations within samples as shown in Fig. 3C. Briefly, the reaction concentration is calculated as (valueblank)/slope and normalized by dilution factor and fresh weight (FW). Normally, the final level is   normalized to provide a value with the units μmol/gFW (Fig. 3C ), where gFW refers to the fresh weight of the plant material in grams. 4. Similarly to the ATP analysis, the concentrations of pyrimidine nucleotide are also normalized from the standard.
Here, we use NAD + as an example (Fig. 4A ). 5. We first use the raw data of the standard to get the slope and V blank (Fig. 4B ). 6. After we get the slope, we can go back to the concentration of samples as shown in Figure  4C. Briefly, the concentration is calculated as (value + blank)/slope and normalized by dilution factor, sample volume, and fresh weight. Usually, the final level is normalized to provide a value with the units nmol/gFW, where gFW refers to the fresh weight of the plant material in grams.
Acknowledgments This work was supported by funding from the  Max-Planck Society  (Y. Z. and A. R. F. ), and A. R. F and Y. Z. would like to thank the  European Union 's  Horizon 2020 research and innovation program  and project  PlantaSYST  ( SGA-CSA  no  664621  and no 739582 under FPA no. 664620 ) for supporting their research. Y. G. acknowledges funding from  PHENOME  ( ANR-11-INBS-0012 ). Open access funding enabled and organized by Projekt DEAL.
Objectives of the FiberTAG Project We are developing innovative approaches to reconsider the nutritional advice and concepts concerning the health effects of prebiotic dietary fibre, namely by examining whether insoluble dietary fibre also functions as a prebiotic dietary fibre. In the context of the FiberTAG project, we are finalising a dedicated database detailing the soluble and insoluble dietary fibre and prebiotic (oligo)saccharide (ITF, FOS and GOS) content of food products consumed in Europe. In addition, we are building a food frequency questionnaire which focuses on all types of dietary fibre intake for use in intervention, retrospective or prospective studies. Moreover, there is a crucial need to develop and validate new biomarkers associated with the various health effects of dietary fibre, which take into account their interaction with the gut microbiota.
Conclusions The FiberTAG project is in the last phase of development and will end in 2021. Some preliminary data have recently been communicated in several key meetings. We hope, as a consortium, that the huge amount of data obtained from existing and new cohorts will bring new insights in the way we envisage the contribution of insoluble fibre to the modulation of the gut microbiota, and in the identification of adequate biomarkers linking dietary fibre intake, gut microbiota modulation (including co-metabolite production) and health outcomes.
Acknowledgement The  FiberTAG project consortium also includes Julie-Anne Nazare ,  Maud Alligier  and  Anne-Ester Breyton  from the  Centre de Recherche en Nutrition Humaine Rhône-Alpes  ( Univ-Lyon, France ),  Zhengxiao Zhang  from the  Department of Medecine (University of Alberta, Canada ),  Benjamin Seethaler  from  Institute of Nutritional Medicine (University of Hohenheim, Germany ),  Alexandra Meynier  from  Mondelez Int. R&D (France).
The DAD wavelength was set at 288 nm for VerA, 362 nm for AFB 1 and 329 nm for sterigmatocystin. Chromatographic data were monitored by Chromeleon® software (Thermo Electron Corporation, Waltham, MA, USA). Calibration curve was used for quantification with a linear model weighted by 1/x 2 (x = concentration) obtained from blank cell culture medium spiked with AFB 1 and VerA mixture at concentration ranging from 0. 1 to 10 µg/mL.
Cell cycle analysis HCT116 cells (100 × 10 3 ) or Caco-2 cells (50 × 10 3 ) were seeded in 24-well plates (Greiner Bio-One, Les Ulis, France) and treated with AFB 1 or VerA for 48 h. The cell cycle was investigated using the Click-iT EdU Alexa Fluor® 647 Flow Cytometry Assay kit (Sigma-Aldrich, Saint-Louis, MO, USA) according to the manufacturer's instructions. The cells were then washed and suspended in 0. 5 mL of PBS containing 4 µM 4′6′-diamidino-2-phenylindole (DAPI) at room temperature for 20 min. Fluorescence was recorded using a flow cytometer (MACSQuant Analyzer 10, Miltenyi Biotec, Bergisch Gladbach, Germany). The data were calculated using Venturi software (Applied Cytometry, Sheffield, UK).
