dataesr/scientific-paragraphs-categorization huggingface dataset:
Search strategy The search was performed by one author (MN) with the assistance of an information specialist (OL). Electronic databases MEDLINE via PubMed, CENTRAL, LILACS and EMBASE were searched on 12 November 2014, with no limitations on dates or language. To search for studies of mTOR inhibitors, the following keywords were used: "mTOR inhibitor", "sirolimus", "everolimus", "temsirolimus" and "deforolimus". To search for all vascular anomalies, the following keywords were used: "angioma", hemangioma", "Kasabach-Merritt", "hemangioendothelioma", "glomangioma", "vascular", "venous", "capillary", "lymphatic", "lymphedema", "lymphangioma" and "arteriovenous".
Data extraction For each selected report, 2 authors (MN, AM) independently extracted information on the first author, publication year, journal, country/site, study design, characteristics of patients, type of vascular anomaly, number of lesions, associated complications, type of mTOR inhibitor, efficacy and side-effects, cointerventions and follow-up. Any disagreements were resolved by discussion. A data table was established for each patient. The extraction table was developed by 3 authors who are dermatologists familiar with vascular anomalies (MN, GL, AM). For missing data, the first author was contacted when possible.
Main results The aim of this systematic review was to assess the efficacy and safety of mTOR inhibitors for vascular anomalies in children and adults. Data were assessed for 84 patients; all children < 18 years. Sirolimus was the most frequent mTOR inhibitor used and was rapidly efficient in all cases, at a median of 2 weeks 95% CI (1-10 weeks). Sirolimus was well tolerated, the main side-effect being mouth sores, which led to treatment withdrawal in one case.
Tissue preparation for organ bath studies Bronchial rings were suspended horizontally on tissue hooks in an organ bath containing 5 ml of PSS (gassed with 95% O 2 , 5% CO 2 ) and maintained at 37 °C (pH 7. 40). Each preparation was connected to a force displacement transducer (it1, Emka Technologies, Paris, France). Isometric tension was measured and processed with a computerized system running IOX software (v2. 4. 2) and analyzed with Datanalyst (v2. 1. 0) software (EMKA technologies, Paris, France). Bronchi were suspended with an initial tension of 1. 5 g  [15]  and equilibrated for 60 min. During the equilibration period, the bath's PPS was changed after 10, 20 and 30 min. At the end of this period, bronchi were contracted with acetylcholine (3. 10 -3 M) to determine the maximal tone (Emax) developed during contraction in the absence of any treatment or pretreatment.
Drugs ACh, indomethacin, L-NAME, tetrodotoxin, Gd 3+ , nicardipine, capsazepine, and calphostin C were purchased from Sigma-Aldrich (St. Louis, MO, USA), tertiapin was bought from Bachem (Voisin le Bretonneux, France),   4 ), bronchial tone at rest immediately after the end of cyclic stretching; (5), post-stretching bronchial tone within 10 min following the cyclic stretching period; (6) maximal bronchial contraction in response to 3 mM ACh after cyclic stretching. In the control group, bronchial tone did not change significantly between points 4 and 6 (data not shown)  (20)  and SB-203580 was supplied by Calbiochem (San Diego, CA, USA). MK476 came from Merck Sharp & Chibret (Paris, France). Y27632 was purchased from Alexis Biochemicals (San Diego, CA, USA). All drugs (other than indomethacin, nicardipine and SB-203580) were dissolved in distilled water.
The results were analyzed using Student's t test for paired and normally distributed data or using a Wilcoxon matched-pairs signed rank test if the data were not normally distributed. The standardized effect size |d| for the difference between the means was calculated in order to determine whether the observed effect of each pretreatment was small (|d| ≥ 0. 20), medium (|d| ≥ 0. 50) or large (|d| ≥ 0. 80), according to Cohen's conventions  [20]. The 95% confidence interval (CI) for d was calculated as a measure of the uncertainty with regard to the true effect of each pretreatment. A P value < 0. 05 was considered to be statistically significant. Data analysis and statistical tests were performed using Statistica'99 software, version 5. 5, StatSoft, Tulsa, OK, USA).
Three-dimensional spheroid cell culture MiaPaCa-2 cells (5×10 3 /well) were seeded in 96-well plates containing Matrigel (Corning). The culture medium (containing appropriate concentration of Met or Mito-Met 10 ) was replaced every two days. At days 3, 7, and 14 the images were acquired using a Nikon Eclipse Ti inverted microscope (Nikon Inc. , NY). Spheroid-forming cells were counted using the Nikon NIS Elements imaging software.
