dataesr/scientific-paragraphs-categorization huggingface dataset:
Then, OE-MSCs cultured in serum-containing medium were trypsinised and resuspended in the serum-free medium. Every dish containing the agarose spots was seeded with 2 × 10 5 cells and then incubated for 24 h (37 °C in 5% CO 2 ). The number of cells invading underneath the agarose spot was manually counted using standard phase contrast light microscopy. Imaging was performed using an inverted phase microscope (TE300, Nikon) with a 10x objective, and images were acquired using an Orca-ER CCD camera (Hamamatsu Photonics) and Axiovision software (Zeiss). The total number of invading cells per agarose spot was counted, and the reported values are the mean number of cells per spot of at least three independent experiments. 2. 11. Statistics. All data are presented as mean ± SEM. Data were analyzed using SPSS/PC + statistics 11.
Lesioned Hippocampi Overexpress Genes Involved in Cell Chemoattraction. In order to find candidate OE-MSC chemoattractants within lesioned brain tissue, we established the gene expression profiles of control and lesioned hippocampi. Four weeks after the lesion, hippocampi were isolated and processed for pan-genomic microarray analysis (ArrayExpress database, accession number E-MEXP-2682). The data indicated that 114 transcripts with a fold change above 2. 5 were upregulated in the lesioned hippocampi. Interestingly, the DAVID Functional Annotation Clustering Tool showed that overexpressed transcripts clustered into functional groups, indicating in particular that 53% of these genes are involved in immune and inflammatory processes. More importantly, among the strongly upregulated transcripts (fold change above 10), four were coding for molecules already known for their chemotactic properties on immune cells and other stem cell types (Table  1 ).
CCL2 and SPP1 Stimulate OE-MSC Migration In Vitro. Our converging data led us to evaluate the effects of the human recombinant cytokines C3A, CCL2, SPP1, and CXCL10 on human OE-MSC migration. To this end, we used modified Boyden chambers and agarose spot assays to assess the chemotattractant potential of these molecules on OE-MSCs. Interestingly, only CCL2 and SPP1 stimulated OE-MSC migration in modified Boyden chambers. Indeed, we observed a significantly increased number of migrating cells in response to either of these two cytokines as early as 12 hours after treatment (Figures  5(a )-5(d)). Noticeably, our results showed a dose-dependent effect, starting to be significant when the concentration reached 400 ng/mL for both CCL2 (p < 0 01) and SPP1 (p < 0 001) (Figure  5 (d)), and no cumulative effect when both cytokines were used (Figure  5 (e)).
CCL2 Exerts a Chemotactic Effect on OE-MSCs In Vitro. In order to further elucidate CCL2 and SPP1 mechanisms of action on OE-MSC migration, we then evaluated the relative contribution of random cell motility (chemokinesis) and gradient-dependent cell migration (chemotaxis) of human OE-MSCs in response to CCL2 and SPP1. To distinguish chemotaxis from chemokinesis in modified Boyden chambers, we compared the effect of the cytokines placed either Microarray data indicate that 13 genes are overexpressed in lesioned hippocampi with a fold change above 10, one month after the lesion. All are known to be involved in immune and inflammatory processes and in tissue remodeling. Among these genes, 4 codes for cytokines with demonstrated chemotactic properties: C3, Ccl2, Spp1, and Cxcl10 (bold). in the lower well only or in both the upper and the lower compartments of the chamber, in order to disrupt the gradient.
Both datasets contained 119 common proteins while 510 were uniquely uncovered in our study. The sensitivity of the mass spectrometer used in our experiments may explain such a discrepancy. Nonetheless, both studies underline the importance of cell migration. Indeed, using Swiss-prot functional annotation, the previous study observed that the largest number of secreted proteins was associated to the cell growth and migration pathway  [41]. Similarly, we report here that 239 out of 629 OE-MSCsecreted proteins are associated to cell movement, migration, and/or homing. Neuroinflammation is a common denominator in damaged cerebral areas, and cytokines associated with neuroinflammation are known to be involved in the homing  mechanisms of different types of immune, tumor, and stem cells  [42]. Thus, deciphering the inflammatory processes in damaged areas is a prerequisite to understanding human OE-MSC homing mechanisms.
