dataesr/scientific-paragraphs-categorization huggingface dataset:
c. tumor due to software limitations and complexity of further calculations during image pre-processing and analysis. Spectral data were acquired in transmission mode. All measurements were recorded using a spectral resolution of 8 cm -1 and averaged to 4 scans per pixel on spectral range 800 to 4000 cm -1. A background spectrum was collected (120 accumulations, 8 cm -1 resolution) apart from the sample to ratio against the single-beam spectrum. Resulting spectra were then automatically converted into absorbance. Further analyses were performed using in-house algorithms written in Matlab (The Mathworks, Natick, MA). A modified Extended Multiplicative Signal Correction (EMSC) method was used to numerically correct the contribution of paraffin in FT-IR spectra  74  as well as to eliminate spectra with low signal-to-noise ratio  75.
As the 1338 cm -1 is a very small absorbance band, second derivative analysis of spectra was also performed to facilitate peak identification and to confirm the distribution at that wave number. For quantitative analyses, similar threshold value and color-map were applied to FT-IR images, which were then imported into ImageJ software as 8-bit gray-scale intensity images, resized and normalized before binarization so as to isolate areas corresponding to collagen deposition from the rest of the tissue. The percentage of stained pixels (collagen) within each tumor sample was measured.
Polarized light microscopy. For studying ECM collagen organization, de-paraffinized slides were stained using Abcam picrosirius red stain kit (ab150681) according to the manufacturer's instructions. Picrosirius staining may be viewed using polarized light resulting in birefringence of the collagen fibers and distinction between type I (thick fibers, red birefringence) and type III (thin fibers, green birefringence) collagen. Slides were imaged in dark-field using a Zeiss Axiovert 200 M microscope equipped with cross-polar optics and a CCD camera. Images from each slide were captured at ×63 magnification in 3 different locations per animal. For each microscopic field, color channels were split in ImageJ software before thresholding so as to quantify the percentage of red and green pixels as well as the corresponding type I/type III ratio.
Mean red and green intensities were also calculated for each image and then averaged. To assess the basketweave structure of collagen, an innovative bioimaging approach combining Fast Fourier Transform (FFT) with Gabor filtering was applied  41. Picrosirius red images were first converted to monochrome grey scale into ImageJ software and then a 3 × 3 median filter was applied to remove photon noise generated during image acquisition. Gabor filtering was performed using ω direction values of 45° + 225°, 90 + 270°, 135 + 315° and 0° + 180° so as to detect and highlight collagen fiber edges. Before FFT processing, windowing was performed on Gabor-filtered images in order to minimize vertical and horizontal discontinuities at the image edges, that may result in artefactual lines in the frequency domain.
37. Red and blue circles respectively stand for low and high LUM mRNA expression in 2 groups designed for further survival analysis. (d) Kaplan-Meier analysis for overall survival rates of 44 melanoma patients grouped by LUM mRNA expression. Logrank test raw p value is indicated. (e) Box-plot shows LUM expression across risk groups from TCGA dataset (SurvExpress tool), including the p value testing for difference using t test. Heat map displays LUM expression in risk groups, with low expression being represented in green grades and high expression in red grades. Calculated β coefficient from the Cox fitting (i. e. linear relationship between gene expression and prognostic index) was -0. 121 for LUM gene. (f) Overall survival Kaplan-Meier plot for high (blue) and low (red) LUM-expressing risk groups is shown, with logrank p value being indicated.
Right panels display corresponding second derivative spectra so as to facilitate peak identification (blue dotted line). (i) Representative binary images separating collagen from the rest of the tumor tissue after FT-IR microimaging of collagen deposition (1338 cm -1 area). (j) Quantification of the number of collagen pixels relative to total tumor pixels (%) implanted in Lum +/+ (WT) vs. Lum -/-mice (mean ± SEM, t test, *p < 0. 05), as performed using ImageJ software.
Acknowledgements This work was supported by grants from  SATT Nord ,  Région Champagne-Ardenne  and  Centre National de la Recherche Scientifique (CNRS). The authors acknowledge Pr. Shukti Chakravarti  ( John Hopkins University School of Medicine, Baltimore, MD ) for kindly providing us with the Lum -/-mouse line. The authors thank  P. Lecuivre ,  A. Pigeon  and  S. Dukic  for animal care, and are grateful to  Pr. G. D. Sockalingum  and  Dr. O. Piot  for discussion and advice.