Cytotoxicity assay To determine the cytotoxicity of Mito-Met analogs and other TPP + -conjugated compounds, we used the Sytox Green-based assay as described previously  (16). MiaPaCa-2 cells were treated for 24 h, and dead cells were monitored in real time in the presence of 200 nM Sytox Green (Invitrogen) under an atmosphere of 5% CO 2 :95% air at 37°C. Data are represented as a percentage of dead cells after normalization to total cell number (measured with Sytox Green after a 3 h treatment with 0. 065% Triton X-100) for each group.
Cell cycle analysis PANC1 cells (5×10 5 ) were seeded into 35 mm dishes and immediately treated with 10 mM Met or 10 μM Mito-Met 10 in complete media. At 48 h post-treatment, cells were fixed with 70% ethanol, permeabilized with 0. 25% Triton X-100 in PBS, and stained using a propidium iodide/RNase solution (20 μg/ml and 10 μg/ml, respectively). Data were collected on the BD-LSR II flow cytometer (BD Sciences) and analyzed using Flow-Jo (Flow-Jo LLC, Ashland, OR).
Over time, PDAC tumor bearing mice treated with Mito-Met 10 had lower tumor burden when assessed at early, middle, and later time points as visualized by bioluminescent imaging, with smaller tumors at the completion of the study (Fig. 6D ). Serum from these animals was collected, and hepatic and kidney toxicity tested using standard AST, ALT, AP, and BUN assays, respectively. As predicted from cell culture data (Fig. 3 ), neither Met nor Mito-Met 10 elicited toxicity in vivo (Supplemental Table  1 ). Following administration of Mito-Met 10 for two weeks in FC-1242luc orthotopic mice, we detected an increased accumulation of this compound in liver, kidney, spleen, and tumor tissues (Suppl. Fig. 11 ). Collectively, results from the in vivo experiments indicate a potent antitumor activity of Mito-Met 10 , with negligible off-target toxicity.
Acknowledgments Financial support: This work was supported by grants from the  NIH National Cancer Institute  [ U01 CA178960  (to  M. B. Dwinell  and  B. Kalyanaraman ) and  R01 CA152810  (to B. Kalyanaraman)], the  Medical College of Wisconsin Cancer Center  (to  M. B. Dwinell ,  B. Kalyanaraman  and  B. Johnson ) and  Aix-Marseille Université CNRS  (to  M. Hardy  and  O. Ouari ).
Infarct size measurement In regional IR experiments, at the end of reperfusion, the coronary artery was reoccluded. Evans blue dye (2%) was then injected through the cannulated aorta to delineate the area at risk (AR), which remained unstained by the Evans blue solution. The heart was removed and the left ventricle (LV) excised and frozen at -80°C for 15 min, and cut from apex to base into 2 mm-thick transverse slices (6 or 7 per heart). To delineate the IS, the slices were incubated at 37°C with buffered 1% 2,3,5-triphenyltetrazolium chloride (TTC) solution for 10 min, and were then fixed in a buffered 10% formalin solution for 24 h before being photographed. AR and IS were quantified by a blinded observer using a computerized planimetric technique (ImageJ software, NIH, Bethesda, Maryland, USA).
After washing, bound antibody was visualized by use of horseradish peroxidase-conjugated goat anti-rabbit or anti-sheep antibody (1:5000, Cell Signalling, Saint Quentin, Yvelines, France) for 1 hour at room temperature. Loading and quality transfer were evaluated by tubulin staining (1:1000, Santa cruz, La Jolla, CA, USA). Enhanced chemiluminescence was performed with the ECL Western blot detection kit (Amersham, GE Healthcare Europe GmbH, saclay, France) according to the manufacturer's instructions, and blots were exposed to BioRad Camera. Density of protein bands was computerized (ImageJ software, NIH, Bethesda, Maryland, USA). Data are normalized to tubulin (Sigma-Aldrich, Saint Quentin Fallavier, France) and expressed relative to sham group values.
Acknowledgments We wish to thank  Dr C. Arnaud  ( Laboratoire HP2, INSERM, Grenoble, France ),  Pr C. Batandier  ( Laboratoire de Bioénergetique Fondamentale Appliquée, Grenoble, France ) and  Pr R. Clapier-Ventura  ( Laboratoire de Signalisation et Physiopathologie Cardiovasculaire, UMR-S 1180, Paris, France ) for technical assistance and help and  Dr Z. Benlasfar  ( Institut Pasteur de Tunis, Tunisia ) for providing the viper venom. We are grateful to  Pr H. Louzir , head of  Pasteur Institute of Tunis , for support.
