dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical analysis Statistical analyses were carried out using the XLSTAT-Pro 1 2014. 5. 03 software (Addinsoft, Paris, France) and the normality of data was tested using a Shapiro-Wilk test. The comparison of OsHV-1 DNA amounts in the mantle between the two batches was performed using a parametric t-test or a non-parametric Mann-Whitney test if normal distribution could not be demonstrated. Flow cytrometry data were compared between the two conditions (haemocytes from OsHV-1 infected and ASW injected oysters) by a two-way analysis of variance (ANOVA) followed by a Tukey post-test.
Chemokine was freshly nitrated for each experiment and all chemokines were purchased from Almac, UK. The exact residues modified by peroxynitrite were identified by mass spectrometry. Tryptic digestion was performed prior to LC-MS/MS and the data were analysed using Mascot (Matrix Science) as described earlier  39. Immunofluorescence. Formalin-fixed paraffin-embedded (FFPE) tissue sections from patient biopsies diagnosed with ATN, 1 week post-kidney transplant were dewaxed (Research Ethics Committee approval, Ref. -11/NE/0352). Antigen retrieval was carried out using citrate buffer (pH6) for 2 mins. Sections were blocked for 30 mins with 20% normal goat serum. They were stained sequentially, with primary antibody overnight at 4 °C and secondary for 2 hours at room temperature. Anti-nitrotyrosine polyclonal (1/500, Millipore) was detected using a FITC conjugated secondary antibody (1/300, Sigma), and anti-CCL2 polyclonal (1/500, Abcam) was detected using a Dylight-550 conjugated secondary antibody (1/100, Immunoreagents).
Acknowledgements This work was supported by the  MRC  and the  NIHR Biomedical Research Centre for Ageing  and grants from  FP7-MC-ITN (POSAT ,  606979 ), the  Agence Nationale de la Recherche  ( ANR-NT05-4-41968-Chemoglycan ) and used the platforms of the  Grenoble Instruct Centre (ISBG ;  UMS 3518 CNRS-CEA-UJF-EMBL ) with support from  FRISBI  ( ANR-10-INSB-05-02 ) and  GRAL  ( ANR-10-LABX-49-01 ) within the  Grenoble Partnership for Structural Biology  (PSB). Radiation work was completed with the help of  Jim Lloyd  and  Elizabeth Howell ,  Medical Physics department, RVI, Newcastle. Mass spectrometry was performed by  Dr Joe Gray ,  Pinnacle Laboratory, Newcastle University. Murine air pouch models were performed with the assistance of  Mr Chris Huggins ,  Comparative Biology Centre, Newcastle University.
Repeated sampling of the same bat populations would be needed to examine potential seasonal variations in virus transmission between hosts and locations. A Bayesian Markov Chain Monte Carlo coalescent analysis was performed with 31 sequences obtained in this study (GenBank accession numbers KY575644-KY575674) and 83 reference AstV RdRp partial nucleotide sequences. Sequences (395 bp) were aligned using CLC Sequence Viewer version 7. 7. 1 (CLC Bio, Aarhus, Denmark). The coalescent analysis was performed with the program BEAST 1. 8. 4,  11 with the general time-reversible evolutionary model, an estimation of the proportion of invariable sites (I) and of the nucleotide heterogeneity of substitution rates (α), as selected by Model Generator 0. 85. 12 A strict molecular clock and a constant population size were selected.
ACKNOWLEDGEMENTS Malalanirina Rakotomanga  and  Andrianiaina Randrenjarison  are thanked for their assistance in the field. Research permits for animal sampling were issued by the  Direction du Système des Aires Protégées, Direction Générale de l'Environnement et des Forêts , and  Madagascar National Parks , following regulations of Malagasy national authorities (permit NO  238/14/MEEF/SG/ DGF/DCB. SAP/SCB  and  268/14/MEEF/SG/DGF/DCB. SAP/SCB ). Field research was funded by the  'Fond Européen de Développement Régional: ParamyxOI'  ( Programme Opérationnel de Coopération Territoriale NO 33857 ), and molecular analyses were funded by the  Université de La Réunion. BR's post-doctoral fellowship was supported by the  'Run Emerge' European Union 's  Seventh Framework Program  ( FP7/2007-2013; Grant agreement NO 263958 ), the  'Fonds de Coopération Régionale, Prefecture de La Réunion ' and The  Field Museum of Natural History, Chicago , through the  Ralph and Marian Falk Medical Research Trust.
