dataesr/scientific-paragraphs-categorization huggingface dataset:
The images were captured and analyzed with a Zeiss Observer Z1 microscope. Quantifications were performed using Histolab software (Microvision, France). For the immunofluorescence assay, tumor slices were incubated with CD31, CD10, or von Willebrand factor (FvW) primary antibodies, followed by incubation with the secondary antibodies. Nuclei were stained with DAPI. Image analysis was performed using Zeiss Observer Z1 fluorescent microscope and AxioVision software. For the human samples, CD31/ CD10 double immunofluorescence analyses were performed on 5-µm formalin-fixed paraffin-embedded tissue sections. Primary antibodies CD10 (clone: 56C6, 1:10, Novocastra, Leica, France) and CD31 (clone: JC70A, 1:4, Dako, France) were bound with Alexa 555 (APEX Alexa fluor ® 555 Antibody labeling kit, Invitrogen, France) and Alexa 488 (APEX Alexa fluor ® 488 Antibody labeling kit, Invitrogen, France) respectively.
Double immunofluorescent staining was performed on a Discovery XT (Roche, France) by coincubating tissue sections with the two bounded primary antibodies. Tissue sections were analyzed on a motorized Z-axis BX63 Olympus microscope (Rungis, France). Each fluorescent immunostaining was captured through a UPlan Fl/40 × /0. 75 objective with a digital camera DP71 using Olympus CellSens Dimension software (Olympus, Rungis, France), using specific wavelength for fluorophore excitation. Merged pictures were performed to assess the co-localization of CD10 and CD31.
Results were expressed as n-fold differences in target gene expression relative to the TBP gene (an endogenous RNA control) and relative to a calibrator (1× sample), consisting of the cell line sample from our tested series that contained the smallest amount of target gene mRNA. For microarray experiments, isolated RNA from each tumor was amplified, and biotin-labeled using Illumina TotalPrep RNA Amplification Kit (Illumina, San Diego, CA, USA). 750 ng of biotinylated aRNA was then briefly heat-denatured and loaded onto expression arrays to hybridize overnight. Following hybridization, arrays were labeled with Cy3-streptavidin and imaged using the Illumina ISCAN. Intensity values were transferred to Agilent GeneSpring GX microarray analysis software and data was filtered based on the quality of each call.
Statistical relevance was determined using ANOVA with a Benjamini Hochberg FDR multiple testing correction (p-value < 0. 05). Data were then limited by fold change analysis to statistically relevant data points demonstrating a 1. 75-fold or greater alteration in expression of each gene when averaging the normalized values from each sample within an experimental group. Omics pathway analysis was performed with Metacore integrated software suite (www. portal. genego. com) and functional association networks were created using the String database (www. string-db. org).
Statistics All statistical analyses were performed using GraphPad Prism, Version 5. 00, GraphPad Software. A nonlinear regression curve fit (1-phase exponential decay) was used to analyze dose response experiments. Twotailed unpaired t test was used to calculate the significance of differences between groups (NS, not significant; *P < 0. 05; **P < 0. 01; and ***P < 0. 001). Kaplan-Meier curves were constructed for survival analysis.
Because the current applied is high compared to the physiological current involved in ion exchange, the test can be considered a "stress test" for sweat glands. Two measurements on three different Sudoscan devices were performed under usual testing conditions on each HV and PTD2. Measurements were performed in the same order for all subjects: first measurement on devices 1, 2, and 3 and then second measurement on devices 3, 2, and 1. Electrodes were cleaned after each test and an interval of at least 5 min was observed between two successive measurements. A blind analysis of the data was performed by an independent party.
Statistical analyses Comparison of measures recorded at different times on the three different devices was performed according to the ISO 5725-2 standard "Accuracy (trueness and precision) of measurement methods and results -Part 2: Basic method for the determination of repeatability and reproducibility of a standard measurement method"  (25). Results for quantitative variables are shown as means ± SD. The data management and statistical analysis were done using SAS version 9. 4 and R version 3. 2. 1. Bland-Altman analysis was used to assess agreement and bias between two measurements performed on the same device. Intraclass correlation coefficient (ICC) was calculated with the mean values obtained on each device to compare reproducibility between the three devices.
