dataesr/scientific-paragraphs-categorization huggingface dataset:
Most clinical guidelines can only be defined due to the gathering of expert opinions which is considered the lowest possible level of evidence, but is still much better that nothing. The Orphanet database provides access to 100 clinical guidelines covering 470 rare diseases, a very low number indeed. They were produced either by learned societies, charities, by disease-specific consortiums, or HTA agencies. They are very costly to produce due to the intensity and complicated nature of the process that has to be respected. They have to ensure that they not only reflect the gathered evidence, but also fit within the healthcare systems as they define healthcare pathways. It is the reason why only a few of them can be considered to be "International" clinical guidelines, most of them being quite specific to a country or a region.
OJRD is inviting funders to support the development of clinical guidelines and will support their publication. For some rare diseases it is also indispensable to provide emergency guidelines for pre-hospital emergency care as well as for hospital emergency care, as some interventions can be decisive, negatively or positively, in the recovery of the patient. These are even more difficult to produce and translate into recommendations which can be widely applicable. Currently the Orphanet database gives access to 44 emergency guidelines for 85 rare diseases (http://www. orpha. net/consor/cgi-bin/ Disease_Emergency. php?lng=EN). They were produced by French reference centres and patient organisations, edited by Orphanet, peer-reviewed by emergency practitioners, and then translated into English.
Patients suffering from a rare disease are more likely to need inpatient care, surgery and anaesthesia. Perioperative complications may occur in this setting, especially if the medical team lacks specific knowledge of the disease. Reliable information on orphan diseases is essential to avoid preventable diseaserelated complications such as unexpectedly difficult intubations, electrolytic imbalances, or adverse reactions or interactions of medication. The German Society of Anaesthesiology and Intensive Care developed OrphanAnaesthesia, (http://www. orphananesthesia. eu/ en/home. html) an anaesthesiology-related database on orphan diseases which now contains over 30 guidelines published in German and English (written and peer reviewed by experts). Projects like these need more volunteers to contribute towards the production of potentially life-saving recommendations.
Animals and phenotypes Data were collected from the French progeny-testing programs for artificial insemination (AI) using bulls from the Blonde d' Aquitaine and Limousin breeds. Three traits that are linked to maternal care were recorded on 2284 purebred females that were born between 2002 and 2011 and were the daughters of 70 Blonde d' Aquitaine sires and 57 Limousin sires. The number of records, raw means and raw variances for each trait are in Table  1. The udder score (US) that assesses udder swelling was scored 1 week before calving according to a five-point scale ranging from 1 for the least swollen udder to 5 for the most swollen udder (see Additional file 1). Maternal behavior (MB) was scored during the first hour after parturition and it aimed at describing the intensity of the dam's protective behavior towards her calf.
Genotypes In total, 2269 females (1259 Limousin and 1010 Blonde d' Aquitaine cows) were genotyped. Most of the females were genotyped using the customized low-density chip EuroG10K BeadChip ®. Only 249 Blonde d' Aquitaine cows were genotyped with the Bovine SNP50 BeadChip ® [medium-density (MD) chip]. Most of the sires (69 of 78 Blonde d' Aquitaine and 39 of 57 Limousin sires) were genotyped using the Bovine HD BeadChip ® corresponding to a high-density (HD) chip with 777K single nucleotide polymorphisms (SNPs). The remaining sires were genotyped with the MD chip. All female genotypes were imputed to HD by applying a two-step procedure, from low-density to MD, then from MD to HD, using the BEA-GLE 3. 3. 0 software  [9]. The procedures used for genotype editing and imputation are described in Hozé et al.
We used GS3 software  [18]  to perform these analyses. A total of 100,000 iterations were performed, with a burn-in of 20,000 iterations. The retained π value was equal to 0. 025 %, corresponding to 177 SNPs selected at each iteration among all the SNPs on the HD chip, in order to have a smaller number of SNP effects to estimate at each iteration than the number of phenotypic records. This value of π was sufficient to com- pletely capture the additive variance derived under the pedigree BLUP animal model. We verified that adding a polygenic component to the sum of the SNP effects in the model did not help to capture any spurious associations and did not modify the results of the pure genomic model. Therefore, a pure genomic model was retained to present the results.
