dataesr/scientific-paragraphs-categorization huggingface dataset:
Patients Ten French centers included 502 patients in this prospective multicenter study evaluating the predictive value of RILA on the development of breast fibrosis (bf +). The National Ethical Committee approved this protocol and the study was registered in the NCI PDQ database (NCT00893035). The eligibility criteria included adult patients (age ≥ 18 years) with invasive breast cancer confirmed pathologically; breast-conserving surgery; negative surgical margins; T1/ T2 tumors; negative sentinel lymph node or negative/positive axillary node resection (pN -/pN +); negative/positive hormonal receptor tumor expression; post-surgery symptoms bgrade 2 (CTCAE v3. 0); patient affiliated to the French social security; dated and signed written informed consent. Exclusion criteria are presented in the protocol document.
Inclusion and Masking After obtaining informed consent, investigators provided by fax the necessary information to the data center in Montpellier. After an eligibility check, patients were included by the Biometrics Unit of Montpellier. The data center registered enrolment, assigned a unique sequential numbering for each patient, and answered by fax to the respective investigators. RILA was performed in the Montpellier radiobiology laboratory (Institut de Recherche en Cancérologie de Montpellier, IRCM, INSERM U1194, Montpellier, France) and results were concealed from the clinicians before final statistical analyses.
model of competing risks  (Fine, 2001)  for the assessment of the impact of RILA rate on the occurrence of bf+ in the presence of other events (such as relapse or death) that are considered as competing risk events in this pathology. For multivariate analysis, selected factors were the baseline parameters with a p value less than 0. 20 in univariate analysis. Final model was defined using backward stepwise selection (p b 0. 15) and a step by step method was used to include only the significant parameters (p b 0. 05). Data were summarized by frequency and percentage for categorical variables and by median and range for continuous variables. Absolute changes in RILA counts before and after irradiation were evaluated as continuous and categorical variables. Three categories were constructed around the 33% quantiles (b 12, 12-20, and ≥20) and then merged in two categories (b12 and ≥12).
, 1992)  and compared using Gray's test. Median follow-up was estimated with the inverse Kaplan-Meier method. A p value less than 0. 05 was regarded as significant. All statistical tests were two sided. Stata was used for all statistical analyses (version 13. 0) and the SAS macro %cif was used for Gray's test. To complement analysis, receiver-operator characteristic (ROC) curve analyses for RILA were performed to identify patients who experienced at least a grade 2 bf+ within three years  (Kramar et al. , 2001). The empirical areas under the ROC curves (AUC) and the respective 95%CI were used for RILA to determine the sensitivity, specificity, positive (PPV), and negative predictive value (NPV).
Trial Profile Fig. 1  shows the trial profile. From Jan 15 2007, to Jul 11 2011, 502 patients were included in this trial by 10 centers in France. At baseline, 16 patients were excluded for major deviation, one patient withdrew consent before any treatment and blood samples were not technically available for 29 participants. All these patients (n = 46) were treated according to current guidelines and were not included for analysis since no data were collected. Thus, RILA and complete RT were performed for 456 patients (90. 8%) before entering follow-up. 434 (86. 5%) patients were followed for at least 36 months according to the protocol. The 22 other patients interrupted the planned follow-up before 36 months (Fig. 1 ).
It was then confirmed by others in prostate  (Foro et al. , 2014) , head and neck  (Bordon et al. , 2010) , and cervix  (Bordon et al. , 2011). PHRC trial 2 (NCT00893035) dedicated to prostate is now closed to recruitment and will be presented with longer follow-up. The mechanism underlying the predictive property of RILA seems to be ubiquitous whatever the irradiated site. The clinical utility of RILA is high as mentioned in the STROGAR guidelines  (Kerns et al. , 2014). For example, patients identified as low risk of late effects might be offered a higher dose with modern techniques or radiotherapy in combination with systemic therapies with the aim of  improving local control. In some cases radiotherapy may be avoided completely for individuals with a high risk of toxicity, provided that an effective alternative exists.