ReSULtS The databases for this Report have been deposited in a public repository (figshare). Access is provided using the following link: http://figshare. com/s/f7792f2093c411e5b7e706ec4bbcf141 -Demographics. xlsx contains the demographic information of the healthy controls and diabetic patients, with each individual denoted as the letter "S" followed by an Arabic numeral; -Reproducibility_healthy controls. xlsx contains the Sudoscan ESCs recorded for each subject for the hands (first sheet) and the feet (second sheet). The repeatability and reproducibility analyses are compiled for the hands ESC on the third sheet and for the feet ESC on the fourth sheet. -Reproducibility_diabetic subjects. xlsx contains the Sudoscan ESCs recorded for each subject for the hands (first sheet) and the feet (second sheet).
NMR spectroscopy Spectra were recorded at 298 K using a Bruker Avance III 700 MHz spectrometer equipped with a triple resonance-gradient standard probe. Topspin version 2. 1 (Bruker BioSpin) was used for data collection. Spectra processing used NMRPipe  (Delaglio et al. 1995)  followed by analysis with Sparky 3 (T. D. Goddard and D. G. Kneller, University of California) or NMRviewJ 8. 0 (One Moon Scientific). For backbone resonance assignment of 300 µM 13 C, 15 N MEC-8 RRM1 the following spectra were used: 2D 1 H-15 N HSQC, 3D HNCO, 3D HNCA, 3D HNHA, 3D (H)CCONH TOCSY, and 3D H(C)CONH TOCSY. All spectra were collected in buffer containing 90% H 2 O/10% D 2 O. Amide 15 N T1 and T2 relaxation data were acquired at 700 MHz and 298 K as previously described  (Farrow et al. 1994). Steady-state heteronuclear { 1 H} 15 N-NOE spectra were recorded with and without 3 sec of 1 H saturation.
Crystal cryo-protection involved soaking for 5 min in a solution composed of 6. 7% (v/v) isopropanol, 6. 7% (v/v) PEG4000, and 25% (v/v) glycerol. Diffraction data were collected at the European Synchrotron Radiation Facility beam line ID23-2 and processed using the program XDS  (Kabsch 2010). The unbound structure was determined by molecular replacement with Phaser  (McCoy et al. 2007) , based on the crystal structure of the second RRM domain of yeast poly(U)-binding protein PDB 3MD1 chain A. Molecular replacement for the DNA-bound complex used the unbound MEC-8 RRM1 dimer. Phenix was used for refinement  (Adams et al. 2010). A summary of data collection and structure refinement statistics is provided in Supplemental Table  S1. Structure images were prepared by using the program Chimera  (Pettersen et al.
ACKNOWLEDGMENTS We thank  Gavin Collie  for final preparation of crystals and synchrotron data collection. Additional assistance and advice were provided by  Lionel Beaurepaire ,  Brice Kauffmann ,  Axel Innis , and  Sébastien Fribourg. Brune Vialet  provided synthesis of the RNA oligonucleotides. Access to NMR spectrometers, equipment, and technical assistance were possible thanks to  Axelle Grélard ,  Estelle Morvan , and the structural biology platform at the  Institut Européen de Chimie et Biologie  ( UMS 3033 ). We thank the  European Synchrotron Radiation Facility  for access to synchrotron radiation facilities (beam line  ID23-2 ). Financial support from the  Centre Nationale de la Recherche Scientifique  ( IR-RMN-THC Fr3050 ) is gratefully acknowledged. H. S. was supported by a PhD fellowship from the  Institut National de la Santé et de la Recherche (INSERM)  and the  Aquitaine regional government.
Acknowledgments Supported by the  Fondation pour la Recherche Medicale, Agence National pour la Recherche and Association Francaise contre les Myopathies. Open Access This chapter is distributed under the terms of the Creative Commons Attribution-Noncommercial 2. 5 License (http://creativecommons. org/licenses/by-nc/2. 5/)which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. The images or other third party material in this chapter are included in the work's Creative Commons license, unless indicated otherwise in the credit line; if such material is not included in the work's Creative Commons license and the respective action is not permitted by statutory regulation, users will need to obtain permission from the license holder to duplicate, adapt or reproduce the material.