Whole exome sequencing DNA samples were assembled into Illumina paired-end pre-capture libraries; the oligonucleotide sequences and protocol are available on the Baylor College of Medicine Human Genome Sequencing Center (HGSC) website (http://www. hgsc. bcm. edu/content/protocolssequencing-library-construction). Two, four, or six pre-capture libraries were pooled together, hybridized to the HGSC VCRome 2. 1 design  [33]  (42Mb, NimbleGen), and sequenced in a single lane on the Illumina HiSeq 2000 or the HiSeq 2500 platform. The HGSC Mercury pipeline (https://www. hgsc. bcm. edu/content/mercury) conducted the Illumina sequence analysis while the Consensus Assessment of Sequence and Variation program de-multiplexed the pooled samples. The Burrows-Wheeler Alignment  [34]  algorithm mapped reads to the Genome Reference Consortium Human Build 37 (GRCh37) sequence, producing Binary Alignment/Map (BAM) files.
In addition, SNVs with total coverage<10-fold and indels with total coverage<30-fold were excluded. Individuals were excluded for sex-mismatch, missingness>20%, singleton counts of 0, or values>6 standard deviations from the mean for singleton counts, race-specific mean depths, TiTv ratios, or heterozygote to homozygote ratios. The mean depth of coverage was 109. 6 and 82. 7 for AAs and EAs, respectively. The annotation file included quality-controlled variants observed in at least one available exome sequencing project (e. g. CHARGE, the NHLBI Exome Sequencing Project). Variants were annotated using ANNOVAR  [37]  and dbNSFP v2. 0 according to GRCh37 and RefSeq. This multiple study SNPinfo file was used as a component of the R package seqMeta (http:// cran. rproject. org/web/packages/seqMeta/index.
The  ARIC Study  is carried out as a collaborative study supported by  National Heart, Lung, and Blood Institute contracts  ( HHSN268201100005C ,  HHSN268201100006C ,  HHSN268201100007C ,  HHSN268201100008C ,  HHSN268201100009C ,  HHSN268201100010C ,  HHSN268201100011C , and  HHSN268201100012C ). ARIC Neurocognitive data was collected through the joint support of the  National Heart, Lung, and Blood Institute ;  National Institute of Neurological Disorders and Stroke ;  National Institute on Aging ; and the  National Institute on Deafness and Other Communication Disorders  ( U01 HL096812 ,  HL096814 ,  HL096899 ,  HL096902 ,  HL096917 ), with previous brain MRI examinations funded by  R01 HL70825  from the  National Heart, Lung, and Blood Institute. This work was supported by the  Framingham Heart Study (NHLBI/NIH  contract  HHSN268201500001I  to the  Boston University School of Medicine ) and by grants from the  National Institute on Aging  ( R01 AG008122 ,  R01 AG054076 ,  R01 AG049607 ,  R01 AG033193 ,  U01 AG049505 ,  U01 AG052409 ) and the  National Institute of Neurological Disorders and Stroke  ( NS017950  and  UH2 NS100605 ).
Study design We performed ancillary analysis of prospectively acquired data in the frame of the ASAINT study (NCT02599974). ASAINT aimed at evaluating the diagnostic performance and the prognostic value of 18 FDG-PET/CT in patients with stage II or III breast cancer undergoing neoadjuvant chemotherapy. The main objective of the present study was to compare the value of some clinicopathological parameters and PET-derived image indices in predicting event-free survival (EFS) in the subgroup of ER+/HER2-breast carcinoma. The secondary objective was to examine the association between baseline PET image parameters and tumor characteristics. The study was approved by the institutional review board with waivers of informed written consent for this ad hoc analysis of image-derived data.
FDG-PET/CT imaging Patients fasted for 6 hours and blood glucose level had to be less than 7 mmol/L. Imaging started 60 minutes after injection of 18 FDG (5 MBq/kg); a 2 minutes per bed acquisition was performed from mid-thigh level to the base of the skull with the arms raised. The same PET/CT scanner was used for all the patients: the Gemini XL (Philips Medical Systems, Amsterdam, The Netherlands). CT data were acquired first (120 kV; 100 mAs; 0. 813 pitch factor; no contrast enhancement). CT images were reconstructed with a pixel size of 1. 17 mm. Reconstruction section thickness was 3 mm and the reconstruction interval was 2 mm. PET images were reconstructed with a isotropic voxel size of 4 mm. Accurate registration of CT reconstructed and PET reconstructed images was obtained by annual system alignment calibration of the bed, CT gantry, and PET gantry.
