dataesr/scientific-paragraphs-categorization huggingface dataset:
About 20 participants were thus enrolled for each of the following experiments, except for Experiment 2, which was performed concurrently with a parallel experiment that required a larger sample size. The recruitment was made independently for each of the five experiments, but recruitments for Experiments 3 and 4 were made in parallel, and a few participants completed both experiments; those participants always performed Experiment 3 before Experiment 4. In no case were optional stopping procedures applied; the experiments ended either because the prespecified number of participants was reached or (in Experiment 2) because other experiments running in parallel stopped as well. Thus, the significance of the results was never considered as a criterion to stop or continue data collection. A summary of demographic information for each experiment is reported in.
Materials and apparatus We adapted the task designed by O'Connor,  Meade, Carter, Rossiter, and Hester (2014) , which was originally employed to test spatial sensitivity to reward, reported to be reduced in far relative to near space. In Experiments 1, 3, 4, and 5, participants wore a virtual-reality headset (Oculus Rift; https://www. oculus. com). The experiments were implemented within Unity (Version 5. 1. 2; Unity Technologies, San Francisco, CA) and Oculus Runtime (Version 0. 6; Facebook Technologies Ireland, Dublin, Ireland) software, which were used to create the virtual environment, display experimental stimuli on the head-mounted display, and record participants' responses. The experiments were run on a computer with an Intel Core i7 processor, AMD Fire Pro M6000 graphics card, and Windows 7 operating system.
The scene was rendered in Oculus Rift DK2 software, with a resolution of 960 × 1,080 per eye, a frequency of 75 Hz, and a field of view equal to 106°. In Experiment 2, participants faced a 15-in. screen at a distance of approximately 57 cm. The open-source software OpenSesame (http://osdoc. cogsci. nl/) was used to display experimental stimuli and record participants' responses. Stimuli were obtained with professional designing software (SolidWorks; Dassault Systèmes, Waltham, MA). The rendering of an empty room was designed to introduce depth cues by exploiting a Ponzo-like illusion. A very similar empty room was also created and presented as a virtual environment in  Experiments 1, 3, 4,  and 5. Across all experiments, we obtained different distance conditions by presenting red, green, or blue shapes (cubes or spheres) at different positions.
15 mV and 0. 4 mV). Stimulation frequency was set at 0. 1 Hz. Recordings were performed with an Axopatch-200B amplifier (Axon Instrument, Molecular Devices, Sunnyvale, CA). Data were low-pass filtered at 2 kHz, digitized (10 kHz, DigiData 1440A, Axon Instrument, Molecular Devices, Sunnyvale, CA), collected using Clampex 10. 2, and analyzed using Clampfit 10. 2 (Axon Instrument, Molecular Devices, Sunnyvale, CA). Both fEPSPs' area and amplitude were analyzed. Drugs. All drugs were added at final concentration to the superfusion medium (see Table  1  for details). Data Acquisition and Analysis. The magnitude of plasticity was calculated 40-44 min after the plasticity protocols as percentage of baseline responses. Statistical analysis of data was performed with GraphPad Prism (GraphPad Software Inc.
Behavioral Tests Motor coordination deficits was analyzed using the Rotarod and tightrope tests at baseline (ie, before MCAO), before treatment onset (ie, at 3 days after MCAO), and at weekly intervals after treatment onset. Spontaneous motor activity and anxiety were examined by open-field tests at 7 and 28 dpt and spatial memory assessed by Barnes maze tests at 8 to 19 dpt (for details, see Materials and Methods in the online-only Data Supplement).
Z1 inverted epifluorescence microscope equipped with Apotome optical sectioning by measuring cell numbers in 6 defined regions of interest of the striatum ipsilateral to the stroke (size, 500×500 µm; regions of interest centered 1. 5 and 2. 5 mm lateral to midline/2. 5, 3. 25, and 4. 0 mm below brain surface), as specified in Figure IE in the online-only Data Supplement. 8, 9 or cresyl violet and NeuN stainings, neuronal densities determined were multiplied with striatal areas of each section, thus correcting for consequences of brain atrophy. CD31 stainings were evaluated by counting microvessel numbers in the same regions of interest. Optical sectioning was used for correction of cell/capillary overcounts. Mean values were calculated for all regions of interest.