Acknowledgments The authors gratefully thank  Nathalie Baril  for her efficient help during MRI acquisition,  Nicolas Boulanger  and  Béatrice Loriod  for the microarray study (genomic platform TAGC, Ibisa, INSERM  U928 ),  Samuel Granjeaud  ( CRCM ) for his expertise in bioinformatics, and  Pascale Durbec  for her insight. This study was supported by  Fondation de l'Avenir, Stem Cells International French Institute for Spinal Cord and Brain Research (IRME) , and the  French National Research Agency (ANR)  ("ADHOC" project). They acknowledge the support from the  "Fonds Européen de Développement Régional" FEDER  in PACA region. Stéphane D. Girard ,  Isabelle Virard , and  Emmanuelle Lacassagne  were recipients of fellowships from  ANR , the  French Ministry of Research , and  IRME. The mass spectrometer was obtained using the financial support of the  "Fédération de Recherche pour le Cerveau" (FRC)  through the  Rotary operation "Espoir en tête.
A benchmark dose lower confidence limit for a 10% excess cancer risk (BMDL 10 ) of 70 lg/kg body weight (bw) per day was calculated as the reference point (RP) for comparison with the estimated dietary exposure. The CONTAM Panel concluded that there is a possible health concern for those toddlers and children who are high consumers of honey. It was furthermore concluded that, although no occurrence data were available, exposure to PAs from pollen, tea, herbal infusions and herbal dietary supplements could potentially present a risk of both acute and chronic effects in the consumer. Following the outcome of this scientific opinion from the CONTAM Panel on PAs in food and feed and the availability of new occurrence data on the presence of PAs in food, the Commission requested EFSA for a dietary exposure assessment to PAs in honey, tea, herbal infusions (herbs) and food supplements.
8-1. 7 mg PA/kg bw for 2 weeks and was diagnosed for HVOD, and a 2-month-old boy who was administered an approximate dose of 3 mg/kg bw for 4 days, with a fatal outcome. The dietary exposure assessment of the CONTAM Panel 2011 opinion was limited to honey as occurrence data were only available for this food product. Using occurrence data on 14 and 17 PAs from two independent data sets submitted to EFSA, with eight PAs in common between the two data sets, the CONTAM Panel estimated dietary exposure for the consumption of retail honey and for honey purchased locally from a single source. For retail honey, chronic exposure levels up to 37. 4 ng/kg bw per day and 9. 03 ng/kg bw per day were estimated for children and adults (mean consumption in honey consumers only), respectively. Chronic exposure up to 77.
The CONTAM Panel noted that MOEs calculated for all age groups when considering the maximum LB exposure levels are similar to respective MOEs at the maximum UB, indicating that the differences in consumption data present in the various surveys, rather than the analytical uncertainties in the occurrence data, are mainly responsible of the high variability observed in the minimum LB-maximum UB MOEs. When considering the 95th percentile exposure levels calculated in Scenario A, MOEs below 10,000 were calculated for all age groups both at the maximum LB and maximum UB. For the younger age classes MOEs ranged from > 10,000,000 to about 1,100 (min LB-max UB across dietary surveys and age classes), and for adults from > 200,000 to about 1,900 (min LB-max UB across dietary surveys and age classes).
The 95th percentile MOEs ranged from 395,000 to 1,500 and from 43,000 to 770 for the adult and young population, respectively. When looking at specific types of infusions, lower MOEs were calculated for the consumption of camomile flowers in particular in the young population (minimum LB-maximum UB approximately at 28,200-5,300 for mean consumption, 95th percentile not calculated), and for rooibos leaves both for adults (ranges of 21,500-5700 and 7,200-2,100 for mean and 95th percentile consumption, respectively) and the young population (range of 17,700-2,900, mean consumption, 95th percentile not calculated). A similar trend to the one reported in the scenarios on all consumers was observed when calculating MOEs for only consumers in Scenario B (data not shown). MOEs calculated for adult consumers only of retail honey ranged between > 1,000,000 and 32,000 (minimum LB-maximum UB) and between 593,000 and 13,500 for mean and 95th percentile consumption, respectively.
Uncertainty analysis Uncertainties associated to the estimates of dietary exposure to PAs have been already described  (EFSA, 2016). In brief, the main uncertainties refer the large proportion of left-censored data, the fact that not all samples reported analytical data for all 28 PAs, and to the presence of an important number of both eating occasions and occurrence data on unspecified tea and herbs for infusions. Likewise, there is uncertainty on how analytical methods (extraction) represent the different ways consumers prepare tea and herbal infusions. In addition, the fact that many other PAs, not routinely monitored or not yet identified, could also be present in food may lead to an underestimation of the exposure levels. Overall, the dietary exposure to PAs calculated was likely to overestimate the exposure levels of the European population.