Microarray analysis In order to evaluate the impact of VerA and AFB 1 on the global transcriptome, 1. 5 × 10 5 Caco-2 cells were seeded in six-well flat bottom plates and inoculated at 37 °C for 24 h. After incubation, the cells were treated with 1 µM VerA, 1 µM AFB 1 and DMSO for the control. After 24 h of incubation, mRNAs were extracted and processed for labeling and hybridized for Agilent SurePrint G3 Human GE 8x60K microarray (Agilent technology, Santa Clara, USA) as previously described  (Tannous et al. , 2017). All data and experimental details are available in the Gene Expression Omnibus (GEO) database under accession number GSE75934. Microarray data were analyzed with R software (R Core Team. , 2018), using the Bioconductor packages  (Huber et al. , 2015). The limma package  (Ritchie et al.
S3 ). The oxidative effect revealed by DNA Fpg-sensitive sites could be due to the formation of either 8-oxoguanine (as a consequence of ROS formation) or to the formation of an aflatoxin B 1 -formamidopyrimidine (AFB 1 -FAPY) adduct  (Smela et al. , 2002) , that can be recognized by Fpg enzyme  (Coste et al. , 2008). Due to its similar chemical structure to AFB 1 , VerA, could also lead to VerA-FAPY adducts, hence participating in the increase in DNA damage after Fpg treatment. These data confirmed that VerA exerts greater genotoxic stress in Caco-2 cells than AFB 1 , and that it is at least partly dependent on ROS formation. To further elucidate the consequences of the genotoxic activity of VerA and AFB 1 in Caco-2 cells, micronucleus formation was quantified. Only cells treated with 1 µM of VerA showed significantly more micronucleus than non-treated cells (Fig.
Acknowledgments We would like to thank  Joelle Laffitte ,  Souria Tadrist  and  Adeline Saysset  for their excellent technical assistance and  Dr Bert Vogelstein  for providing the HCT116 cell lines. We are very grateful to  Dr Laurence Huc  for her valuable advices along this study. This research was funded by the  ANR (Agence Nationale de la Recherche)  under Grant  ANR-11-ALID-0003  AFLAFREE and by  CAPES-COFECUB (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Comité Français d'Evaluation de la Coopération Universitaire et scientifique avec le Brésil)  under grant  SV 947/19. We also thank  Mrs Daphne Goodfellow  for her editing of this document.
FUNDING We acknowledge funding support from the Inserm Institute, the University of Montpellier, the Agence Nationale pour la Recherche for support of the national infrastructure: "ECELLFRANCE: Development of a national adult mesenchymal stem cell based therapy platform" (ANR-11-INSB-005). This study was also supported by a research grant called SEN-OA from FOREUM Foundation for Research in Rheumatology and the Arthritis R&D through the program "ROAD: Research on OsteoArthritis Diseases. ".
Background: The European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) was launched to register rare muscle glycogenoses in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases through workshops and websites. A network of twenty full and collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. After approximately 3 years of data collection, the data in the registry was analysed. Results: Of 282 patients with confirmed diagnoses of muscle glycogenosis, 269 had McArdle disease. New phenotypic features of McArdle disease were suggested, including a higher frequency (51. 4%) of fixed weakness than reported before, normal CK values in a minority of patients (6.
The EUROMAC project was funded by the European Union aiming to establish a network of clinical centres to develop the first European Registry for patients with McArdle Disease and very rare related muscle glycogenolytic disorders presenting with activity/ exercise intolerance as the key symptom  [5, 6]. The project was designed and built as described in the accompanying paper to this report  [7] , to raise awareness of diagnostic accuracy of muscle GSDs, improve the care, and collect important clinical and epidemiological data that can better describe the phenotypes and indicate endpoints for use in future clinical trials. This paper describes the data collected in the EUROMAC registry for patients with McArdle disease.