Funding LO acknowledges funding from the  French Government 's " Investissement d'Avenir" program, Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases " (grant no. ANR--10--LABX--62--IBEID ) and from  Région Île--de--France  ( Domaine d'Intérêt Majeur Maladies Infectieuses ). RME acknowledges funding from the  National Institute for Health Research  through the  Health Protection Research Unit in Immunisation at the London School.
Significance analysis of microarrays (SAM) revealed that 190 transcripts were downregulated in spindle cell compared to non-spindle cell MBCs (Supplementary Table  9 ). Functional annotation and pathway analysis of these transcripts using the Ingenuity Pathway Analysis (IPA) software revealed that MBCs with spindle cells displayed lower expression of tight-junctionrelated genes, including CLDN3, CLDN8, CGN, MYH11, and MYH14 (p-value < 0. 05, Supplementary Fig. 5 ) than other forms of MBCs. Additionally, spindle cell MBCs differentially expressed EMT-related genes compared to squamous and chondroid MBCs, including reduced CDH1 and EPCAM expression (Supplementary Table  9 ). The down-regulation of EMTrelated genes in spindle cell MBCs, including claudins, is consistent with their claudin-low intrinsic subtype.
MBCs are not driven by a recurrent fusion gene or an expressed pathognomonic mutation in cancer genes To determine whether MBCs are driven by a highly recurrent fusion gene, we subjected the 17 MBCs to paired-end RNAsequencing. Analysis using defuse  26  and ChimeraScan 27 identified 43 fusion transcripts (Supplementary Table  19 ). Akin to the gainof-function oncogenic fusion genes identified in other special histologic types of breast cancer,  12, 13  we prioritized fusion transcripts that comprised open reading frames with known associated functions, and that harbored intact functional domains. Using the above criteria, we identified and validated by RT-PCR nine in-frame fusion transcripts in the index cases (Figs. 5a-i  and Supplementary Table  19 ), though none was recurrent in our series.
9 Validation of significantly differentially expressed genes between spindle and non-spindle MBCs identified by microarray-based gene expression analysis was performed using RNA-sequencing data. For each gene, normalized expression value is plotted for each MBC, grouped by histologic subtype. p-values were calculated from the differential expression analysis using limma  46  (see Methods) These data suggest that although MBCs are driven by a pathognomonic gene fusion or a pathognomonic expressed mutation in previously described cancer genes  [29] [30] [31]  , some of these genetic alterations may play a role in individual MBCs.
RNA-sequencing and fusion transcript identification RNA-sequencing (2 × 54 bp) was performed for all 17 MBCs included in this study using the standard Illumina mRNA library protocol on a Genome Analyzer II (Illumina) as previously described. 42 deFuse  26  and Chimer-aScan  27  were used to identify mate-pairs supporting novel chimeric transcripts as previously described  42  (Supplementary Methods). Candidates that resulted in open reading frames were annotated using OncoFuse. 44 ominated in-frame fusion gene candidates, candidates identified by both deFuse and ChimeraScan, as well as those with known associated functions, and those that harbored intact functional domains were prioritized for validation in the index cases by reverse transcription (RT)-PCR (Supplementary Table  22  and Supplementary Methods).
ACKNOWLEDGEMENTS The authors acknowledge  Leticia Fuhrmann  for her assistance with retrieving clinical information. This study was funded in part by  Breast Cancer Research Foundation (BCRF). S. P. is funded by  Swiss National Science Foundation  (Ambizione grant number  PZ00P3_168165 ). R. N. is funded by a  Breast Cancer   Campaign Career Development Fellowship  (2011MaySF01). Research reported in this publication was supported in part by a  Cancer Center Support  Grant of the  National Institutes of Health/National Cancer Institute  (Grant No. P30CA008748 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Material and Methods Participants. Information about the goals of the prospective longitudinal AlphaLewyMA study is freely available on the Clinical Trials web site (http://clinicaltrials. gov/ct2/show/NCT01876459). Briefly, the primary end point was to assess synuclein in the cerebrospinal fluid, and the secondary end point, which concerned the present study, was to create biomarker for DLB and AD using MRI. One hundred forty-four patients with either DLB or AD were consecutively recruited from the Memory Resources and Research Center of the University Hospital of Strasbourg, France, together with 22 elderly healthy controls. Nine participants were excluded due to motion during the MRI acquisition (n = 9). The remaining 135 patients were classified according to their diagnosis and the level of their cognitive deficit.