Immunohistochemistry for Biotinylated Dextran Amine Corticorubral plasticity was evaluated in 2 consecutive 40-µm-thick brain sections obtained from the level of the parvocellular red nucleus that were incubated with avidin-biotin-peroxidase complex and revealed by 3,3′-diaminobenzidine (DAB). Using an Olympus BX42 microscope, the number of tracer-stained fibers crossing a 500-µmlong intersection line on the brain midline were quantified. 8, 9, 11 These fibers originate from the contralesional pyramidal tract and innervate the ipsilesional red nucleus. The number of fibers counted was divided by the total number of labeled fibers that was evaluated in the pyramidal tract and multiplied with 100, resulting in percent values of fibers crossing the midline (Materials and Methods in the online-only Data Supplement).
ELISA In homogenates of peri-infarct striatum and cortex and homologous contralesional striatum and cortex, levels of BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), VEGF (vascular endothelial growth factor), and basic FGF (fibroblast growth factor) were determined using commercial kits (Materials and Methods in the online-only Data Supplement).
Postacute Delivery of S44819 Improves Poststroke Motor Coordination Recovery and Spatial Memory Body weight and laser Doppler flow above the core of the middle cerebral artery territory did not differ between animals treated with vehicle or S44819 (3 or 10 mg/kg), neither in the exploratory study (Figure IIA and IIB in the online-only Data Supplement) nor in the confirmation study (Figure  IIIA  and IIIB in the online-only Data Supplement) nor when both studies were evaluated in a combined analysis (Figure  1A  and 1B ). In all groups, laser Doppler flow decreased to ≈15% of baseline during MCAO, followed by a rapid blood flow recovery after reperfusion. Motor coordination performance, assessed by Rotarod and tightrope tests, was markedly impaired 3 days poststroke, before the start of treatment.
S44819 Enhances NPC Proliferation and Neuronal Differentiation in the Ipsilesional Subventricular Zone To test whether the enhanced peri-infarct brain remodeling was associated with increased neurogenesis, we next assessed NPC proliferation and differentiation by BrdU incorporation analysis  in animals, in which BrdU had been administered at 3 defined time intervals, that is, from 3 to 8, 8 to 13, or 13 to 18 dpt. Compared with vehicle-treated animals, enhanced cell proliferation was observed adjacent to the ipsilesional subventricular zone (Figure  4A ) but not in the perilesional striatum (Figure VIA in the online-only Data Supplement) or the peri-infarct cortex (not shown) of animals treated with 3 or 10 mg/kg S44819, in which BrdU had been delivered at 13 to 18 dpt. Similarly, NPC differentiation, examined by BrdU colabeling with the immature neuronal marker DCX, but not NPC differentiation, assessed by BrdU colabeling with the mature neuronal marker NeuN, was significantly increased adjacent to the ipsilesional subventricular zone (Figure  4B  and 4C ) but not in the peri-infarct striatum (Figure  VIB  and VIC in the online-only Data Supplement) or the periinfarct cortex (not shown) of animals, in which BrdU had been delivered at 8 to 13 or 13 to 18 dpt.
Contralesional pyramidal tract plasticity, evaluated by anterograde tract tracing at the level of the red nucleus, was not influenced by S44819. Concentrations of neurotrophic growth factors (BDNF and GDNF) and angiogenic growth factors (VEGF and FGF) were increased in peri-infarct but not contralesional brain tissue. Our data reveal a profound restorative response in the peri-infarct brain tissue that prevents neurodegeneration and enables neurological recovery (visual overview). In models of permanent MCAO, that is, photothrombotic stroke in mice and cortical endothelin microinjection in rats, improvement of neurological deficits has repeatedly and consistently been reported after delayed subcutaneous or intraperitoneal delivery of the negative allosteric GABA A modulator L655708  3, 4  , which similarly to S44819 reverses tonic GABAergic inhibition.