Acknowledgments The authors thank  Ms. Carole Jouet  for data monitoring and  Mr. Michael Coelho  for his excellent technical assistance (lymphocyte assay). The  French National Cancer Institute (INCa)  through the  "Programme Hospitalier de Recherche Clinique  ( PHRC 2005 )" funded this trial. It was also approved and labeled by the  French Society of Radiation Oncology (SFRO). The funding agency has no role in the actual experimental design, analysis, or writing of this manuscript.
5 mg/g animal weight) was realized 1 h before killing. Livers were fixed, and cells in S or M phases were then detected by using anti-BrdU (ab8152, Abcam, Cambridge, UK) or anti-phosphohistone H3 (no. 9701, Cell Signaling Technology), respectively. A co-staining for nucleus was performed with Hoechst. Cell counting was made with the Simple PCI software (Hamamatsu Photonics, Massy, France) on × 20 pictures with at least 500 cells. Caspase 3 activity assay. Fifty milligrams of frozen remnants livers were lysed in caspase 3 activity buffer (20 mM PIPES, 100 mM NaCl, 10 mM DTT, 1 mM EDTA, 0. 1% CHAPS, 10% sucrose, pH 7. 2). One hundred micrograms of proteins were incubated with 100 μM DEVD-AMC at 37 °C for 1 h. The liberation of AMC was monitored using excitation/emission wavelength of 380/440 nm (Gemini, Molecular Devices, Saint Grégoire, France).
Acknowledgements. The authors thank the  Dr. C Lucas-Clerc  from the  Laboratoire de Biochimie Générale, CHU Rennes , the  Animal core facility ARCHE  ( SF Biosit, Université de Rennes 1 ), and the  ImPACcell platform  ( SFR Biosit, Biogenouest, Université de Rennes 1 ). Programme grant support from  Cancer Research UK  ( Professor Roland Wolf ,  C4639/A12330 ) is gratefully acknowledged. This work was supported by the  Institut National de la Santé et de la Recherche Médicale , the  Centre National de la Recherche Scientifique , the  FEDER (Fonds Européens de Développement Régional)  and the  'Contrat de plan Etat région Bretagne ' (axe biothérapie). Ismail Ben Mosbah  was funded by the  'Contrat de plan Etat région Bretagne ' (axe biothérapie) and the  Fondation pour la Recherche Médicale.
, 2012) , resulting in 373,363 contigs (cumulated size: 580 Mb, N50: 3,783 pb, max size: 490Kb, mean size: 1,402bp). This assembly was analyzed at the taxonomic level using the MG-RAST pipeline  (Meyer et al. , 2008). As expected from a gut metagenome, the major clades in the sample were Clostridia (65%) and Bacteroidetes (15%) (Figure  1B ;  Langille et al. , 2014). Interestingly, a similar analysis performed on the DNA sequences using the Kraken program  (Wood and Salzberg, 2014)  confirmed these results but also showed that the major part (ca. 80%) of the DNA sequences could not be attributed to a sequenced organism (data not shown). The contigs were then split into 1-kb fragments. This step had two objectives: first, to alleviate the impact of potential misassemblies arising during the assembly step; second, to normalize the contact signal with respect to the influence of contig size on their representation.
, 2015; Imakaev et al. , 2012). For each enzyme, the normalized percentage of contacts exploited to generate one community was computed (Supplementary Figure  1. 1C). This experiment illustrates the interest of combining two different restriction enzymes to perform a meta3C experiment. By design, the Louvain algorithm does not attribute a node to several communities. Interestingly, when the segmentation was performed twice on the same network some nodes were attributed to distinct partitions, suggesting these communities shared the sequences represented by these nodes. In order to estimate the likelihood that a contig equally connected to numerous subnetwork will be attributed to its appropriate community/ies, Louvain clustering was run five times independently on the same dataset, exploiting the inherent non-deterministic nature of this algorithm (Figure  1E ).
Binning of contigs using 3C contact data An approach similar to the one described in  Marbouty et al. (2014) , based on the Louvain method  (Blondel et al. , 2008) , was used to group the different contigs into communities reflecting the different genomes present in the sequenced mixtures. Before applying the algorithm, contigs were divided into 1-kb chunks corresponding to several nodes in the graph. In order to improve the reliability and stability of the clustering, five iterations of the Louvain algorithm were independently run on the dataset, using its non-deterministic heuristics to determine how often contigs clustered with each other. A set of six such clusters comprising large overlapping communities of contigs was selected for further reassembly by GRAAL.