Ethics statements French National Agency regulating data protection (Commission Nationale de l'Informatique et des Libertes) approved this observational study (DR-2013-041; N˚912650). All data were recorded anonymously through the approved database. As diagnosis and treatment strategy followed the international or national guidelines (of each country) there is no ethical concern on treatment and diagnosis. Patients (or parents or legal guardians of children) gave their informed oral or written consent allowing examinations on their samples and publication of anonymized data on clinical findings, treatment received, clinical outcome and laboratory examinations.
Data collection From 2008 through 2012 data were collected in a French nationwide centralized referral treatment program as reported elsewhere  [12]. Briefly, these data were collected by experts providing treatment advice to physicians attending patients with leishmaniasis in France. Expert advice was part of normal medical process and followed the national guidelines  [2]. Demographic and clinical data were obtained from treating physicians through a standardized case report form. After at least 45 days after the treatment advice has been provided, the attending physician was contacted and asked to provide follow-up information, using a standardized form, regarding the identification of the infecting Leishmania species, treatment currently administered, treatment outcome, and adverse events.
From 2012 through 2016, data were collected in the European LeishMan ("Leishmaniasis management") database, a multicentre multinational surveillance project on cutaneous and mucosal leishmaniasis. The consortium gathers 17 experts from 12 institutions in 7 European countries (France, Switzerland, United-Kingdom, Belgium, Netherlands, Germany and Spain) who aim at improving the management of leishmaniasis through harmonization of medical practices and collection of data in an international surveillance system  [13]. Demographic, clinical and biological data were assessed in an electronic case report form and documented before and after treatment. Treatment schedule was left at the discretion of the attending physician, unless he/she explicitly required advice on this point from the expert.
Characteristics of patients From 2008 through 2016, data from 45 patients who had received at least one infusion of L-AmB for TL were entered into the databases. Two patients had no-follow-up and were excluded from the analysis. The characteristics of 43 travelers returning from 18 different countries are shown in Table  1. Twenty nine centers from 3 countries (26 in France, 2 in Switzerland, 1 in Germany) participated to the study. Leishmaniasis was mainly acquired in the Old World (9 in Europe, 9 in Maghreb, 6 in sub-Saharan Africa, 3 in Middle East, 1 in India). 15 patients were infected in the New World (10 in French Guiana, 3 in Bolivia, 1 in Brazil, 1 in Peru). Median age of the cohort (which comprised 6 children aged from 1 to 12 years) was 55 years for adults. Seven patients (19% of adults) had prior cardiovascular history.
Data were acquired using FAC SCalibur, LSR II, Accuri C6 (all from BD), or MAC SQuant (Miltenyi Biotec) flow cytometers. FITC channel was used for analysis of GFP or YFP expression (Fig. 2  A and Figs. S2  and S3 ). Data were analyzed with FlowJo software (Tree Star). Dead cells (identified by staining with propidium iodide or LIVE/DEAD Fixable Dead Cell Stains; Invitrogen) were not included in the analysis. For complete blood analysis (Fig. S2 ), total red blood cells, white blood cells, and platelets were counted using the Abbott Cell-Dyn 3500 automated hematology analyzer. cLP CLP was performed as described previously  (Piliponsky et al. , 2012). In brief, mice were deeply anesthetized by intramuscular injection of 100 mg/kg ketamine and 20 mg/kg xylazine, the cecum was exposed by a 1-to 2-cm midline incision on the anterior abdomen, and ligation of the distal half of the cecum and single puncture (with a 22-gauge needle) of the ligated segment were performed.