Acknowledgments Drs Hermann ,  Bassetti , and Machado designed the study. Dr Wang performed the animal experiments, assisted by  Drs Sanchez-Mendoza  and  Silva de Carvalho. Drs Wang ,  Dzyubenko, Sardari , and  Doeppner  and  B. Kaltwasser  conducted histochemical/molecular biological studies. Drs Hermann  and  Kleinschnitz  provided infrastructural support. Drs Wang ,  Dzyubenko, Sardari , and Hermann analyzed the data. Drs Wang  and  Hermann  drafted the manuscript. All authors finalized it.
Patients, treatment and clinical variables The Otoplat protocol was approved by the Ethics Committee of Ile de France III (ClinicalTrials. gov. Identifier: NCT02425397). In this retrospective study, which started in March 2011 and ended in January 2016, we examined medical records of children treated with cisplatin and/or carboplatin in 10 French pediatric cancer departments: Curie Institute (Paris), University Hospital of Nancy, University Hospital of Nantes, University Hospital of Strasbourg, Institute of Pediatric Hemato-Oncology (Lyon), Gustave Roussy Institute (Villejuif), Trousseau Hospital (Paris), Oscar Lambret Center (Lille), Children Hospital (Toulouse) and Timone Hospital (Marseilles). We screened patients with pure tone audiometry performed in a sound-proof room, using visual reinforcement audiometry in youngest children.
q-PCR were performed in 25 μl on 35. 5 ng of DNA using TaqMan ® Universal Master Mix II, with UNG, on an Applied biosystem 7500 Real Time PCR system (Applied Biosystems). The thermal cycling comprised a holding stage (10 minutes at 95°C) and 45 cycles of denaturation (15 seconds at 92°C) and annealing/ extension (1 minute at 60°C). Analysis was performed on the Sequence Software (SDSv2. 0, Applied Biosystems). Genotypes were determined by an endpoint fluorescence reading.
Statistical analysis Statistical analysis was performed with ad hoc routines implemented in R software (http://www. R-project. org). The data are presented as proportions for categorical data and as median, interquartile range (IQR) and range for quantitative data. The primary endpoint was defined as moderate or severe hearing loss after the end of treatment (with a grade ≥2 on the Brock scale). Quantitative variables were compared with the non-parametric Wilcoxon tests and proportions with the Fisher's exact tests or the chi-squared tests, as appropriate. Logistic regression models were used to test all possible genetic inheritance models (i. e. , additive, dominant, and recessive) for all selected polymorphisms. GSTM1, GSTM3 and GSTT1 polymorphisms were analyzed as categorical covariate to evaluate the association between these gene deletions and hearing loss.
ACKNOWLEDGMENTS This study was funded by the  Fédération Enfants et Santé , was supported by the  Société Française de lutte contre les Cancers et les Leucémies de l'Enfant et l'Adolescent. We thank all the patients, participant centers,  Sandra Larrède  and  Adèle Bellino  from the  Clinical Research Department of Paris Descartes Necker Cochin , for their work.
pTyr and Nlg1/2/3 immunoblots are shown, respectively. g Average pTyr signals for the different inhibitors, normalized to the control, untreated condition (number of experiments within bars). h CA1 neurons from Nlg1 KO slices were electroporated with Nlg1-WT or Nlg1-Y782A, and AMPAR-mediated EPSCs were recorded upon stimulation of Schaffer's collaterals, in comparison to unelectroporated neighboring neurons (black traces). Organotypic cultures were treated or not with 1 µM GNF5837 for 7 days before the recordings. i Average AMPAR-mediated EPSCs amplitude in the 3 conditions, normalized to non-electroporated controls (number of pairs indicated within the bars, from 3 independent experiments). Data in graphs d and g were compared by one-way ANOVA followed by Bonferroni post hoc test (ns: not significant, *P < 0.