Consequently, the study comprised 54 patients with pro-DLB (pro-DLB group), 15 patients with DLB at the dementia stage (mild-DLB group), 16 patients with pro-AD (pro-AD group), 28 patients with AD at the dementia stage (mild-AD group), and 22 healthy elderly controls (HC group). Demographic data are presented in Table  1. Patients presenting both DLB and AD clinical features were excluded from the analysis. The five groups were examined by clinicians with expertise (tertiary center) in dementia to perform a complete anamnesis and medical examination. Using the Unified Parkinson's Disease Rating Scale (UPDRS) III score  38  , akinesia, rigidity, and tremor at rest were rated from 0 to 4 (0: no symptoms to 4: serious impairment). Fluctuations were assessed with the Mayo Clinic Fluctuations scale (patients with a score higher than or equal to two were considered as having fluctuations) and the Newcastle-upon-Tyne Clinician Assessment of Fluctuation scale.
Data acquisition. A 3D MPRAGE T1-weighted image was acquired on a Siemens Verio 3 T scanner equipped with a 32-channel head coil (Siemens, Erlangen Germany). Parameters were: sagittal orientation; repetition time = 1900 ms; echo time = 2. 53 ms; inversion time = 900 ms; flip angle = 9°; imaging matrix 192 × 192 × 176; 1 mm 3 isotropic voxel; acquisition time = 7 min 38 s. The image was acquired such that the axial slice orientation was aligned with the AC-PC line. Data processing. Images were processed using SPM8 (Welcome Department of Cognitive Neurology, London, UK). According to the algorithm of the New Segment toolbox of SPM8, images were first segmented into five tissue probability maps in the native space. Two GM DARTEL templates were then computed from GM and WM probability maps of either a subset that included the pro-DLB, pro-AD and HC groups, or another subset that included the mild-DLB, mild-AD and HC groups.
Statistical analysis. Patients with either MCI or dementia were analyzed separately, i. e. a first set of analyses compared the pro-DLB, pro-AD and HC groups, whereas another compared the mild-DLB, mild-AD and HC groups. Analyses were performed on Matlab (R2014b, Mathworks, Natick, MA). The distribution of gender and age values between groups was assessed by chi-squared tests and a one-way ANOVA, respectively. Prior to ANOVA, homoscedasticity and normality of the distribution of age values were verified by Levene's test and Lilliefors tests to ensure that our conditions really met the assumptions of ANOVA as a parametric test. Post-hoc analyses were performed using Tukey-Kramer multi-comparison test. Using the randomize function of FSL 5. 0 (FMRIB Analysis Group, Oxford, UK), non-parametric permutation tests with threshold-free cluster enhancement were performed to compare GM and WM volumes between groups, by running 5,000 permutations with variance smoothing of 8 mm.
Acknowledgements This study was funded by  Appel à Projet Interne (API)  of the  University Hospital of Strasbourg ,  Alsace Alzheimer 67 ,  Fondation Université de Strasbourg  and-AG2R la Mondiale and  Famille Jean Amrhein-, Projet Hospitalier de Recherche Clinique (PHRC) inter-régional  ( IDRCB 2012-A00992-41 ). The authors would like to thank  Dr Julien Lamy  for helpful suggestions,  Mélanie Stackfleth ,  Anne Botzung  and  Laetitia Berly  for help with organising the study,  Timothée Albasser ,  Mathias Bilger ,  Laure Di Bitonto ,  Emmanuelle Ehrhard ,  Geraldine Heim ,  Jennifer Kemp ,  Catherine Kleitz ,  Nadine Longato ,  Laetitia Monjoin ,  Clélie Philipps  and  Natacha Vogt  for conducting neuropsychological assessments, and  Paulo Loureiro de Sousa ,  Corinne Marrer ,  Stéphane Kremer , and  Daniel Gounot  for performing MRI.
The flakes were continuously fed into the reactor. The ratio between contaminated and non-contaminated flakes was approximately 1:22. Samples were taken at the outlet of the reactor at regular intervals. The green flakes were separated from the white flakes and the evolution of the fraction of green flakes with time (residence time distribution curve) was determined by weighing. The green flakes were then analysed for their residual concentrations of the applied surrogates. The Panel noted that decontamination efficiencies, calculated only on the basis of residual surrogates in contaminated (green coloured) flakes could be overestimated. In fact, based on EFSA CEF Panel (2011), cross-contamination 3 by transfer of contaminants from green to white flakes does occur. Therefore to take into account the cross-contamination phenomenon, the following considerations and assumptions were made: • The mass fraction of green to white flakes at various residence time points was derived from the data provided.