C. Software used and specifications • Fitting benchmark dose models was based on the R-package proast61. 3. • Averaging results from multiple fitted benchmark dose models was based on the methodology in  Wheeler and Bailer (2008). • The default set of fitted models was applied as recommended by EFSA Scientific Committee (2017) • Selection of the BMD confidence interval and the BMDL was carried out following the flow chart of EFSA Scientific Committee (2017) Using the parametric bootstrap with a total of 1,000 generated data sets, the BMDL and the BMDU were the 5th and 95th percentile of all parametric bootstrap BMD values, respectively.
Data Collection Data on selected CBUs and their maternal characteristics were obtained from European Cord Blood Banks through a questionnaire on maternal and CBU characteristics. All participating Cord Blood Banks received the synopsis of the study, and 33 gave their consent (the list of participating Cord Blood Banks is in Acknowledgments). Data on patients, transplant procedures, and outcomes were cryopreserved from the electronic Eurocord database. All data were validated and checked by data managers and physicians in each European Group for Blood and Marrow Transplantation transplant center and Eurocord medical coordinator. The Institutional Review Board of Eurocord approved the study.
HLA compatibility was determined at the antigen level for HLA-A and HLA-B loci and at the allele level for the HLA-DRB1 locus. Cumulative incidence of neutrophil engraftment, NRM, and cGVHD were analyzed as the incidence rates and their 95% confidence intervals (CIs) to account for competing risks. Probabilities of OS and DFS were calculated using the Kaplan-Maier method, and the log-rank test was used for univariate comparisons. Multivariate analyses were performed using Cox proportional hazard regression model for DFS and OS and Fine and Gray's proportional hazard regression model for neutrophil engraftment, RI, NRM, and cGVHD. Because of the significant amount of missing data on date of onset of aGVHD, univariate analysis for factors associated with aGVHD was conducted using proportions, whereas logistic regression analysis was used for multivariate analysis.
ACKNOWLEDGMENTS The authors thank the following participating  Cord Blood Banks  for contribution to the cases:  Laura Ponce ,  Banco de Cordón de Málaga, Malaga, Spain ;  Cristiana Vaselli ,  Marina Buzzi ,  Emilia Romagna Cord Blood Bank , Immunohaematology and  Transfusion Medicine Service ,  S. Orsola-Malpighi Hospital ,  University of Bologna, Bologna, Italy ;  Zuzana Halasova  and  Maria Sanciova ,  Eurocord-Slovakia, Bratislava , Slovak.
AON Design ESE finder 3. 0 software 52 was used to determine the ESEs in E2 of hSOD1. This software can predict binding sites for the most abundant SR proteins (SF2/ASF, IgM-BRCA1, SC35, SRp40, and SRp55). The consensus sequence for the SA was identified in the first hSOD1 intron. Five RNA-based ASOs masking these sequences on hSOD1 pre-mRNA were rationally designed. The ASOs were designed following the specific rules published by Aartsma-Rus et al. 53  and using the RNAstructure 5. 3 software. Each ASO was designed to be 20 nt long and to have the highest melting temperature (Tm) and the highest binding energy between the ASO and the target E2 sequence. ASO 1: 5 0 -CCCACACCUUCACUG GUCCA-3 0 ; ASO 2: 5 0 -GGCCUUCAGUCAGUCCUUUA-3 0 ; ASO 3: 5 0 -CUGGUCCAUUACUUUCCUUU-3 0 ; ASO 4: 5 0 -CCAUGCAG GCCUUCAGUCAG-3 0 ; and ASO 5: 5 0 -CUGCUGUAUUAUCUCCA AAC-3 0.
Each sample was deposed in triplicate in a 96-well plate (Applied Biosystems). The thermal cycling conditions were: 1 min at 60 C and 10 min at 95 C, followed by 39 cycles of 15 s at 95 C and 1 min at 60 C in the StepOne Plus Real Time PCR System (Applied Biosystems). The relative quantity of hSOD1 mRNA was calculated using the delta Ct/delta Ct method, taking into account the PCR signal of the target gene transcript of each sample (normalized to the endogenous control) relative to that of the control sample. The qPCR analyses were performed with the StepOne software v2. 3 (Life Technologies).
0 software (Macintosh version, Adobe). Double immunofluorescence images were obtained by superimposing two or three single-color images of the same field. ChAT-positive motor neurons (with a diameter >20 mm) were manually counted in the ventral horn of the cervical, thoracic, and lumbar spinal cord segments using an epifluorescence microscope (Leica Camera AG). Astroglial activation was evaluated by measuring the fluorescence intensity of the GFAP staining in the gray matter of the spinal cords using ImageJ software. Microglial activation was evaluated by counting the Iba-1-positive cells in the gray matter of spinal cord sections. The myofiber area and number were quantified using ImageJ software. Fiber areas were calculated in square pixels and then converted into mm 2. Cell counting and morphological analyses were performed in a blinded manner.