Measurements of MPo and MPo activity MPO was quantified from peritoneal lavage fluid by ELI SA according to the manufacturer's instructions (R&D Systems). Bioluminescent imaging of MPO activity was performed 6 h after LPS injection  (Zhang et al. , 2013). Mice were anesthetized (isoflurane inhalation), and 10 min after injection of luminol-R (a mixture of Luminol [200 mg/kg; Sigma-Aldrich] and near-infrared quantum dots [QD800 from Life Sciences; 100 pmol]; 100 µl each i. p. + i. v. ), animals were sacrificed and organs were sampled for imaging (2 min; open filter). Imaging and analysis was performed using an IVIS Spectrum with LivingImage software (Xenogen Product from PerkinElmer). We controlled for the in vivo distribution of luminol-R by fluorescent imaging of QD800 particles (ex-citation 745 nm, emission 800 nm) and found no difference in fluorescence intensity between organs from LPS-treated neutrophil-sufficient and neutrophil-depleted mice or LPStreated WT and Mpo -/-mice.
We thank  Irving Weissman  and  Clifford Lowell  for sharing MRP8-Cre mice and  Gerard Eberl  for ROSA-EYFP reporter mice. We thank members of the  Centre de Gnotobiologie de l'Institut Pasteur Murine, Institut Pasteur , for experiments with GF mice and animal husbandry. We also thank all members of the  Galli and Bruhns laboratories  for discussions and technical assistance. L. L. Reber acknowledges support from the  National Institutes of Health  (grant  K99AI110645 ), the  European Commission  ( Marie Skłodowska-Curie Individual Fellowship   H2020-MSCA-IF-2014 656086 ), and the  Institut National de la Santé et de la Recherche Médicale (INS ERM). C. M. Gillis  was supported partly by a stipend from the  Pasteur-Paris University (PPU)   International PhD program  and the  Institut Carnot Pasteur Maladies Infectieuses , and partly by the  Balsan company , as well as the  European Research Council Seventh Framework Programme  ( ERC-2013-CoG 616050 ).
P. Starkl was supported by a  Max Kade Fellowship  of the  Max Kade Foundation  and the  Austrian Academy of Sciences  and a  Schroedinger Fellowship of the Austrian Science Fund (FWF ;  J3399-B21 ) and is supported by a  European   Commission Marie Skłodowska-Curie Individual Fellowship  ( H2020-MSCA-IF-2014 655153 ). F. Jönsson  is an employee of the  Centre National de la Recherche Scientifique. R. Sibilano  was supported by the  Lucile Packard Foundation for Children's Health  and the  Stanford University National Institutes of Health/National Center for Research Resources   CTSA award  (number  UL1 RR025744 ). T. Marichal was supported by the  European Commission Marie Curie   International Outgoing Fellowship for Career Development  ( 299954 ), is supported by the  Acteria Foundation , and is a Research Associate of the  Fonds De La Recherche Scientifique-FNRS.
We next determined the tumour take and tumour growth rates of sorted CSC-like cells and non-CSCs in a xenograft model using immunodeficient NOD scid gamma (NSG) mice. To this end, we transduced CSC-like cells and non-CSCs with lentiviral vectors that conferred co-expression of the red fluorescent protein tdTomato to allow non-invasive tumour imaging, and of influenza virus matrix protein M1 (FluM1) as surrogate tumour-specific antigen (Supplementary Figure  S2 ). Lentivirally transduced CSC-like cells and non-CSCs were indistinguishable from the corresponding parental cell lines with respect to phenotype, morphology and long-term stability in culture (data not shown). Upon injection into NSG mice, CD44 hi CD24 lo CSC-like cells showed a striking potential to form tumours in 100% of treated animals, at numbers as low as 1 × 10 3 CSC-like cells per mouse, as evidenced by in vivo imaging of tdTomato fluorescence as well as caliper measurements of palpable tumours (Figure  2c , Supplementary Figure  S3 ).