Acknowledgements We thank  Julien Mozziconacci  for helpful suggestions,  Jean-Francois Flot  for performing the original IDBA-UD assembly and Kraken analysis as well as for fruitful discussions, and  Thierry Pedron  for kindly providing us with the mouse feces. This research was supported by funding to R. K. from the  European Research Council  under the  7th Framework Program  ( FP7/2007-2013 )/ ERC  grant agreement  260822.
Statistical analyses Statistical analyses were performed using XLSTATS software (Addinsoft, Paris, France). Descriptive measures were used to present patients' characteristics and routine tests data: number, percentage, mean (+/-standard deviation, SD). Data between HIV positive and HIV negative patients were compared using a Mann and Whitney test. No a priori power analysis was conducted because we did not know the exact effect size that we would see. A p value of < 0. 05 was required to reject the null hypothesis.
5 KCl, 2 CaCl 2 , 1 MgCl 2 , 1. 25 NaH 2 PO 4 , 26 NaHCO 3 , 25 D-glucose; bubbled with 95% O 2 /5% CO 2 (pH 7. 4). The recording chamber was perfused at a rate of 2-3 ml/min with the same solution supplemented with 10 mM tricine (a Zn 2+ ion buffer,  Paoletti et al. , 1997). Experiments were performed at 32 • C (Single Channel Heater Controller, Warner Instruments, Holliston, MA). Patch pipettes had resistances of 2-4 MΩ and 4-6 MΩ for PCs and MLIs respectively. Cells were voltage-clamped at -70 mV in the whole-cell configuration. Series resistance was held between 4 and 10 MΩ, compensated with settings of 70% for PCs and between 10 and 20 MΩ, compensated with settings of 30-70%, for MLIs. pCLAMP8 software (Molecular Dynamics) was used for data acquisition and analysis. Recordings were filtered at 1 kHz and digitized at 50 kHz.
Pre-embedding immuno electron microscopy in cerebellar tissue from a 24-day-old Wistar rat was performed as described in  Bidoret et al. (2009). Micrographs were analyzed using ImageJ software. MLIs were recognized by their soma and classical nuclear invaginations. PF synapses onto MLI somata were identified by their postsynaptic densities. The quantification of the peroxidase labelling was done on ∼17500 µm 2 for each section, in lobules 5 to 7 of the cerebellar cortex.
ACKNOWLEDGMENTS This work has received support under the program « Investissements d'Avenir » launched by the  French Government  and implemented by the  ANR , with the references:  ANR-10-LABX-54   MEMO LIFE  and  ANR-11-IDEX-0001-02   PSL * Research University. This work was also funded by  PEPS "ICSARP NMDA ", and  Agence Nationale de la Recherche  ( ANR-08-SYSC-005 ,  ANR-08-BLAN-0023 ). GB was funded by  Région Ile de France. We thank  B Barbour  and  M Diana  for comments on the manuscript.
Analysis of Thymocyte Subpopulations Sixteen mice were infected as described above and their thymuses were harvested between 9 and 12 dpi, 4 thymuses plus 1 from control mouse per day (total of 16 acutely Chagas infected mice and 4 controls). The organs were individually squeezed in PBS containing fetal calf serum 10% (Gibco). For analysis of thymocyte subsets, cells were resuspended in mouse serum during 15 min and incubated with specific monoclonal antibodies for 30 min at 4°C in the dark (anti-CD4/APC, anti-CD8/FITC, from BD Pharmingen), followed by washing and analysis on flow cytometer FACS Canto II (BD Biosciences) and using the FACS Diva v6. 1. 3 software. In order to determine specific fluorescence intensity, the background staining values obtained with fluorochrome-matched IgG isotype controls were subtracted.
Quantitative PCR Analysis The fluorescence accumulation data of real-time RT-PCR reactions of each sample were used to fit four parameters sigmoid curves to represent each amplification curve using the library qPCR  (27)  for the R statistical package version 3. 1. 2 (28). The cycle of quantification was determined for each amplification, by the maximum of the second derivative of the fitted sigmoid curve. The efficiency of each amplification reaction was calculated as the ratio between the fluorescence of the cycle of quantification and the fluorescence of the cycle immediately preceding that. The estimated efficiency of each miRNA or gene was obtained by the mean of the efficiencies calculated for each amplification reaction of that precise miRNA or gene. microRNA normalization among the different amplified samples was achieved by the calculation of normalization factors given by the geometric mean of the expression value of all expressed miRNAs in a given sample  (26).