However, our results on the within-breed detection of QTL strongly questioned this initial assumption. First, we found no common QTL for MB across the two breeds. Second, our results provided strong evidence (logBF > 8) for only one QTL for MY, which was shared by the two breeds. This QTL was located on chromosome 3 (Table  5 ) and explained only 16. 5 and 18. 5 % of the accuracy of genomic predictions for the Blonde d' Aquitaine and Limousin breeds, respectively. The peak SNP for MY in the Limousin dataset was located 0. 001 Mb upstream of the CASQ2 gene (Table  6 ). This gene encodes a calcium binding protein that stores calcium for muscle function  [49]. In dairy cows, Horst et al. [36]  demonstrated the relationship between calcium storage and MY, which makes CASQ2 a possible candidate gene.
Genotyping data for the Limousin breed did not allow us to clarify the very high genetic correlation between MY and US that was estimated based on performance and pedigree information. As a consequence, we assume that numerous pleiotropic regions with minor effects must explain the polygenic correlation, without any statistical possibility of detecting the corresponding QTL because of the limited size of our dataset. Nevertheless, we identified 15 candidate genes that could explain the major sources of additive genetic variation in maternal traits in continental beef breeds. Among these, four genes may have a role in the significant variations in suckling performance of both Limousin and Blonde d' Aquitaine cows. Future studies based on the analysis of sequence data for the highlighted regions may allow us to determine the causal mutations.
github. io/picard/) and GATK (v3. 5)  (McKenna et al. , 2010)  for indexing, sorting, removing PCR duplicates, and local-realignment. The per-based mapping depth was calculated by bedtools (v2. 25. 0) (Quinlan and Hall, 2010)  and the sliding window plots (window size = 100 bp, step size = 50 bp) were created by in-house Perl and R scripts. We also employed MACS (v1. 4. 2)  (Zhang et al. , 2008b)  to contrast each ChIP sample versus WCE sample for peak calling.
Acknowledgements We thank  Jun-ichi Nakayama  for providing chromo domain expression plasmids,  Matthieu Schapira  for G9a plasmid,  National BioResource Project (Japan)  for providing the genomic DNA library,  Charlie Hoffman  for the cDNA library, and members of  Jia lab  for helpful discussions and critical reading of the manuscript. This work was supported by  National Institutes of Health  grants  R01-GM085145  to SJ,  S10-OD012018  to LT, the  National Center for Research Resources  ( P41-RR011823 ), and  National Institute of General Medical Sciences  ( P41-GM103533 ). J-XY is supported by a postdoctoral fellowship from  Fondation ARC pour la Recherche sur le Cancer  (n  ˚PDF20150602803 ). This work is based upon research conducted at the  Northeastern Collaborative Access Team beamlines , which are funded by the  National Institute of General Medical Sciences  from the  National Institutes of Health  ( P41 GM103403 ).
Gas chromatography (GC) Essential oil sample analysis was performed on Perkin-Elmer Clarus 500 gas chromatograph (FID) equipped two fused silica capillary columns (50 m x 0. 22 mm, 0. 25 μm film thickness) BP-1 (polydimethylsiloxane) and BP-20 (polyethylene glycol). The oven temperature was programmed as follow: 60-220°C at 2°C/min and then held isothermal at 220°C for 20 min. The carrier gas was hydrogen, at a flow of 1. 0 mL/min; injector port and detector temperature were 250°C. Sample was injected by splitting and the split ratio was 1:60. The relative proportions of the oil constituents were expressed as percentages obtained by peak area normalisation, Retention indices (RI) were determined relative to the retention times of a series of n-alkanes (C7-C28) with linear interpolation ("Target Compounds" software from Perkin-Elmer).
C Nuclear magnetic resonance (NMR) 13 C NMR analyses (essential oil and CC fractions) were performed on a Bruker AVANCE 400 Fourier Transform spectrometer operating at 100. 623 MHz for 13 C, equipped with a 5 mm probe, in deuterated chloroform (CDCl 3 ), with all shifts referred to internal tetramethylsilane (TMS). 13 C NMR spectra were recorded with the following parameters: pulse width (PW), 4 µs (flip angle 45°); acquisition time, 2. 73 s for 128 K data table with a spectral width (SW) of 22 000 Hz (220 ppm); CPD mode decoupling; digital resolution 0. 183 Hz/pt. The number of accumulated scans was 3000 (50 mg of the mixture in 0. 5 mL of CDCl 3 ). Exponential line broadening multiplication (1. 0 Hz) of the free induction decay was applied before Fourier transformation. NMR spectra of essential oils and the two fractions of chromatography with those of reference spectra compiled in the laboratory spectral library, with the help of a laboratorymade software  (Tomi and Casanova 2006, Bighelli and Casanova 2009).