The first objective was to track the labeled cells. To this end, a cryogenic probe (Cryoprobe TM , Bruker) was used for high resolution. The second objective was to evaluate the fistula healing by measuring the fistula orifice with the software, Paravision 5. 1, JIVE tool (Bruker), in the three orthogonal planes (Figure  S1 ). This enabled the delimitation of the fistula orifice surface as a region of interest (ROI), for which the size was calculated (cm 2 ).
The density of the microvascular network at the transplantation site and its periphery was also investigated by pCLE after the intravenous administration of FITC-dextran 70 kDa. Mosaicing TM software (Mauna Kea Technologies, France) was employed to enable a real-time display of the draft mosaic gathering the acquired and previous images. A dedicated module, Vessel Detection TM (Mauna Kea Technologies, France), was used to compute the functional capillary density (FCD) and diameter distribution. A diameter of interest (DOI) of 4 µm was chosen to avoid underestimation of small vessels that are the most important in tissue regeneration. The pCLE analysis was carried out at D0 (transplantation time point), D7, and D14.
Statistics The results are presented as means ± standard deviation for continuous variables, and as percentages for categorical variables. GraphPadPrism (Graphpad Software, La Jolla, CA, USA) software was used for statistical analyses. Fischer's exact test was carried out for comparisons between categorical variables and the nonparametric Mann-Whitney test was used for nonpaired continuous variables. Comparisons between more than two groups were performed with the nonparametric Kruskal-Wallis test. Dunn's multiple comparison test difference in rank sum was used for pairwise comparison. A p-value of less than 0. 05 was considered statistically significant.
Acknowledgments This work was supported by  ENCITE , co-funded by the  European Commission  under the 7 th Framework Programme. We sincerely thank  Sophie Camilleri-Broet  ( Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France ) for her assistance in the field of histology;  Josette Legagneux  ( Microsurgery Training and Research Lab, School of Surgery, Paris, France ) for her great advice in the field of microsurgery, and  Nicolas Guegan  ( Institut IMAGINE-INSERM 1163, Paris, France ) for his technical assistance.
Literature search We performed a systematic search on PubMed for articles on breast screening trials. We also searched reference lists in major reviews  [17] [18] [19]  and in publications on breast screening trials we already had. We retrieved all articles reporting original data of these trials. Three of us (PA, MB, MS) read the articles with looking for cancer-specific fatality data reported by categories of size or lymph-node status or stage. For the sake of finding comparable data on screening for other cancers, we performed a similar literature search for colorectal cancer. Fatality could be reported as a proportion of cancer patients who died because of the cancer or as a survival statistics, which is the reverse of fatality. It could be reported as a measure of the risk (e. g. , the hazard rate) to die from a large (more advanced) cancer compared to the risk to die from a small (less advanced) cancer.
Data Extraction One reviewer (B. S. ) will extract characteristics of all the trials including: first author, date of publication, country/ies in which the trial was conducted, sample size, participant characteristics (range and mean age, time since transplant, sex), trial duration, name and type of intervention (eg, surgical, pharmacological, psychosocial, lifestyle), and all outcomes as reported in the trial (including definitions, tools for measurement, thresholds, time points or time frames for measurement, change in level or percentage, scores). Two reviewers (N. E. , A. T. ) will cross check the data extraction.
Data Analysis and Presentation The data will be entered into Microsoft Excel to assist with data management, tabulation, and analysis. Author B. S. will group all similar outcomes into appropriate outcome domains, which will be reviewed and discussed by the SONG-Tx Steering Group (J. R. C. [Chair], K. B. , J. G. , M. A. J. , L. M. , T. P. P. , D. R. , L. R. , A. W. , G. W. ] and SONG Executive Committee (J. C. C. , S. C. , J. G. , T. H. , B. H. , B. M. , P. T. , W. V. B. , D. C. W. , W. C. W. , A. T. ). The outcome domains will be broadly classified as surrogate, clinical, or patient-reported outcomes. We will identify the number of trials that reported each outcome domain. For each outcome domain, we will assess the number of different outcomes (including measures) and the number of trials that assessed each specific outcome and perform statistical analyses using the software package R (version 3.