Prepared slides were imaged and analysed using a Zeiss AxioVert fluorescence microscope (Zeiss, Cambridge, UK). Images were processed with Photoshop 6. 0 (Adobe, San Jose, CA, USA). For video microscopy, target cells were incubated overnight in Ibidi chamber slides (Martinsried, Germany) coated with fibronectin (Millipore). For intracellular Ca 2+ measurements, CD8 + T cells were loaded with 1 μM Fura-2/ AM (Invitrogen) and analysed using a DMI 6000B microscope (Leica Microsystems). Cells were illuminated every 10 s with a 300 W xenon lamp by using 340/10 nm and 380/10 nm excitation filters. Emission at 510 nm was captured using a Cool Snap HQ2 camera (Roper, Tucson, AZ, USA) with Metafluor software (Molecular Devices, Sunnyvale, CA, USA). Ratio measurements were performed with Imaris 8. 1 imaging software (Oxford Instruments, Abingdon, UK).
ACKNOWLEDGEMENTS We would like to thank  Robert Weinberg  for providing HLMER cells;  James Riley  and  Mai Ping Tan  for plasmids;  Andrew Thomas  for recombinant FluM1 protein and HLA-A2 tetramers;  Fariba Navid  for hu14. 18K322Aantibodies;  Daniel Olive  for BTN3A blocking antibodies;  Hassan Jomaa  for synthetic HMB-PP;  Nooshin Tabatabaei-Zavareh  for custom-made γδ T-cell isolation kits;  Catherine Naseriyan ,  Kelly Miners  and  Kristin Ladell  for cell sorting;  Aled Clayton  for help with confocal microscopy;  Tamsin Dockree ,  Chia-Te Liao  and  Lisa Starick  for help with lentiviral constructs;  Emily Colbeck ,  Emma Jones  and  Anwen Williams  for help with histology;  Garry Dolton ,  Ellyn Hughes  and  Emma Kempshall  for help with animal studies; and the  Cellular and Tissular Imaging Core Facility of Nantes University  (MicroPICell) and  Lola Boutin  for help with video microscopy and calcium experiments.
This research was supported by the  Wales Cancer Research Centre  and the  Cardiff CR-UK Centre Development Fund; Cancer Research UK  grants  C28524/A9497 ,  C42921/ A13823  and  C16731/A21200 ;  Institut National de la Santé et de la Recherche Médicale (INSERM) ;  Centre National de la Recherche Scientifique (CNRS) ;  Université de Nantes ;  Institut National du Cancer (INCa   PLBIO 2014-155 ) and  Investissements d'Avenir (Agence Nationale de la Recherche - Programme Laboratoires d'Excellence Immunotherapy Graft Oncology ; # ANR-11-LABX-0016-01 );  Wilhelm Sander-Stiftung  grant  2013. 907. 1 ;Tenovus PhD Studentships to H-CC and LP; a  Government Scholarship for Study Abroad  from the  Taiwanese Ministry of Education  (H-CC); an  Erasmus+ Traineeship  (YS); and a  Cardiff Incoming Visiting Fellowship  (TH).
Analysis of oxytetracycline A high pressure liquid chromatography (HPLC) method with ultraviolet detection was used for analysis of oxytetracycline concentrations in serum, exudate and transudate  (Brentnall et al. , 2012). All reagents were HPLC grade and obtained from Sigma-Aldrich Chemicals (Poole, Dorset, UK). Chromatographic data were analysed using Chromeleon TM Version 6. 80 (Dionex Corporation) and concentrations of oxytetracycline were calculated using peak area ratios. Standards were prepared by spiking blank serum, exudate and transudate with oxytetracycline, using eight concentrations over the range 0. 1 to 25µg/mL (serum) and 0. 1 to 5µg/mL (exudate and transudate). They were run with every assay to evaluate linearity and reproducibility. For linearity r 2 was >0. 98. The lower limit of quantification (LLOQ) for oxytetracycline in all three fluids was 0.