Methods The registry was designed under the guidance and consensus of EUROMAC members at specific meetings during the first months of the EUROMAC project. EUROMAC members were twenty full and collaborating partners from eight European countries (Denmark, France, Germany, Greece, Italy, Spain, Turkey and United Kingdom) and USA. The Netherlands and Poland joined the project later and contributed patients to the registry. The registry obtained the approval of all local Institutional review Boards for patient entry at the registry website (www. regis tryeu romac. eu). The project was divided into eight work packages (WP) to develop the registry (see Table  2  in accompanying paper)  [7]. The technical setup and data security for the registry are detailed in the accompanying paper  [7]. After review by people affected by GSDs and by a patient representative (WP2 -AGSD-UK) to ensure clarity  [8] , the participant information sheet and consent form were translated into languages of the participating countries and adapted to follow local regulations.
All patients consented in writing before inclusion in the registry. Any doctor working at a European institution was able to register on the EUROMAC platform and enter patient data. Inclusion criteria were patients with a diagnosis of one of the 14 known muscle GSDs either verified by the presence of two pathogenic mutations in the relevant genes (one pathogenic mutation for phosphorylase b kinase and phosphoglycerate kinase deficiencies as they are X-linked) or for McArdle disease and phosphofructokinase deficiency, lack of enzymatic staining on muscle biopsy. Patients with Pompe disease were excluded as there is a well-established registry for this disease already (https ://clini caltr ials. gov/ct2/show/NCT00 23140 0). Following informed consent from the participant, data were uploaded onto a safe, encrypted web-based registry.
Recruited participants were able to log in, review their own information and complete selected sections with their personal experiences. None of the recruited participants or participating doctors were allowed to see data from other patients. Data entry items are shown in Table  3  of the accompanying paper  [7]. Muscle strength was assessed by manual muscle testing in patients older than 18 years (n = 247) by a trained neuromuscular specialist. Data was only entered once, except if missing data was uploaded later. Data was based on clinical status and medical history at data entry.
Cardiorespiratory fitness (peak oxygen uptake [VO 2peak ]) A cycle ergometry exercise test was performed in 71 patients in Spain (n = 41), Italy (n = 14), United Kingdom (n = 9) and Denmark (n = 7); one exercise test was excluded from data analysis as the cycle test was interrupted prematurely. The median VO 2peak was 18. 5 ml/ kg/min. This value is a little less than half that expected in matched healthy people. The lowest result was seen in a 48-year-old woman with fixed muscle weakness.
Comorbidities In this cohort, 80 people (33. 2%) did not have any comorbidity (median age: 34 years). Recorded comorbidities are shown in Table  6. Median age of patients with comorbidities was 50 years. Hypothyroidism affected men (n = 7) and women (n = 7) equally (age range at data entry: 17 -77 years; median age: 59. 5 years; mean age: 52. 5 years). The two thyroid gland tumors reported were a benign adenoma and a malignant carcinoma. Pathogenic variants are listed according to their frequency. Numbers in columns below the headings "heterozygous" and "homozygous" show number of persons carrying the pathogenic variant in a compound heterozygous or homozygous state. Pathogenic variants that are in italic are novel pathogenic variants not present in Human Gene Mutation Database. θ signifies frameshift pathogenic variants where the nucleotide change is unavailable.
Conclusions The EUROMAC project and international registry have significantly raised awareness of McArdle disease, and should inspire opinion leaders in other fields to develop similar patient registries. The analysis of the registry data has given insight into new phenotypic features of McArdle disease and the variety of co-comorbidities affecting people with McArdle disease, which should lead to strategies reducing and managing these in the future, including controlling weight, and preventive screening for thyroid and coronary artery diseases. The data of the registry suggest that physical examination should focus more on occurrence of ptosis and fixed muscle weakness, which may be overlooked, and stresses the need not to discard a diagnosis of McArdle disease even though CK is normal and episodes of myoglobinuria are absent.