Bioinformatics-Based Enrichment Analysis of miRNA Targets To predict miRNA targets, we identified putative target genes based on predictions from five online softwares: miRanda 1  , Microcosm Target 2  , miRNAMap 3  , miRTarBase  4  , and Target Scan  5. Any gene was considered a putative target if it was predicted in at least three out of the five predicting software. We then performed a gene set enrichment analysis (GSEA) with putative target genes. A gene set was defined as all putative target genes that share the same ontology based on the gene ontology (GO) database  (31). The over representation was assessed with a statistical score based on a hypergeometric test with p-values ≤0. 001. The Rgraphviz package  6  was used to illustrate the relationship between putative targets, miRNAs and biological processes, and in calculations of the k-core structures of the input networks using the degree as centrality measure.
All simulations were performed by means of the software packages XPPAUTO (http:// www. math. pitt. edu/~bard/xpp/xpp. html) and MATLAB. Stochastic simulations. At birth, each cell is assigned a value for k SMPF and V SRUM1 from a uniform distribution centered on the deterministic values given in S3 Table. More precisely, k SMPF = (1 + σ SMPF Ãr)Ã0. 05, where σ SMPF is a constant (0 < σ SMPF < 1), r is a uniform random deviate on [-1, 1], and k SMPF = 0. 05 is the deterministic value. V SRUM1 is computed from a similar equation, with σ SRUM1 determining the cell-to-cell variations in the rate of synthesis of Rum1. To estimate σ SMPF and σ SRUM1 , we performed a series of stochastic simulations for different values of these parameters, in each case calculating the distribution of cell size at division for MCN and MCN-AF cells.
CG thanks the  Foundation Philippe Wiener -Maurice Anspach  for financial support. JJT is supported by a grant from the  NIH  (Grant  5R01-GM078989-07 ). DC is supported by funding from the  ERC  under the European Union's  Seventh Framework Programme  ( FP7/2007-2013) / ERC Grant agreement n°310849. BN receives support from the  EC 7th Framework Program  ( MitoSys -241548 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subsequently, the microelectrodes were connected to the pulse delivery equipment and the pulse generation was initiated (8 biphasic pulses, duration 100 µs positive + 100 µs delay + 100 µs negative, frequency 1 Hz). When the trigger signal from the pulse generator was detected by the PXI-2530 system, the connections were switched to the measuring system after a fixed delay of 15 ms. Subsequently, 860 multisine bursts were continuously generated and acquired. The connections were again immediately switched to the pulse generator and the system waited for the next pulse (125 ms). The sequence was repeated until completing the 8 pulses. The sequence of electroporation and measurement signals is detailed in Schematic 1b. The complete system was controlled by a custom software in Labview (National Instruments).
Data pre-processing The bioimpedance was estimated by measuring and processing an integer number of periods of the sample current and voltage response. The impedance was calculated on the basis of the division of the output-input Fast Fourier Transform (FFT) coefficients at the excited frequencies  [38]. Once the impedance was calculated, noise reduction was performed with a moving average filter (length n=10) independently for each 860 ms continuous measurement segment. Compensation for the effects of the system frequency response produced by the microelectrodes, cables, amplifiers, etc. , was achieved by means of a three-reference calibration method  [39]. The references were obtained by measuring, with the same setup, saline solutions with different conductivities (approx 0. 1 ± 70 % S/m).
Experimental procedure To conduct the experiments, the cells were removed from the incubator and washed once with LCE buffer. Subsequently, 200 µl LCE + Yo-Pro (1 µM) were added. The cells were then introduced into a controlled temperature chamber at 37 • C and left to stabilize for 10 minutes before pulse application. The complete experiment was performed in this controlled temperature environment. After this period, the microelectrode assembly was manually positioned above the cell monolayer by means of a custom-built applicator. Prior to their positioning above the cell monolayers, electrodes were wetted in LCE buffer. Immediately after, the Labview software which controls the whole system initiated the electroporation-measurement sequence described above. Once the sequence was finished, the microelectrodes were carefully removed and the cells were left for and additional 15 minutes for resealing.