Data, imaging, and EUS-FNA at inclusion The clinical data recorded were age, gender, medical history, circumstances of diagnosis, and symptoms related to IPMN. All patients underwent helical triple-phase CT examinations and MRCP was performed in 81 % of patients  [8, 11]. EUS-FNA procedures were performed, as previously described  [8, 11, 26]  (Olympus GF-UC140 T echo-endoscope -Hamburg, Germany). Data recorded at imaging were maximal diameter of the MPD and branchduct cyst, the tissular component surrounding the MPD, mural modules and/or tissular thickening of the MPD and/or BD cyst wall (mainly at EUS), localization of BD lesions, and maximal diameter of the side-branch IPMN. In each patient with predictor signs of malignancy, a fine-needle aspiration of cystic fluid was obtained using a Wilson Cook USN1 22G needle biopsy (Limerick, Ireland).
! In this prospective study, we investigated a subgroup of IPMN patients who had clinical predictors of malignancy assessed at diagnosis. We demonstrated that when the KRAS-mutation analysis was added to the cytopathology data from EUS-FNA materials, this improved the ability to diagnose malignancy. This is of importance as it will improve our ability to identify patients with high-grade dysplasia or invasive malignant IPMN and who might benefit from surgical resection. We also observed that testing for the GNAS mutation did not improve the performance of cytopathology alone or the combination of cytopathology plus the KRAS assay to diagnose this indication. As previously observed in solid tumors, despite the paucity of material collected for molecular analysis from IPMN cystic fluid, which rarely excesses 500 µl, DNA extraction can be performed in 100 % of cases  [27].
Numerical simulations of regeneration in the presence of bone defect In order to describe the physical situation in which a hole is produced inside bone tissue, the continuum mixture model proposed in Section 3 can be used. We consider the geometry reproduced in Figure  3 : our specimen is composed of a rectangular-shaped bone sample 1 cm × 1 cm, with a circular-shaped hole in the center with a diameter of 2 mm. Since no bio-material is present inside the cavity, we will assume that no resorption of considered "fictive material" occurs by setting r m = 0 (see Table  1 ). Furthermore, it was assumed that the thickness d of the specimen was equal to 1 mm. These hypotheses allow us to adopt the theoretical model introduced in the previous section to describe bone growth inside a hole. The model was implemented within the COMSOL Multiphysics(R) software (see Figure.
2. 1. Participants. The study sample was recruited in six languages (The Netherlands, UK/USA, Finland, France, Germany, and Italy). Data from this patient sample was also published in von Steinbüchel et al. [16, 17]. Around 45% of the patients were in outpatient treatment during participation in our study, and the other did not receive any treatment during the assessment. Inclusion criteria entailed the following: ICD-10 diagnosis of TBI, minimum age at injury of 15 years, 17-68 years of age at interview, outpatient treatment (currently not admitted to a ward), and ability to provide informed consent. By the inclusion criterion "outpatient treatment" the exclusion of patient being currently admitted to a ward was intended. Exclusion criteria were as follows: a Glasgow Outcome Score Extended (GOSE)  [36]  below 3, serious current or preinjury psychiatric issues, current severe addiction, diagnosis of a terminal illness, inability to cooperate in the study, and incapability to understand and answer the questions.
Data Analysis. Concerning the generic and diseasespecific HRQoL instruments (SF-36 and QOLIBRI, resp. ) classical psychometric criteria were investigated (mean, standard deviations (SD), skewness of item distribution, floor and ceiling effects per scale, kurtosis, and Cronbach's alpha, as well as convergent and discriminant validity). Probabilistic test theoretical analyses have already been applied for the QOLIBRI  [16]. Frequencies, means, SD, and percentages are given for the covariates/correlates of HRQoL. Kolmogorov-Smirnov  [42]  and Shapiro-Wilk test  [43]  were used to test if the data were normally distributed. Ceiling and floor effects were defined as answers which fell into the highest or lowest 10% of possible answers per subscale. These effects should be minimal for an instrument to be able to discriminate well.
To be able to investigate whether disease-specific and generic HRQoL share similar correlates, the QOLIBRI Total score and SF-36 MCS and PCS representing the outcomes (predicted values) and a number of sociodemographic, psychosocial, and health-related variables, known from the literature as predictors and correlates, were submitted to a stepwise linear regression analysis (SPSS 22. 0). The variables included in the first step were as follows: Years since Injury, Age, Relationship Status, Education, Change of Job, Employment, Living Arrangement, the Degree of Help Needed, Independence, Social Activities, Internet Activities and other Hobbies, Comorbid Health Conditions, Sensory and Psychosomatic and Motor-Skeletal Complaints, GOSE score, and HADS Depression and Anxiety scores. As many of the variables were skewed, we ranked data before subjecting them to regression analyses  [44].