Purposive sampling to obtain a maximum variation in the demographics, clinical characteristics (patients), and professional experiences and roles (health professionals), and snowballing strategies (where participants can nominate or extend an invitation to other relevant stakeholder members to participate) will be used. Patients/family members will be recruited through participating hospital/university institutions of the SONG Executive, SONG-Tx Steering Group and investigators, patient/consumer organisations, and the SONG Initiative database. Health professionals will be recruited via the collegial networks of the investigators and professional transplantation and nephrology societies.
ACKNOWLEDGMENT The  SONG-Tx initiative  is endorsed by  The Transplantation Society. The authors also want to acknowledge the following organizations for their partnerships and support:  Cochrane Kidney  and Transplant,  Kidney Disease Improving Global Outcomes (KDIGO), PKD International, World Transplant Games Federation, Australasian Kidney Trials Network (AKTN) ,  Christchurch Kidney Society, Kidney Health Australia ,  Transplant Australia , The  Kidney Foundation of Canada ,  British Kidney Patient Association ,  European Kidney Transplant Association (EKITA)  of the  European Society of Transplantation, European Renal Best Practice (ERBP) , and the  UK National Kidney Federation. All SONG Collaborators are listed here: songinitiative. org/who-we-are/partnersand-supporters/.
CMV QNAT was performed once a week for the first 3 mo, once a month between months 3 and 6, and then every 2 months up to 1 year and if CMV disease was suspected clinically. During the virological monitoring of CMV disease, the assay was performed once a week until two consecutive negative CMV DNAemia QNATs occurred. Antiviral drug resistance was suspected when persistent viral replication was observed after >2 weeks of appropriate antiviral therapy and was confirmed by fulllength sequencing of the UL97 and UL54 genes  (25) , performed at the French National Cytomegalovirus Reference Center (Limoges, France). Sequences were compared with the AD169 reference sequence using the Gene Librarian 3. 2 software (Visible Genetics Inc. , Siemens, France)  (26, 27).
Flow cytometry analysis and monitoring of Vd2 neg cd T cells Blood samples were analyzed at the Bordeaux University Hospital immunology laboratory by flow cytometry using a FC500 flow cytometer from Beckman Coulter. All blood samples were withdrawn on EDTA anticoagulant in Vacutainer 5-mL tubes (BD Biosciences, Mountain View, CA) and kept at room temperature until processed. Following the manufacturer's recommendations, labeling was carried out on whole blood and red blood cells lysed at room temperature with a Versalyse (Beckman Coulter France, Villepinte, France) lysing solution added to Iotest fixative solution (Beckman Coulter, Macon, France). Events were acquired with the dedicated CXP-1 software. Vd2 neg cd T cells were detected with anti-Vd2 and anti-PAN-d, purchased from Beckman Coulter France.
The GWAS meta-analysis results included three associations in novel loci (rs17603856 (6p23), rs1887428 (9p24) and rs669763 (16q13)) with genome-wide levels of significance (P < 5 × 10 -8 ; Fig. 1b ). In addition, the major histocompatibility complex (MHC) and, to a lesser extent, the IRF5 locus on chromosome 7 showed significant transancestral heterogeneity (Fig. 1b ). We then carried out a two-stage replication study incorporating rs17603856, rs1887428 and rs669763. We scanned the 1KG imputed data for association at loci independent of those previously published and excluding the MHC. We successfully genotyped a total of 66 SNPs at 56 loci (SNP selection is described in the Online Methods) in an additional 3,043 cases and 5,074 controls of Chinese ancestry recruited from Anhui Province. Eighteen of these SNPs (at 17 independent loci) showed association in this replication study, passing a false discovery rate (FDR) of 0.
01. These included rs17603856 and rs1887428 but not rs669763, which failed quality control. We then genotyped these 18 SNPs in a European replication cohort comprising 1,478 cases and 6,925 controls3. Data from an additional European-American GWAS (1,165 independent cases and 2,107 controls) were also included in this final analysis15 (Supplementary Table  2a ). Of the 18 candidate SNPs, 11 showed a standard genome-wide level of significance (P < 5 × 10 -8 ) in the combined meta-analysis  (11, 381  cases and 24,463 controls) of all three main GWASs and the three replication studies (Table  1 , Supplementary Fig. 1 ). The strongest association signal after this meta-analysis was that for rs1887428 (9p24; P = 2. 19 × 10 -17 ). Other statistically significant associations were found at rs34889541 (1q31.