Nrx1β-Fc was then immunostained using a goat anti-human Fc (Jackson Immunoresearch, 1:400) followed by a Alexa568-conjugated donkey antigoat (Molecular Probes, 1:800). Coverslips were mounted in Mowiol (Calbiochem). Immunostainings in primary cultures were visualized on an inverted epifluorescence microscope (Nikon Eclipse TiE) equipped with a 60 × /1. 40 NA objective and filter sets for EGFP (Excitation: FF01-472/30; Dichroic: FF-495Di02; Emission: FF01-525/30); Alexa568 (Excitation: FF01-543/22; Dichroic: FF-562Di02; Emission: FF01-593/40); and Alexa647 (Excitation: FF02-628/40; Dichroic: FF-660Di02; Emission: FF01-692/40) (SemROCK). Images were acquired with an sCMOS camera (Hamamatsu ORCA Flash 4. 0), using the Metamorph® software (Molecular Devices). Detection of Nlg1 clusters was carried out after segmenting the Nlg1 signal using an automatic program written in Metamorph.
Laser powers were controlled through acousto-optical tunable filters driven by Metamorph. Atto594 was excited with the 561-nm laser line through a four-band beam splitter (R405/488/561/635, SemRock). Samples were imaged by oblique laser illumination, allowing the excitation of individual Atto-conjugated ligands bound to the cell surface, without illuminating ligands in solution. Fluorescence was collected using a FF01-617/73 nm emission filter (SemRock) placed on a filter wheel (Sutter Instruments). Stacks of 2000 consecutive frames were obtained from each cell, with an integration time of 20-50 ms. Image stacks were analyzed using a custom program running on Metamorph based on wavelet segmentation for localization and simulated annealing algorithms for tracking, described earlier  66. The program allows detection and tracking of localized single molecules through successive images.
Acknowledgements We acknowledge  A. M. Craig ,  F. Duschene ,  F. Janneteau ,  S. Okabe ,  P. Scheiffele ,  A. Ting , and  A. Triller  for the generous gift of plasmids,  N. Brose  for the gift of Nlg1 KO mice and Nlg3 plasmid,  D. Choquet  and  C. Breillat  for the anti-GluA1 antibody,  C. Poujol  and  S. Marais  at the  Bordeaux Imaging Center  for support in microscopy and image analysis, the animal facility of the  University of Bordeaux  (in particular A. Lacquemant), the cell culture facility of the Institute (especially  S. Benquet ,  P. Durand  and  E. Verdier ),  J. Carrere  and  R. Sterling  for technical assistance. The western blot analysis and recombinant protein production were done in the  Biochemistry and Biophysics Platform of the Bordeaux Neurocampus at the Bordeaux University  with the help of  J.
M. Blanc. We thank  A. Favereaux  and  V. Meriel  for the quantification of Nlg1 splice variants relative expression in primary hippocampal cultures through qRT-PCR and  J. Savas  for sharing proteomics data. This work received funding from the  Centre National de la Recherche Scientifique, Agence Nationale pour la Recherche  (grants  « SynAdh  »  ANR-13-BSV4-0005-01 ,  « SynSpe  »  ANR-13-PDOC-0012-01 , and  « Synthesyn  »  ANR-17-CE16-0028-01 ),  Commission Franco-Américaine  ( Fulbright program ),  Conseil Régional Aquitaine  (« SiMoDyn »),  Investissements d'Avenir Labex BRAIN   ANR-10-LABX-43  (« Synopto-genesis »), and  Fondation pour la Recherche Médicale  (« Equipe FRM »  DEQ20160334916 ), and the  national infrastructure France BioImaging  (grant  ANR-10INBS-04-01 ).