In Fig. 2a  (dots) the data and the corresponding adjusted Cole model (blue line) of the initial (pre-electroporation) monolayer impedance of a single experiment are plotted in a Wessel diagram. The measurements clearly describe a single dispersion arc compatible with the Cole model. Subsequently, all data sets (100 + 8x860) were adjusted to the model with a MATLAB routine. Fig. 2b  shows the evolution of the Cole arcs during the complete electroporation treatment (E=1200 V/cm,8 pulses, 1 Hz) of the same sample. The temporal evolution of Cole model parameters R 0 and R ∞ is shown in Figs. 2c  and d. The observation of R 0 evolution reveals two different dynamic processes. First, a fast recovery of the impedance values in accordance with the resealing of plasma membrane immediately after each pulse application is detected (short-term evolution).
Short-term analysis We first focus on the transient impedance recovery observed in R 0. In order to make an independent analysis of this process, it is necessary to separate it from the superimposed long-term decay observed. Fig. 3a  shows an illustrative example of the obtained long-term evolution (dashed lines) for each electric field condition. This component is then subtracted from the original data to obtain the corrected short-term information. The corrected mean value (± SD) of the short-term dynamics for at least three repetitions of each electric field is shown in Fig. 3b. The analysis of the fast impedance recovery after each pulse can now be studied independently. A double exponential behaviour according to Equation 4 is proposed to follow this short-term impedance evolution. In order to determine a quantitative measure of the time constants for this dynamic evolution, the 8 fragments of measurements corresponding to each inter-pulse window are individually processed in MATLAB to obtain the values of the time constants τ 1 and τ 2.
ACCEPTED MANUSCRIPT The analysis of the electrical equivalent is only shown for an illustrative example, which is valid for demonstrating the effectiveness of the model and its interpretation. The data corresponds to a single experiment applying 1200 V/cm; the same analysis was performed for the other conditions and shows a similar behaviour. First, the values for the initial pre-electroporation state are found manually in order to set the initial conditions to the fitting algorithm. Subsequently, circuit parameters are obtained automatically for each spectrum. During the course of the fitting procedure, it was noticed that there was more than one possible set of parameters solving the system. For this reason, some restrictions were imposed on the algorithm in accordance with the expected evolution of the parameters.
Sections were then incubated with anti-TH antibody (1/5000, rabbit, AB152 Milipore USA) diluted in DAKO REAL antibody diluents overnight at room temperature. The next day, the presence of the epitope was revealed using the DAKO LSAB and HRP system (DAKO Real, DAKO France). The reaction allowed localizing the expression of TH by brown labeling on the slides. In order to reduce the differences in background labeling between all the slides, all the slides from the experiments were processed at the same time for TH immunohistochemistry under the same laboratory conditions. TH-positive neurons were counted using ImageJ software on 12 slices from the anterior to posterior axis of the brain. The numbers of positive cells in both VTA and SN were estimated with the method described by  Paillé et al.
In order to reduce the differences in background labeling between all the slides, all the slides from the experiments were processed at the same time for D3R immunohistochemistry under the same laboratory conditions. Observation of the fluorescent labeling was done using a Zeiss microscope and AxioVision software. The number of positive cells was counted in 100 µm² square windows, positioned at the same place using a brain atlas. In the Acb, one window was used for the core region and one window for the shell region. The numbers of positive cells was noted as the mean number of cells per 100 µm².
Methods and Findings We conducted a systematic review by searching three bibliographic databases. We included human studies addressing the relationship between whole grain consumption and T2D occurrence, and providing quantitative information on daily intake of whole grains. A dose-response meta-regression analysis between whole grain intake and T2D occurrence was performed, using a hierarchical mixed least square linear regression model. Eight observational studies were included (all but one prospective), with a total of 15,573 cases of T2D among 316,051 participants. Quantitative meta-regression demonstrated a significant linear inverse relationship between whole grain intake and T2D occurrence (P<0. 0001), with an overall absolute reduction of 0. 3% in the T2D rate for each additional 10 g of whole grain ingredient consumed daily.