Statistical analysis The exact binomial test established confidence intervals (CI) with a 95% confidence level. The Chi-square, Fisher's or Fisher-Freeman-Halton exact tests were used to compare percentages of positivity among categories of the same independent variables and also the total prevalence of each agent. Correlation between pathogens was also calculated. A P-value < 0. 05 was considered as statistically significant. For factors with significant results, odds ratio (OR) was presented. Analyses were performed with SPSS® 23 software for Windows and Epi Info™ 7. 1. 5. 2 software from Centers for Disease Control and Prevention.
Funding This work was supported through funds received from (i) the  GHTM -UID/Multi/ 04413/2013 , (ii) the  EU  grant  FP7-261504  EDENext (http://www. edenext. eu),(iii) the  European Virus Archive goes Global (EVAg)  project in the European Union's  Horizon 2020 research and innovation programme  under grant agreement No  653316  (http://global. european-virus-archive. com/). CM has the support of the  Portuguese Ministry of Education and Science (via Fundação para a Ciência e a Tecnologia) , through an  Investigator Starting Grant   IF/01302/2015. The work of  C. Maia  and  R. N. Charrel  were done under the frame of EurNegVec COST Action TD1303.
Of the obtained 500 μL of concentrated CM, 50 μL were loaded onto a polyacrylamide gel (4-20% mini-Protean TGX gel, Bio-Rad 456-1096) and the proteins separated by electrophoresis were stained with EZ Blue staining reagent (Sigma-Aldrich G1041). After elution from the gel, peptides were obtained by trypsin hydrolysis, separated by HPLC (Ultimate 3000 Rapid Separation LC Systems, Dionex), and sequenced by tandem mass spectrometry (Q-Exactive Thermofischer). Secreted proteins were identified using the Swiss Prot data bank (http://web. expasy. org/docs/swiss-prot_ guideline. html) and analyzed using the Ingenuity Pathway Analysis software (https://www. qiagenbioinformatics. com/ products/ingenuity-pathway-analysis/).
Then complementary RNA was synthesized, amplified, and labeled with cyanine 3 dye according to the manufacturer's protocols. Cyanine 3-labeled cRNA (1. 65 μg) was fragmented and hybridized to the Agilent Whole Mouse Genome Oligo Microarray 4x44k at 65 °C for 17 hours. After washing, fluorescence intensity at each spot was assayed using a G2565BA Microarray Scanner (Agilent). After extraction with Feature Extraction Software 9. 5. 3 (Agilent), data were normalized (background subtraction and quantile normalization) using AgiND library developed under R software for Agilent microarray data normalization and visualization. A fold change ratio (each lesioned hippocampus against pooled control hippocampus) was calculated for every spot. Data are available on the ArrayExpress database (accession number E-MEXP-2682).
1155/2017/1478606 for assay IDs). For each experiment, 25 ng of previously prepared hippocampus cDNA were used. Samples were run in duplicates and analyzed with the 7500 Software v2. 0 (Applied Biosystems). Relative expression levels were determined according to the ΔΔCt method, the Gapdh gene serving as endogenous control for normalization. Receptor expression in human OE-MSCs was assessed with the same protocol (see Supplementary Table  2  for assay IDs). In this case, data were normalized using the human housekeeping gene ABELSON, as previously described  [33]. For each OE-MSC donor, RNA extractions were performed from three independent cultures and the reported values are the mean of these three independent experiments, each performed in duplicate. 2. 7. Tissue Processing. One month after surgery, unilaterally injured mice (n = 3) were deeply anesthetized (sodium pentobarbital, i.
Then, slices were rinsed (3 × 5 min) in PBS and incubated for 90 min at RT with cross-adsorbed Alexa-Fluor 488-or 594-conjugated anti-rabbit or anti-mouse secondary antibodies (1/500, Jackson Immunoresearch, West Grove, PA, USA) in the dark. After several washes in PBS, slices were counterstained with 0. 5 μg/mL Hoechst blue (#33342, Sigma-Aldrich) for 30 min at RT and mounted with ProLong Gold Antifade reagent (Invitrogen/Life Technologies). Images were acquired with an inverted Axio Observer microscope (Zeiss, Jena, Germany) equipped with DAPI, FITC, and rhodamine epifluorescence filters, using the mosaic mode of the Axiovision software (Zeiss). For cytochemistry on the BBB model, OE-MSC transmigration was carried out on the 12-well plate insert filters and cells were fixed for 15 min in 4% paraformaldehyde.