However, in HRQoL research SI has been defined using logarithm base 2 in the formula  [34]. In order to assure continuity we decided to define the Shannon index by logarithm base 2. Therefore, we also determined that each score defined a category. After summing up the answers of each person to an individual person score, these scores were used as categories. No grouping was applied. max is therefore estimated; it is defined as the maximum value of   (  max = log 2 (  )) and indicates the maximum available information. The second index in the context of the Shannon index is   and is derived from. presents a measure for the spread of the frequencies or categories  [34]. The advantage of   , unlike   , is its independence from the number of categories available in the dataset. Statistically,   quantifies how equally the numbers of categories are distributed.
The type of language used in the messages was also assessed (Table  2 ). No coding process (manual or software aided) was used since the media content analysis method does not require it but several descriptors were 'counted' , such as the number of posts that used a 'cautious tone' , or complained about poor medical practices. The blog data was categorized according to pre-established recurrent themes. Frequencies were calculated using Excel Office 2011. The following quotes extracted from the blog testimonies were translated from French to English by the third author and verified by the first author. The blog entries (n = 196) selected for analysis were retrieved on July 17th, 2013, and included posts made over several years, between January 2008 and June 2013. This time frame matched a period during which media attention was high and public discussion evident in response to the Haute Autorité de Santé's decision on PC screening.
Study design and patients The observational, multicenter study sponsored by Clovis Oncology enrolled patients between April 2011 and June 2013 and was designed to prospectively collect matched blood and tumor tissue from newly diagnosed or relapsed patients with advanced (stage IIIB, IV) NSCLC. The observational study protocol allowed enrollment of patients without a requirement for documented evidence of an EGFR mutation. Data from local testing is incomplete; only central testing results are presented here. Eligible patients were undergoing, or had recently undergone, a clinically indicated biopsy or rebiopsy and signed an Ethics Committee/Institutional Review Board (EC/IRB)-approved consent prior to donating a blood sample and matched FFPE tumor tissue. Patients in the observational study did not receive rociletinib.
001; Fig. 2B  and C ). We were able to confirm these initial observations in 72 patients, 34 of which overlapped the initial BEAMing dataset, using the cobas EGFR plasma test (P < 0. 001; Supplementary Table  S7 ). We performed a logistic regression analysis to look for other clinical characteristics that might predict the ability to identify EGFR mutations in plasma including M stage, age, gender, race, performance status, smoking status, tumor burden, or lines of previous therapy. No variables other than M stage were associated with the ability to identify EGFR mutations in plasma (data not shown).
A strength of our study is that >90% of all cases evaluated had matched tumor tissue and plasma prospectively collected within 60 days of one another. With tissue as the reference method, the positive percent agreement (PPA) observed for activating mutations between plasma and tumor was 82% for BEAMing (49/60) and 73% for the cobas test (55/75). These results are similar to data for the cobas test from an analysis of 238 Asian lung cancer patients  (22). They also compare favorably with two large studies that used allele-specific PCR (43%; 22/51; ref. 28)  and (66%; 69/105; ref. 10) , one that used protein-nucleic acid (PNA)-mediated PCR (59%; 97/164; ref. 1) , and one that used a denaturing high-performance liquid chromatography (DHPLC) method (82%; 63/77; ref. 29 ). Higher sensitivities have been observed for blood with respect to tumor, but these have been in small studies of fewer than 20 patients  (30, 31).
Patients We conducted a retrospective multicenter study of patients with TA in whom aortic surgery was performed and aortic tissue specimen was available for analysis. All patients fulfilled the American College of Rheumatology and the Sharma-modified Ishikawa criteria for TA  (10, 11). Demographic, medical history, laboratory, imaging findings, including 18 F-fluoro-deoxyglucose positron emission tomography (FDG-PET), computed tomography angiography (CTA), and/or magnetic resonance imaging (MRI), treatment, and follow-up data were extracted from medical records. The patients' clinical, laboratory, and imaging data, as well as treatments were analyzed at disease onset and at time of surgery. Routine laboratory tests, including C-reactive protein levels, were collected, and disease activity was defined according to the NIH criteria  (12).