Statistical analysis Association testing-After imputation, we analyzed each GWAS data set for association (SNPTEST36), fitting an additive model. We used the inverse variance method for metaanalysis, combining data from the three studies for SNPs with an imputation INFO score of >0. 7 in all three studies. Testing for heterogeneity. We tested for heterogeneity between the association signals in the Chinese and European data using Cochran's Q statistic (1 degree of freedom in this case). The P values on the -log 10 scale are plotted in Figure  1b. Q-Q plots (one per chromosome) for the heterogeneity P values can be seen in Supplementary Figure  9a , and Bland-Altman plots for differences in genetic effect (log odds ratio) estimates are in Supplementary Figure  9b. Assessment of shared association between ancestries-To assess the extent to which genetic association with SLE was shared between the Chinese and European populations, we compared association results in the European GWAS3 with a meta-analysis of both Chinese GWASs, for SNPs published as associated in European3 and/or Chinese studies4,6-9.
Although this did not identify any additional shared loci (Supplementary Table  1b ), there was suggestive evidence for two loci (P < 0. 05 after multiple testing adjustment within loci but not after adjusting across loci). Consistency of association between ancestries-We tested the hypothesis that the genome-wide association signals were consistent between the two populations. Post-1KG imputed association data were used for SNPs with INFO > 0. 7. These genome-wide association signals were separated into 1-Mb regions (moving 1-Mb windows across the genome, 2,698 in total). We removed the extended MHC with a conservative buffer zone (chr. 6, from 20 Mb to 40 Mb), leaving 2,678 regions. We also removed regions that had an excessively (more than 2 s. d. from the average) low (N < 1,000) or high (N > 3,000) density of SNPs.
This removed only 10% of the regions, leaving 2,338 regions. The lowest P value within each window was taken as the strength of association for that particular window. Each P value within each region was adjusted for multiple testing using a Bonferroni adjustment, to avoid bias in ranking agreement owing to the lowest P value being correlated with the number of statistical tests. The 1-Mb regions within each population's data were then ranked according to the P value (lowest P value having rank 1). We tested agreement in ranking using Kendall's τ statistic. Supplementary Figure  7c  shows heat maps of the ranks for all 2,338 regions, the top 250 regions and the top 50 regions. The order in the heat maps was determined by the sum of the ranks. For comparison, we also included a simulated ranked data set; we permuted the numbers 1-2,338 in two separate data sets and produced a heat map ordered by the sum of the ranks.
Testing for independent effects within loci-We tested for independent effects of the two SNPs (rs17321999 and rs7579944) within the 2p23. 1 locus by fitting a multiple regression model with both SNPs as explanatory variables (results for each SNP in this analysis are conditional on the other SNP as a covariate). We checked LD between the two SNPs in all data sets. We combined the conditional results in meta-analysis in the same way as in the single-marker analysis. Selection of SNPs for replication study-We used a number of criteria to select SNPs for replication in the Chinese samples. We chose only SNPs that were not within a 1-Mb window of loci that had previously been published as associated with SLE. We selected SNPs that had P value significance levels at meta-analysis of <10 -4. Three SNPs in loci not previously reported as associated with SLE had a genome-wide level of significance (P < 5 × 10 -8 ) after meta-analysis.
SNPs spanning a 1-Mb window were considered as one region, and we selected only independent SNPs within this region, using LD as a measure of independence. We carried out a gene-based test on the meta-analyzed data, using only SNPs with INFO scores > 0. 9, with the software KGG39-41. One SNP from each of the loci that passed a gene-based test at the level of P < 10 -5 was chosen; some of these had already been selected as having P < 10 -4 in the meta-analysis as single markers. In total, 105 SNPs were selected for replication in the Chinese replication cohort. Of these, 66 passed QC, and 18 SNPs with FDR < 1% were taken forward to the European replication.
Genotyping of replication data Genotyping of 130 SNPs was carried out for the 3,614 cases and 5,924 controls forming the Chinese replication set, using the Sequenom platform. This set of 130 SNPs included 105 SNPs in loci not previously reported as associated with SLE and 25 SNPs in loci that had previously been published as associated with SLE. The 105 potential new SLE SNPs included, in some cases, multiple SNPs in the same loci where we had some evidence of independence. We carried out several QC steps: we removed SNPs with >10% missing data (25 SNPs), and then subjects with >5% missing data. Two SNPs were monomorphic. Of the remaining 103 SNPs, 77 were in regions of the genome with potential new SLE associations. We removed 13 SNPs after we checked the genotyping allele intensity plots closely for clustering quality and tested for Hardy-Weinberg equilibrium (HWE).