Acknowledgements EUROMAC was supported by several patients' associations and large networks of patient registries, such as the  Association for Glycogen Storage Disease  (https ://agsd. org. uk/) and the  EPIRARE Group on Rare Disease Registries  (https ://www. eurordis. org/conte nt/epira re). The  European Neuromuscular Centre  (https ://www. enmc. org/)also supported the project by contributing to the organization and funding of a dedicated workshop. EUROMAC Consortium:  Antoni L. Andreu ,  Ramon Martí ,  Tomàs Pinós ,  Noemi Baruch ,  Francisco J. Ortega ,  Miguel A. Martín ,  Carmen Navarro ,  Beatriz San Millán ,  Irene Vieitez ,  Andrea Martinuzzi ,  Monica Castelli ,  Federica Zucchi ,  Claudio Bruno ,  Antonio Toscano ,  Olimpia Musumeci ,  Pascal Laforêt ,  Sabrina Sacconi ,  Ros Quinlivan ,  Renata Scalco ,  Andrew Wakelin ,  Georgios Hadjgeorgiou ,  Elias Zintzaras ,  John Vissing ,  Matthias Vorgerd ,  Enrico Zülow ,  Ronald Haller ,  Piraye Oflazer ,  Hacer Durmus ,  Jean Pouget ,  Alejandro Lucia ,  Alfredo Santalla.
20 Genomic scans were carried out to detect the genomic signature of selection between landraces, between the five geographic groups and between landraces and inbred lines using two approaches: (i) the detection of 1 Mbp regions that were outliers for FST, referred to as "Outlier FST analysis" (ii) the detection of loci under selection using the drift model implemented in the BAYESCAN software (84) (Supplementary Information 4).
Acknowledgements This study was funded by the"  Association pour l'étude et l'amélioration du maïs" (PROmais)  within the " Diversity Zea " project and the  French National Research Agencies  with thein " Investissement d'Avenir Amaizing "  project , ( ANR-10-BTBR-01 ). We greatly acknowledge the  French Maize Biological Ressource Center, PROmais , and the  INRAE experimental units of St Martin de Hinx and Mauguio  for collecting and maintaining the collection of landraces and inbred lines. We greatly acknowledge colleagues who initially collected these landraces and  André Gallais  for initiating these research programs. We also greatly acknowledge  Pierre Dubreuil ,  Letizia Camus-Kulandaivelu ,  Cecile Rebourg ,  Céline Mir ,  Domenica Maniccaci  who conducted previous studies on these landraces using the DNA pooling approach with SSR and RFLP markers.
Data availability Fluorescence Intensity Data from 166 DNA samples of landraces used for predicting allelic frequency and modified Roger's distance matrix are available at https://doi. org/10. 15454/D4JTKB. To predict allelic frequency in 166 DNA pools, we calibrated our two-step model with fluorescence intensity data of 327 inbred lines (for calibrating the fixation test) and two series of controlled pools (for calibrating logistic regression) with R script that are available at the following address: https://doi. org/10. 15454/GANJ7J. Note that data will be available at the two web links below upon the publication will have been accepted in a journal.
We applied this framework to a simplified geometry which is assumed to represent a femur diaphysis under simple tension. Since we assume a constant distribution of the stresses through the thickness of the femur diaphysis, we propose to study a simplified 2D rectangular beam of length L ¼ 50mm and height H ¼ 20mm. The materials parameters are defined by the Young modulus of the cortical bone E ¼ 20 GPa and Poisson ratio ¼ 0. 3. The applied mechanical load is equivalent to a human body weight F ¼ 400 N and an initial bone density is taken as q ini bone ¼ 0. 5. Several scenarios were studied corresponding to different values of the external force. The model was implemented within the Software Comsol Multiphysics.
The access to Gaussian rigidity that this assay provides could advance the study of its role in complex domain formation processes in vivo. The work of LG, PF was supported by the VIDI grant scheme of the Netherlands Organisation for Scientific Research (NWO/OCW). PF would like to thank the IAS and the University of Warwick for their support and hospitality during the completion of this project. SCAI acknowledges funding from the UK EPSRC under grant number EP/L015374/1 (Centre for Doctoral.