For Multicolor Competition Assay, control cells and fluorescent shRNA cells were counted, mixed with a 1:1 ratio, and were left untreated or treated either with CDT wt or CDT H153A. After 6 days of culture, cells were collected and the fluorescent rate was analyzed by flow cytometry with a Miltenyi MACSQuant Analyser 10 cytometer. Analysis was made with VenturyOne software (Applied Cytometry). Relative survival of shRNA-untreated cells was set to 1.
H2AX antibody was purchased from Epitomics (3522-1), γ H2AX antibody from Merck/Millipore (05-636), ATR (SAB4200348), Lamin A/C (SAB4200236), β -actin (sc-47778) antibodies from Santa Cruz, XRCC1 (X0629), XRCC4 (HPA006801), XPA (SAB1406599-50UG) antibodies from SIGMA, FANCD2 (NB100-182) antibody from Novus Biologicals, and GAPDH (GTX100118) antibody from GeneTex. Secondary fluorescent antibodies (CF TM 770.
Acknowledgements We are grateful to  Dr Patrick Calsou  for AA8, EM9 and MEF cells,  Dr. Jean-Yves Masson  for  PD20  and  PD20 D2  cells. We thank  Pfizer  for the gift of calicheamicin-γ 1,  Pr Eric Oswald ,  Dr Jean-Philippe Nougayrède  and  Dr Frédéric Taieb  for their help with the E. coli CDT-I purification. We also thank the members of the  3R-Toulouse group  for fruitful discussions and  James Grey  for his help with the manuscript. This work was supported by an  Agence Nationale de la Recherche  ( ANR) program  to GM (Grant number  ANR-10-CESA-011 ) and by the Institut.
For experiments, slices were perfused (2-3 ml/min) at 31°C with oxygenated ACSF. Neurons were patched at 40x magnification using an upright microscope (Zeiss Axioscop FS2+). Patch-clamp recording pipettes (4-5 MΩ) were filled with intracellular solution (in mM): 140 K-gluconate, 10 HEPES, 4 ATP, 2 MgCl2, 0. 4 GTP and 0. 5 EGTA (adjusted to pH 7. 3 with KOH, 280-290 mOsm. kg -  ). Stable whole-cell voltage-clamp recordings were obtained from layer 5 pyramidal neurons (L5PyNs, identified by the shape of their soma and main apical dendrite and from their firing profile induced by 1s depolarizing steps ranging from 0 to 200 pA) with a Multiclamp 700A amplifier (Axon Instruments, USA). Data were sampled at 2 kHz using a Digidata 1322A acquisition board (Axon Instruments, USA). Voltage data were corrected off-line for a measured liquid junction potential of -10 mV.
Determination of the E-I balance Data were analysed off-line with Acquis1TM and ElphyTM (Biologic UNIC-CNRS, Gif-sur-Yvette, France). The E-I balance determination is based on the continuous measurement of conductance dynamics during the full-time course of the stimulus-evoked synaptic response. Briefly, we performed post-hoc decomposition of postsynaptic current waveforms in excitatory and inhibitory conductances together with continuous estimation of the apparent reversal potential of the composite responses. This allows a somatic measurement of the E-I balance in L5PyNs after dendritic integration of incoming excitation and inhibition  [27]. In order to extract the excitatory and inhibitory conductance changes from the evoked synaptic currents, the neuron is considered as the point-conductance model of a single-compartment cell, described by the following general membrane equation: Cm dVmðtÞ dt ¼ gleakðVmðtÞ À EleakÞ À gEðtÞðVmðtÞ À EexcÞ À gIðtÞðVmðtÞ À EinhÞ þ Iinj where Cm denotes the membrane capacitance, Iinj the injected current, gleak the leak conductance and Eleak the leak reversal potential.
Statistical analysis Data reported are mean ± standard error of the mean (SEM) of n cells. Each individual cell was recorded in a single acute slice (3-4 slices/ animal per day) in order to avoid repeated exposure to the TBS protocol and/or drug application. When a LTP protocol was applied (TBS), post-TBS conductance integral values were normalized to pre-TBS conductance integrals (100%) and expressed as percentage of baseline. LTP was defined as a change >130% of baseline 1 h post-TBS. Statistics were performed using the InVivoStat software (Mockett Media). Paired samples for IntgT, IntgE, IntgI, between the control condition (before TBS) and given times after TBS (15, 30, 45 or 60 min) were analyzed using the paired student t-test.