Pharmacokinetic analyses Oxytetracycline concentration-time data in serum, exudate and transudate in individual calves were analysed using the WinNonlin® regression programme (version 5. 2, Pharsight Corporation, Mountain View, California, USA). Data for each fluid were submitted to noncompartmental analysis using the statistical moment approach described by  (Yamaoka et al. , 1978). The linear trapezoidal rule was used to calculate AUC values and area under the first moment curve (AUMC). The mean residence time (MRT) was determined as AUMC/AUC.
PK-PD modelling of in vitro time-kill data For six isolates each of M. haemolytica and P. multocida growth inhibition curves over 24h were determined in two matrices, MHB and calf serum, as previously described  (Lees et al. , 2015). Ratios of AUC0-24h/MIC were calculated for each of the six isolates of the two organisms at each of the five oxytetracycline concentrations tested (from 0. 25 to 4xMIC multiples). AUC0-24h values were computed in terms of MIC multiples (vide infra). The data were modelled to the sigmoidal Emax equation (Equation  3 ) using the non-linear regression WinNonlin® programme: 𝐸 = 𝐸 0 + 𝐸 𝑚𝑎𝑥 × 𝑋 𝑁 𝐸𝐶 50 𝑁 + 𝑋 𝑁. ( 3 ) where E0 is the bacterial growth after 24h incubation in the absence of oxytetracycline (control samples), expressed as log10cfu/mL subtracted from the initial inoculum log10 cfu/mL; Emax is the maximum antimicrobial growth inhibition determined as the change in log10cfu/mL after 24h incubation with oxytetracycline; EC50 is the AUC0-24h/MIC value providing 50% of the maximum antibacterial effect; X is the predictive variable (expressed as AUC0-24h/MIC) and N is the Hill coefficient, which describes the slope of the AUC0-24h/MICeffect curve.
Dose (loading dose 48h ) = 1 1-exp (-𝐾 10 ×48) × 𝐶𝑙 (48ℎ) × Κ 𝑃𝐷 × 𝑀𝐼𝐶 𝑑𝑖𝑠𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 𝐹 × 𝑓 𝑢 (8) Monte Carlo simulation for the two approaches to dose estimation: Dosages were computed using Monte Carlo simulations in Oracle Crystal Ball (Oracle Corporation, Redwood Shores, CA, USA). The maintenance dose (per 48h) was calculated using equation (  5 ) and the loading dose (for 48h interval) was calculated using equation 8. Loading and maintenance doses were determined to achieve bacteriostatic and bactericidal responses. The probabilistic approach took into account the different distribution of variables embedded in Equations 5 and 8. The average point estimate of the serum κPD was calculated from the data obtained with four isolates of each species, but variability in κPD was not included in the Monte Carlo simulation, as the number of isolates was small and inter-isolate variability was low.
Dosage prediction Predicted (TAR) doses for oxytetracycline were calculated using scientific literature values for oxytetracycline MIC distributions together with data from this study for PK variables (Cl/F and fu) and PK-PD breakpoints (AUC0-24h/MICe). Fifty and 90% TAR dosages were calculated for steady state and for single doses with a duration of action of 48h in both cases. All doses based on oxytetracycline MICs in serum were some 25-fold greater than doses based on MICs measured by the CLSI method in broth. For example, for single dosing and a period of 48h the 90% TAR dosages for a bactericidal action (serum first, broth second) were 452 and 17. 9 mg/kg (M. haemolytica) and 1,523 and 55. 6 mg/kg (P. multocida). Despite these considerations, it should be noted that oxytetracycline is usually classified as a bacteriostat and it is therefore assumed that efficacy will generally require the support of the body's natural defence mechanisms.
Statistical analysis Data are represented as mean ± SEM. Statistical significance was determined using Log Rank test (survival curves), unpaired two-tail Student's t test (on log10 values of CFU counts, and log2 gene expression data), or ANOVA with Bonferroni posttest as specified in the figure legends (neutrophil counts, Caspase-1 activity) using Prism software (GraphPad Software Inc). Data were considered significant when P<0. 05 ( Ã ), P<0. 01 ( ÃÃ ), or P<0. 001 ( ÃÃÃ ). lyz:dsRed zebrafish embryos were injected with Sept15 morpholino and infected at 3 dpf in the HBV with a low dose of GFP-S. flexneri M90T and imaged every 2 min from 20 mpi (t = 0 on the movie) to 20 h 30 mpi (t = 20 h on the movie) using confocal microscopy. S6 and S7 Videos were acquired at the same time. Note that at the beginning of this movie, neutrophil behaviour from Sept15 morphant is similar to that of Ctrl morphant: neutrophils are recruited by 1 hpi and interact with S.