20-mm-thick cryosections were serially cut from gastrocnemius muscles using a cryostat at À24 C and stored at À80 C. Sections were fixed with cold acetone, incubated with 594-conjugated BTX, and then processed for anti-NF immunofluorescence, as described above. Fluorescence images along the z axis were taken by a Leica SPE confocal microscope. Z stacks were done using ImageJ software, and images were processed as described above. Endplates were scored as innervated when BTX and NF signals co-localized and were scored as denervated if they showed only BTX staining. Endplate areas were measured using ImageJ software and were calculated in square pixels and then converted into mm 2.
Behavioral Analyses Body weight, strength, motor coordination, and spontaneous activity were assessed twice a week. The grip strength of the four limbs was evaluated using a grip strength meter (Bioseb) to determine the peak force (in grams) generated when the mouse is pulled back from a metal gird. For each test, five measures per animal were recorded. Motor coordination was assessed using an accelerating rotarod instrument (Bioseb), starting at 4 rpm/min. The time spent on the rotarod before falling was recorded in two runs per animal. At 17 weeks of age, the spontaneous activity of mice was assessed overnight (12 hr) using an actimeter to record the number of crossed infrared light beams, and data were analyzed using Track software (Bioseb). Survival was determined as the time when the mouse was unable to right itself in 30 s when placed on its side (defined as the end stage).
ACKNOWLEDGMENTS The authors sincerely thank  Bruno Cadot  ( Center of Research in Myology ) for his help in microscopy image acquisition,  Yannick Tanguy  for taking the mouse photographs and help in the statistical analyses,  Aurore Besse  for her technical assistance, and  Ilaria Di Emidio  for the illustrations. We also thank  G. Haase  and  M. Crescenzi  for critical reading of the manuscript. This work was funded by the  Association Française contre les Myopathies (AFM) , the  University Pierre et Marie Curie (UPMC) , the  Institut National de la Santé et de la Recherche Médicale (INSERM) , the  Centre National de la Recherche Scientifique (CNRS) , the  Association Institut de Myologie (AIM) , the  Otto per Mille Waldensian Church , and the  Association pour la Recherche sur la Sclérose Latérale Amyotrophique (ARSLA).
Sequencing was performed using 460-bp paired-end reads and an Illumina Miseq protocol on the GeT-PLaGe platform (Toulouse, France). Illumina reads were joined using the fastq-join method. The sequences were demultiplexed and quality filtered using the QIIME (version 1. 8. 0) software package. The sequences were assigned to OTUs using UCLUST algorithm 41 with a 97% threshold of pairwise identity and classified taxonomically using the Greengenes reference database.
impact of L. casei Bl23 Treatment on Microbiota richness and Diversity To determine the impact of L. casei BL23 on the gut microbiota, we analyzed microbiota richness and diversity after BL23 oral treatment. This analysis provided a total of 1,709,762 high-quality and classifiable reads, with an average of 5,000 (n = 51) reads per sample. First, beta diversity (Bray-Curtis distance) was analyzed in microbial samples using principal components analysis, which reduced the dimensionality of the data set. While no grouping was observed before AOM challenge (T0; Figure  6A ), the microbiota of mice treated with L. casei BL23 tended to diverge from those of PBS-treated animals at Tf (sacrifice; Figure  6B , p = 0. 1, Anosim). Then, we estimated community richness (alpha diversity; Shannon and Simpson indexes) at T0 and Tf.
Interpretation of reflux monitoring Data acquisition. Catheterbased ambulatory reflux monitoring (pH or pHimpedance studies) is performed over a 24 h period, with the distal oesophageal pH sensor positioned 5 cm proximal to the manometrically C O N S E N S U S S TAT E M E N T measured LES. Wireless pH probes are typically posi tioned 6 cm proximal to the squamocolumnar junction during EGD. These single sensor probes can record and transmit distal oesophageal pH data for up to 96 h and are better tolerated than ambulatory catheterbased testing  46. Catheter or probe placement is performed after an overnight fast and after withholding anti secretory therapy for at least 7 days when testing off PPI is performed. Patients are recommended to maintain normal activities and meals, and keep a diary of meals, symptoms, and recumbency periods  7, 10.