Immunohistochemistry Rats were deeply anesthetized with pentobarbital (6%) and perfused transcardially with phosphate buffer (PB) 0. 1 M (pH 7. 3) and paraformaldehyde (4%) supplemented with 0. 25% glutaraldehyde. The brain was post-fixed overnight in the same solution and finally cryoprotected with 30% sucrose in 0. 1M PB. Brains were sliced (30 μm) using a vibratome and immunostainings were performed as previously described  [13]. Immunostained sections were observed with a ZEISS LSM 710 confocal microscope (ZEN software) with 405 diode, 488 and 633 laser lines. All image acquisitions were achieved using 40X and 60X magnification and variable numerical zooms. Channels were acquired with sequential scanning with a pinhole aperture of 1 airy unit each. Images were then analyzed using ImageJ software.
Pharmacological inhibition of SR not only prevented the TBS-induced eLTP and iLTP as observed with RgDAAO (Fig  3B  & 3E ) but also induced depression of the synaptic responses, as observed with 7Cl-KYN (Fig  3B  & 3E ; IntgT: 75. 9 ± 7. 4% of baseline; IntgE: 77. 3 ± 7. 6% of baseline; IntgI: 75. 3 ± 8. 6% of baseline; n = 17 cells, 17 slices, 8 animals, Ps<0. 01). Altogether, the dataset therefore indicates that D-serine is required for both eLTP and iLTP and that its absence unmasks a depression of evoked synaptic responses recorded at the soma of L5PyNs.
Acknowledgments This research was supported by grants from  CNRS. CNJM received a studentship from  CNRS  and  SANOFI-AVENTIS RD Exploratory Unit. JPM and GD were supported by  Agence Nationale pour la Recherche  (Grant number  ANR-09-MNPS-022-01 ),  CNRS ,  Université Aix-Marseille  and  Fondation pour la Recherche Médicale  (to J-P. M. ). The authors are grateful to  Dr Cyril Monier  who wrote and provided support with the analysis software. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This research was supported by grants from the  Centre National pour la Recherche Scientifique (CNRS) ,  SANOFI-AVENTIS  and  Agence Nationale de la Recherche (ANR ). CNJM received a studentship from  CNRS  and  SANOFI-AVENTIS RD Exploratory Unit. JPM and GD were supported by  Agence Nationale pour la Recherche  (Grant number  ANR-09-MNPS-022-01 ),  CNRS ,  Université Aix-Marseille  and  Fondation pour la Recherche Médicale  (to J-P. M. ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. work of CNJM was funded by  Sanofi-Aventis. However, this does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Describing seed size and shape using traditional and geometric morphometrics Size analysis of seeds. Four parameters representing the seed dimensions were measured using ImageJ version 1. 42  [47]  (Fig  1 ). Length and width of seeds were measured on the dorsal view. Thickness was measured as the maximum width of the seed lateral side. The surface of the dorsal side of the seed was also measured. The correlations between each pair of size parameters were plotted and assessed using Pearson product-moment correlation tests. Fourier analysis of seed outlines. Seed shape was quantified using outline analyses based on Fourier method following the protocol developed on Phoenix seeds  [19, 48]  and implemented in R software (Momocs package  [49, 50] ). The x and y coordinates of 64 points equally spaced along the outline of each seed were extracted semi-automatically using an image analysis system, the starting-point being the seed base.
Acknowledgments Dr. Jean-Christophe Pintaud  passed away before the submission of the final version of this manuscript. This article is dedicated to our colleague and friend who died prematurely. We are immensely grateful to  Jean-Christophe Pintaud. Dr. Muriel Gros-Balthazard  accepts responsibility for the integrity and validity of the data collected and analyzed. We thank the  Royal Botanic Gardens , the  Millennium Seed Bank , and the  Carpological Collection, Kew (UK) ; the  Herbarium Palmarum , the seed reference collection and the  Centro Studi Erbario Tropicale, Firenze (Italy) ; the Montpellier herbarium of the  Institute of Botany, France ; the  Centre de Recherches sur l'Elevage et le Pâturage, Kébili, Tunisia ; the  Centre Régional de Recherches sur l'Agriculture d'Oasis (Ministry of Agriculture ), Degache, Tunisia; the  Research Department of the Ministry of Agriculture of Oman  who issued the permission of seed collection for this study.
We acknowledge  Susi Gomez  and  Michel Ferry ,  Phoenix station, Elche, Spain  and  Vincent Battesti ,  CNRS-MNHN, France. We are grateful to the many collaborators who gave us permission to collect seeds on their private lands. This work was supported by the  Agence Nationale de la Recherche  (http://www. agence-nationale-recherche. fr/): programme blanc ,  ANR-06-BLAN-0212-02 - PHOENIX  project (dir. M. Tengberg; WP coordinated by J. -F. Terral ) and  ANR-07-BLAN-003301  - FRUCTIMEDHIS  project (dir. A. Durand; WP coordinated by J. -F. Terral). This work was also supported by PhD fellowships from the  French Ministry of Research  granted to M. G. -B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This article is the ISEM contribution n°ISEM  2016-032.