Funding: ARW is supported by a  Medical Research Council  PhD studentship. VT is supported by a  Marie Skłodowska-Curie Fellowship  ( H2020-MSCA-IF-2015 -700088 ). Work in the Mostowy laboratory is supported by a  Wellcome Trust   Research Career Development Fellowship  ( WT097411MA ) and the  Lister Institute of Preventive Medicine. The funders had no role in neutrophil death. link between septins and inflammation, and highlight the cytoskeleton as a structural determinant of host defence. study design, data collection and analysis, decision to publish, or preparation of the manuscript.
13 hese data, as well as recent data with secukinumab,  14, 15  another anti-IL-17A monoclonal antibody, provide evidence that reaching PASI 90 is now an achievable treatment outcome for a majority of patients. ] [22]  The current study, IXORA-S, is the first head-to-head trial including ixekizumab and ustekinumab over 52 weeks, with a primary objective of comparing PASI 90 at week 12. The week 12 primary end point data is presented here. Additionally, due to the dosing schedule of ustekinumab, we also present efficacy and safety results up to week 24 for a more accurate comparison between the two treatments. Safety and efficacy data from week 52 will be disclosed at a future date, as the study is still ongoing.
Study design This 52-week, phase IIIb, multicentre, controlled, double-blind, parallel-group trial (IXORA-S, NCT02561806) was conducted at 51 sites across 13 countries. Patients were randomized (1 : 1) via an interactive web-response system to receive either ixekizumab or ustekinumab. Randomization was stratified by study centre and patient weight (≤ 100Á0 kg vs. > 100Á0 kg). The clinical trial details can be accessed at www. clinicaltrials. gov. During the induction period (weeks 0-12), patients randomized to ixekizumab received two subcutaneous (SC) injections of ixekizumab 80 mg (160 mg total) at week 0, followed by one SC injection of ixekizumab 80 mg every 2 weeks through week 12, and 80 mg every 4 weeks thereafter (Fig. 1 ). Patients randomized to ustekinumab were dosed at weeks 0, 4, 16, 28 and 40, in accordance with the label, with patients weighing ≤ 100Á0 kg receiving 45 mg SC injections and patients weighing > 100Á0 kg receiving 90 mg SC injections.
Statistical analyses Patients were analysed according to the treatment they were assigned at randomization (intention-to-treat population). The primary-analysis model was a logistic regression for the PASI 90 response end point after 12 weeks of treatment, with terms for treatment group, weight and geographical region. Missing data were imputed via nonresponder imputation (NRI), assuming that patients without data had no response. This primary logistic regression model used 97Á5% confidence intervals to estimate the difference in proportions between ixekizumab and ustekinumab (Appendix S2; see Supporting Information). The eight key secondary end point comparisons (for points i-viii above) were assessed via logistic regression with NRI for binary end points, or ANCOVA with modified baseline observation carried forward for continuous end points.
Logistic regression models included terms for treatment group, weight and geographical region. ANCOVA models included terms for baseline value, treatment group, weight and geographical region. To avoid inflation of type I error (i. e. to limit the chance of an overall false-positive result) at the 5% level, the Hommel procedure was used to adjust P-values for key secondary end points at week 12. 25  Comparisons of secondary outcomes over time were made using Fisher's exact test, after data were imputed via the NRI method. Safety analyses were performed in patients who received at least one dose of the study treatment (safety population). Safety events were analysed using Fisher's exact test. P-values were considered statistically significant at the 5% alpha level and confidence intervals were, unless otherwise noted, at the 95% level.