Plasmid transfections were performed using Effectene (Qiagen) following manufacturer instructions. pMTGal4-GFP, pUAST-Luciferase-Luciferase 3ЈUTR, pUAST-Luciferase-Repo 3ЈUTR, pUAST-Luciferase-Repo 3ЈUTR ⌬miR-1, and pTK-Renilla were all used at 20 ng/ml; and pTub-miR-1 was used at 50 ng/ml. The cells were cultured 2 d prior to induction with 500 M copper sulfate. The luciferase assay was performed 18 h after induction, using the Dual-Glo Luciferase assay kit (Promega) according to manufacturer instructions. Three independent transfections were averaged with SD. Statistical significance was calculated with GraphPad Prism software (GraphPad Software; RRID:SCR_002798) using a t test. RNA extraction, reverse transcription, and quantitative PCR. Total RNA was purified from stage 5-11 embryos using Tri Reagent (MRC).
One microgram of purified RNA was reverse transcribed by SuperScript II reverse transcriptase (Invitrogen) using oligodT primers (5 M). mRNAs were analyzed by quantitative PCR (qPCR) using Sybr Green (Roche) Master Mix, the thermocycler LightCycler480 (Roche) and the following oligonucleotides: repo: forward, 5Ј AAGCAGCAGCAAGAAGAAGG 3Ј; reverse, 5Ј ATACGGAGCACGTTCAAAGG 3Ј; and actin5C: forward, 5Ј GCAGCAACTTCTTCGTCACA 3Ј; reverse, 5Ј CTTAGCTCAGCCT CGCCACT 3Ј, For each gene, the mRNA levels were automatically calculated (LightCycler480 Software, release 1. 5. 0) by calibration to genespecific standard curves generated on input cDNAs. Collected values, derived from three amplification reactions, each performed in three independent experiments, were normalized to actin5C mRNA amounts. Statistics.
(ARC)   and  Agence Nationale de la Recherche (ANR)  grants. P. B. C. was funded by the  ANR  and by the  ARSEP  ( Fondation pour l'Aide ala Recherche sur la Sclerose en Plaques ), and G. T. by governmental and  ARC  fellowships. This work was also supported by grants from the  Ataxia UK  ( 2491 ) and the  NC3R (NC/L000199/1 ) awarded to M. F. The  Institut de Genetique et de Biologie Moleculaire et Cellulaire  was also supported by a  French state fund  through the  ANR  labex. D. E. S. was funded by  Marie Curie  Grant  CIG 334077/IRTIM. We.
Data analysis Reading performance and eye movement analyses were performed using the MeyeAnalysis software, which automatically determined the onset and end of each saccade by using a builtin saccade detection algorithm. The onset and end of each saccade identified by the algorithm was visually inspected and verified by the investigator. Initially, the total reading time (s) was obtained. This corresponded to the elapsed time from the first/last eye movement used to initiate/finish the reading task. Based on each saccade detection, the following variables were obtained: duration of fixation (the total time (ms) between two successive saccades); number of pro-and retro-saccades; and amplitude of saccades (in degrees). Postural control performance was evaluated using the surface area of the CoP.
RNA isolation and ELP1 splicing analysis Total RNA was extracted with TRIzol (ThermoFisher) following the manufacturer's instructions. Reverse-transcription was performed using 1 mg of total RNA and Superscript Vilo MasterMix (ThermoFisher). ELP1 minigene splicing was analyzed by endpoint PCR using specific primers, alpha 2, 3 F and ELP1EÂ21 R (Supplementary Material, Table  S1 ). PCR conditions were 94 C for 5 min, 40 cycles at 94 C for 30 s, 56 C for 30 s, 72 for 40 sfollowed by 72 C for 10 min. PCR products were analyzed by electrophoresis on a 2% agarose gel and the intensity of the bands was quantified with ImageJ Software (NIH). Endpoint PCR analysis of human ELP1 splicing was performed with human-specific ELP1 primers ELP1EÂ19 F and ELP1EÂ21 R. Quantitative PCR was performed with iQ-SYBR Green Supermix using human-specific ELP1 primers: ELP1FLF and ELP1FLR for the full-length ELP1 transcripts, ELP1D20F and ELP1D20 R for transcripts lacking the exon 20.