Expression analysis were performed using the Limma package to identify genes that met statistical significance (P < 0. 05 after adjustment according to the method of Benjamini and Hochberg and fold-change criteria (at least a 1. 5-fold change) for differential expression using the following contrasts: macrophages infected with live parasites at a given time point versus non infected macrophages incubated with vehicle (media) for the same time. The same contrast was used for heat-killed Leishmania-infected macrophages. Macrophage genes modulated during the kinetics were first detected. In accordance with MIAME (Minimum Information About a Microarray Experiment) regulations, all data were deposited into GEO (Gene Expression Omnibus) database at www. ncbi. nlm. nih. gov/geo/ under the accession number GSE31995.
Ingenuity global functional analysis Ingenuity Pathways Analysis (IPA; Ingenuity, CA; Systems 2008) tool was used to identify relevant lipid canonical pathways in macrophages that were altered by Leishmania parasite infection, based on a Fischer's exact test to calculate a p-value for each biological function founded (at least P < 0. 01). A list of the statistically significant differential genes expression in L. majorinfected BALB/c macrophage related to lipids for each measured time point was generated and mapped to their functional networks in the IPA database. This analysis shows the number of Leishmania modulated genes belonging to a given pathways which are ranked by the obtained score. The relationships between the generated networks and known pathways were then investigated using the canonical pathway analysis function.
LD evaluation in live cells For live imaging, macrophages were seeded in 96 well plates (Optical Bottom Plate, Black Polystyrene, Cell Culture Treated and Sterile; Thermo scientific) and infected with transgenic Ds-Red or WT parasites for time-courses ranging from 15 min to 24 h. Extracellular parasites were then washed out and cells were stained with Bodipy for LD tracking. 3D confocal time-lapse imaging was performed at 37°C using a PerkinElmer UltraVIEW VoX spinning disk attached to an Eclipse Ti inverted microscope (Nikon) with a 40X/1. 3 N. A. dry objective. Images were collected sequentially in two channels (488 and 561nm laser) every 5 to 30 min for 1, 3, 6, 12, 18 and 20 h post infection. Acquisition was performed and analyzed using Volocity analysis software. Quantification of LD accumulation in contact with L.
Statistical analysis Results are representative of at least 3-6 independent experiments. The data are presented as the mean plus SEM (standard error of the mean) and were analyzed using the Graph-Pad Prism 5. 03 software (GraphPad Software, San Diego California USA, "www. graphpad. com"). The experiments were analyzed using One-way analysis of variance (ANOVA) with Dunnett's or Bonferroni's test for the comparaison of three or more groups of data and Unpaired Student T-test for the comparaison of two groups of data. The differences were considered statistically significant when p <0. 05 ( Ã ), p <0. 01( ÃÃ ) and p <0. 001 ( ÃÃÃ ).
Furthermore, the set of genes related to lipid pathways was also analysed through Ingenuity Pathways Analysis Software (Ingenuity Systems, Redwood City, CA; http://www. ingenuity. com) (IPA). Even if these genes are expressed with different dynamics throughout the kinetic, the final number of modulated genes remains the same for each time point which explains the absence of variation of each lipid pathway across the time course of infection. Nevertheless, this analysis reveals according to their score that glycerolipid, eicosanoid and fatty acid metabolisms are among the top ten lipid pathways modulated by the parasite (Fig 2  and S1 Table). In addition, a number of genes coding for lipid droplets related proteins involved in the de novo TAG biosynthesis and hydrolysis and the accumulation of cholesterol are found significantly activated in L.
Localization of LD in Leishmania major infected macrophages To study the dynamics of the LD-Leishmania association in living cells, a time-lapse sequence of BMMs infected with DsRed transgenic parasites was investigated using confocal microscopy. The accumulation of LDs appears as early as 15 min post infection and massive LD accumulation is observed throughout the measured time-course. Our results also show, that while most of the LDs are found in parasite free cytoplasm, a subset of LDs co-localizes with the intracellular DsRed parasites. Interestingly, we also notice using live cell imaging, an LD accumulation on some of the extracellular infectious parasites as observed by 3D image reconstruction (Fig  5A ). We thus quantified LD recruitment from cell cytoplasm to intracellular parasites during the live time lapse imaging by measuring LD fluorescence intensity coming to the contact of DsRed-parasites using ImageJ software.