This work was supported by the  Agence Nationale de la Recherche  (http://www. agencenationale-recherche. fr/): programme blanc ,  ANR-06-BLAN-0212-02 - PHOENIX  project (dir. M. Tengberg; WP coordinated by J. -F. Terral ) and  ANR-07-BLAN-003301  - FRUCTIMEDHIS  project (dir. A. Durand; WP coordinated by J. -F. Terral). This work was also supported by PhD fellowships from the  French Ministry of Research  granted to M. G. -B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Xenopus oocyte electrophysiology. Oocytes were removed from Xenopus laevis as previously described  34, 35. After nuclear injection of cDNAs coding for each wild-type or modified AMPAR subunits (each 50-80 pg) alone or with P2X2 (10-30 pg), oocytes were incubated in Barth's solution containing 1. 8 mM CaCl 2 and gentamycin (10 mg/ml, Sigma) at 19 °C for 1-3 days before electrophysiological recordings were performed as previously described  10. Two-electrode voltage-clamp recordings were conducted at room temperature using glass pipettes (tip resistance 1-2 MΩ) filled with 3 M KCl solution to ensure a reliable holding potential. Oocytes were voltage-clamped at -60 mV, and membrane currents were recorded with an OC-725B amplifier (Warner Instruments) and digitized at 1 kHz on a Power PC Macintosh G4 using Axograph X software (Axograph).
47 NA objective and an iXon3 EMCCD camera (ANDOR, Belfast, UK). Imaging was performed in an extracellular solution containing a reducing and oxygen scavenging system. For direct Stochastic Optical Reconstruction Microscopy, ensemble fluorescence of Alexa647 were first converted into a dark state using a 642 nm laser 30-50 kw/cm 2. Once the ensemble fluorescence was converted into a desired number of single molecules per frame, the laser power was reduced to 7-15 kw/cm 2 and imaged continuously at 50fps for 90,000 frames. Both the ensemble and single molecule fluorescence was collected by a combination of dichroic and emission filters (D101-R561 and F39-617, respectively, Chroma, USA) and a quad-band dichroic filter (Di01-R405/488/561/635, Semrock, USA). Super-resolution images were reconstructed using a Leica GSD analysis program and corrected for lateral drift using multicolor fluorescent microbeads (Tetraspeck, Invitrogen).
Acknowledgements We are grateful to  Dr. Katherine Roche  at the  NINDS, NIH (Bethesda)  for providing us with anti-phosphoSerine567 antibodies. Microscopy experiments were done at the  Bordeaux Imaging Center , a service unit of the  CNRS-INSERM and Bordeaux University , member of the national infrastructure France BioImaging. We thank  E. Verdier ,  N. Retailleau  and  C. Breillat  for their technical help. We also thank  E. Normand ,  F. Roguet  and  A. Le Bris  and for help with animal facility. This work was supported by the  CNRS, University of Bordeaux  and grants from the  Conseil Regional Aquitaine and Labex BRAIN   ANR-10-LABX-43. The Bordeaux Imaging Center is funded by  ANR-10-INSB-04.
Integrity of the events in soybean 305423 3 40-3-2 The genetic stability of the inserted DNA over multiple generations in the single soybean events 305423 and 40-3-2 was demonstrated previously (EFSA GMO Panel, 2010b, 2012a, 2013). Integrity of these events was demonstrated by Southern analyses. 6, 7 Additional real-time polymerase chain reaction data was provided demonstrating the presence of all the inserts deriving from soybean 305423 in the two-event stack. 7.
Information on the expression of the inserts 8 Plants were grown in 2005 (six locations, three replicate plots) and in 2011 (10 locations, four replicate plots) under field conditions in the USA and in Canada. 9, 10 The levels of GM-HRA and CP4 EPSPS proteins in the two-event stack soybean and the two single events were quantified by enzymelinked immunosorbent assay (ELISA). Protein levels were determined in leaves (V2, V5, R1 (only in 2011) and R3 stages), forage (R3 stage), roots (R3 stage) and in seeds (R8 stage). Data on seeds are  GM-HRA Donor organism: Glycine max. The full-length FAD2-1 protein is an omega-6 desaturase in soybean. Its expression is seed-specific and the enzyme is responsible for the synthesis of the polyunsaturated fatty acids found in soybean oil (Heppard et al. , 1996).