Electrophysiology: General Procedures BCs were identified as small-diameter cell bodies (∼10 µm) located in the internal third of the molecular layer. Recordings were performed at room temperature, ∼21 • C or at near-physiological temperatures, ∼34 • C as specified in the text, with HEKA EPC9 or EPC10 amplifiers and Patchmaster v2x32 software or with a Multiclamp700B amplifier (Axon Instruments) and a custom-made Igor-based program (FPulse, Dr. Fröbe, Institute of Physiology I, University of Freiburg 1 ). Electrophysiological data were analyzed with the help of Neuromatic (a collection of Igor Pro functions for analysis of electrophysiological data 2 ). Electrical coupling was detected by injecting a hyperpolarizing current pulse of 200-600 ms in one cell and recording the voltage change in the other cell.
Whole-Cell Recordings The internal recording solution contained: 144 mM K gluconate, 6 mM KCl, 4. 6 mM MgCl 2 , 2 mM CaCl 2 , 1 mM EGTA, 10 mM HEPES, 0. 4 mM Na 2 GTP, 4 mM Na 2 ATP; pH 7. 4; osmolarity: 295 mosm. Whole-cell recording pipettes had an open tip resistance from 6 MΩ to 9 MΩ. Junction potentials were taken into account in the presentation of whole-cell recording data by subtracting 12 mV from the values read from the amplifier. Experiments on coupled cells were performed in pairs with no direct chemical connections located at intersomatic distances smaller than 50 µm.
ACKNOWLEDGMENTS I am grateful to  Philippe Ascher ,  Thibault Collin ,  Isabel Llano ,  Alain Marty  and  Alberto Pereda  for support throughout the course of this study. I thank  Jin Bao ,  Michael Bennett ,  Claudio Elgueta ,  Mark Eyre ,  Ahmed El Hady ,  Lucy Palmer ,  Rebecca Piskorowski ,  Angus Silver  and  Michael Strüber  for useful comments on previous versions of this manuscript, and reviewers for their insightful comments. I thank  H. Monyer  for kindly providing Cx36-/-mice.
Study selection and data collection Individual participant data were sought from investigators of all prospective clinical studies identified through systematic searches of the published literature using MED-LINE and Web of Science databases (search terms "acute respiratory distress syndrome" and "receptor for advanced glycation end-products" up to March 2016) and by extensive discussions with the investigators (referred to herein as collaborators). Cohort studies, either interventional or observational, were eligible if the following variables were available in adult patients with ARDS: baseline plasma levels of sRAGE, baseline ΔP, tidal volume, and mortality at day 90. Data from each study were obtained using a standardized spreadsheet (appendix); raw data were examined, and inconsistencies or irregularities were clarified with the relevant investigators.
This study was exempt from institutional review board approval by the Clermont-Ferrand Sud-Est VI ethics committee because studies that were included were already published and had each previously received local institutional review board approvals and consent from participants. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participants Data (PRISMA-IPD) guidelines  [21]  (checklist available in the appendix). The protocol was registered on PROSPERO (ID: CRD42018100241) in June 2018. When available, data were collected on medical history and coexisting conditions (including diabetes,.
kg -1 of predicted body weight (PBW), inspiratory plateau pressure (Pplat), positive endexpiratory pressure (PEEP), and ΔP] and 90-day mortality was provided by collaborators in the greatest detail available. In all of the included studies, baseline levels of plasma sRAGE were measured in duplicate using commercially available enzyme-linked immunosorbent assays (R&D Systems, Minneapolis, MN, USA) at study entry. Apart from plasma sRAGE, all other data from randomized trials were collected after randomization. Prior to the transformation of the data from each study to a standard format for incorporation into a central database, the data were checked for consistency by a panel of investigators (RB, BP, JMC, and MJ), and any queries were referred back to the collaborators prior to the final harmonization of the data.