A cough detector can count and time cough events; this objective can also be achieved with ambula tory manometry. A simple ratio of associated symptoms to all symptoms defines the symptom index, which is abnormal if >50%  74. In addition, the number of symp toms should be reported for relevance, as the symptom index can be based on one event only. Symptom associ ation probability (SAP) takes into account 2 min periods with and without reflux episodes and symptom events, and applies a statistical test (Fisher's exact test) on a twobytwo table generated with this data  55. A P value <0. 05 (or SAP >95%) corresponds to a <5% chance that symptoms and reflux episodes could have cooccurred just by chance  55. A similar conclusion can be reached using the Ghillebert probability estimate, which utilizes posthoc statistical modelling from para meters routinely collected during a pH study to define symptom reflux association  75.
Acknowledgements The  International Working Group for Disorders of Gastrointestinal Motility and Function  initiated the consensus meetings and provided material support for the consensus process. Five separate groups reviewed the current state-ofthe-art in clinical measurement of gastrointestinal motility and function: oropharynx, esophagus, reflux disease, stomach / intestine and anorectum. This process was endorsed by the  European Society of Neurogastroenterology and Motility (ESNM)  and the  European Society of Colo-Proctology (ESCP)  with representation and support from the  American Neurogastroenterology and Motility Society (ANMS) ,  South and Latin American Neurogastroenterology and Motility Society (SLNG) ,  Asian Neurogastroenterology and Motility Association (ANMA)  and members of the  Australasian Neurogastroenterology and Motility Association (ANGMA).
Acquisition of diffusion MRI data Diffusion ex vivo data with high spatial and angular resolution were acquired to quantify the subtle changes in the WM microstructure within the entire rat brain. The ex vivo MRI acquisitions were performed on a 7 T preclinical scanner (PharmaScan, Bruker, Ettlingen, Germany) using a home-made quadrature birdcage coil (inside diameter = 28 mM). Diffusion images were acquired using a Spin-Echo Multi Shot Echo Planar Imaging (repetition time (TR) = 26 s, echo time (TE) = 29 ms, 90°excitation pulse followed by a 180°refocusing pulse, 4 segments, 4 averages, total time = 24 h16 m 03 s). One hundred four interleaved slices with 0. 25 mM thickness were acquired, with a matrix size of 106 × 106, a field-of-view of 25. 44 × 25. 44 mM and an in-plane resolution of 0.
Preprocessing of diffusion MRI The dMRI images were reconstructed using an in-house script and visually inspected for brain lesions and artefacts, after which two subjects (one F344 and one SD from the control group) were excluded because of the presence of artefacts. All the data were pre-processed using the FMRIB Software Library 41 (FSL, http://fsl. fmrib. ox. ac. uk/fsl/) v5. 0. 6 using the following steps: bias field correction using FAST,  42  correction of the field inhomogeneity, estimated from b0 images, on all volumes; eddy current distortions and movement correction with fsl 'eddy_correct' command-line tool (the first volume without diffusion sensitization was chosen as the reference volume for the affine registration); segmentation of the brain signal using BET:  43  BET was applied to the mean of the images without diffusion sensitization, with the resulting mask being applied to all volumes.
ACKNOWLEDGMENTS We thank  Neurospin (high field MRI center CEA Saclay)  for providing its support for MRI acquisition. JB was supported by grants from  Fondation pour la Recherche Médicale (FRM)  and  Groupe Pasteur Mutualité (GPM). This work was supported by a grant from  ANR (SIGMA). This work was performed on a platform of  France Life Imaging (FLI)  network partly funded by the grant  ANR-11-INBS-0006. This work and RM were supported by a fellowship of the project  FCT-ANR/NEU-OSD/0258/2012  founded by  FCT/MEC  (www. fct. pt) and by  Fundo Europeu de Desenvolvimento Regional (FEDER). AC was supported by a grant from the  Fondation NRJ.
, 2016). However, the Pathfinder and Phoenix landers were only operational for 85 and 152 sols respectively, and were not equipped with the necessary instrumentation to perform detailed studies of the near-surface water distribution. Additionally, the topography of Gale crater is likely to result in a more complex water cycle than that experienced by Phoenix in the northern plains. The Curiosity rover landed on the floor of Gale crater in late northern hemisphere summer (L S = 151 • ) of Mars Year (MY) 31. Since L S = 154 • , the Rover Environmental Monitoring Station (REMS) has been providing hourly measurements of, amongst other quantities, relative humidity, temperature and surface pressure  (Gómez-Elvira et al. , 2012 , 2014; Harri et al. , 2014a). This dataset, covering more than one Mars year, is ideal for investigating the regolith-atmosphere exchange of water.