dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at  CERN  and at other  CMS institutes  for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing centres and personnel of the Worldwide LHC Computing Grid for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC and the CMS detector provided by the following funding agencies: the  Austrian Federal Ministry of Science, Research and Economy  and the  Austrian Science Fund ; the  Belgian Fonds de la Recherche Scientifique , and  Fonds voor Wetenschappelijk Onderzoek ; the  Brazilian Funding Agencies (CNPq, CAPES ,  FAPERJ , and  FAPESP) ; the  Bulgarian Ministry of Education and Science ; CERN; the  Chinese Academy of Sciences, Ministry of Science and Technology , and  National Natural Science Foundation of China ; the  Colombian Funding Agency (COLCIENCIAS) ; the  Croatian Ministry of Science, Education and Sport , and the  Croatian Science Foundation ; the  Research Promotion Foundation , Cyprus; the  Secretariat for Higher Education, Science, Technology and Innovation, Ecuador ; the  Ministry of Education and Research, Estonian Research Council  via  IUT23-4  and  IUT23-6  and  European Regional Development Fund , Estonia; the  Academy of Finland ,  Finnish Ministry of Education and Culture , and  Helsinki Institute of Physics ; the  Institut National de Physique Nucléaire et de Physique des Particules / CNRS , and  Commissariat à l' Énergie Atomique et aux Énergies Alternatives / CEA , France; the Bundes-.
After three washes, membranes were blocked with secondary antibody anti-rabbit ads-HRP (1:5000, #4050-05, Southern Biotech, Birmingham, AL, USA). Membranes were incubated in ECL Clarity Western Substrate (Bio-Rad Laboratories) and detection was performed on a ChemiDoc™ Touch Imaging System (Bio-Rad Laboratories) coupled with Image Lab™ Touch Software; quantification was expressed as the ratio of proteins over GAPDH densities.
Real-time PCR qPCR was performed in triplicate at 25 µL final reaction volume (5 μL of IP or input, 1X de TaqMan ® Universal PCR Master Mix (Applied Biosystems), 400 nM for each forward and reverse primers (Sigma-Aldrich), 250 nM of probe (Applied Biosystems) (Table  2 ) and 4. 25 μL of water) on a 7900 HT Fast Real Time PCR System (Applied Biosystems). The recovery level of proteins was disclosed by the rate of IP relative to Input. The efficiency of chromatin immunoprecipitation of a particular genomic locus can be calculated from qPCR data and reported as a percentage of starting material: %(ChIP/Total Input) = 2^[(Ct(x%input) -log(x%)/log2) -Ct(ChIP)] × 100%. Ct (input) and Ct (ChIP) are threshold values obtained from the exponential phase of qPCR for the immunoprecipitated DNA sample and input sample respectively.
Flow cytometry Fluorescence (FL) was quantified on a SORP FACSAria2 (BD Biosciences) as previously described  [14, 16]. Data were processed with FACSDiva 6. 3 software (BD Biosciences). Doublets were excluded by FSC-W x FSC-H and SSC-W x SSC-H analysis. Charts display the median of fluorescence intensity (mfi) relative to control. Single stained channels were used for compensation and fluorophore minus one (FMO) controls were used for gating. 20,000 events were acquired per sample. Cells from ascites fluids were stained with EpCam APC conjugated (BD Biosciences) and the fluorescence was acquired with 647 nm red laser and 670/14 nm emission. MSC were defined as Lin -CD45 -CD90 + CD73 + CD105 + CD29 +. The cell suspension was stained with mouse anti-human CD45 antibody (BD biosciences, #339192, clone 2D1) coupled with Amcyan, anti-mouse lineage cocktail 1 (Lin, BD biosciences, #340546, CD3, CD14, CD16, CD19, CD20, CD56) coupled with FITC, mouse anti-human CD105 (biolegend, #323212, clone 43A3) coupled with AF647, mouse anti-human CD73 (BD biosciences, #550257, clone AD2) coupled with PE, mouse anti-human CD29 (biolegend, #323212, clone TS2/16) coupled with APC-Cy7, mouse anti-human CD90 (BD biosciences, #550402, clone 5E10) coupled with AF700.
Western blot analysis Western blot were carried out as previously described  [14]. Immunostaining was carried out using a goat monoclonal antibody against Phospho PYK2 #3291, PYK2 #3292, IL-6 #2153, actin #3200 (1/1000, Cell signaling) and a secondary polyclonal mouse anti-goat antibody HRP conjugated (1/ 2000, cell signaling). Blots were developed using HRP and chemiluminescent peroxidase substrate (#CPS1120, Sigma). Data were collected using Geliance CCD camera (Perkin Elmer), and analyzed using ImageJ software (NIH).
Cytokine array All cells were starved for 24 h prior the cytokine Array experiment. 200 μg of protein was loaded on RayBio® Human Cytokine Antibody Array G Series 1000 (Raybiotec, Norcross, GA) according to manufacturer's instructions. Arrays were revealed using HorseRadish Peroxidase (HRP) and SuperSignal West Pico Chemiluminescent Substrate (Thermo-Scientific, Dubai, Emirates). Data were collected using Geliance CCD camera (Perkin Elmer, MA), and extracted using ImageJ software (NIH). Briefly, the pictures of the arrays were inverted and background subtracted. We then defined the area for signal capture for all spots as 110-120 μm diameter, using the same area for every spot. We defined our signal as the median pixel density value. For the comparison, the independent arrays values were normalized on their positive control intensity value.
Statistical analysis All quantitative data were expressed as mean ± standard error of the mean (SEM). Statistical analysis was performed with SigmaPlot 11 (Systat Software Inc. , Chicago, IL). A Shapiro-Wilk normality test, with a p = 0. 05 rejection value, was used to test normal distribution of data prior further analysis. All pairwise multiple comparisons were performed by one way ANOVA followed by Holm-Sidak posthoc tests for data with normal distribution or by Kruskal-Wallis analysis of variance on ranks followed by Tukey posthoc tests, in case of failed normality test. Paired comparisons were performed by Student's t-tests or by Mann-Whitney rank sum tests in case of unequal variance or failed normality test. All experiments were performed in triplicates. We used Wilcoxon test to compare mean peritoneal carcinosis index between the different treatment regimen groups of mice.
Follow-up visits were scheduled at 6 wk, 6 mo, and 12 mo after surgery (Supplementary material, Follow-up and assessment of complications). Eligible participants were randomly assigned at a 1:1 ratio to LS or TVM. The randomization process was performed centrally online using a password-protected database, with balanced blocks of four patients, stratified by center and by sexual activity (yes/no). The random number list was generated before the beginning of the study by an independent statistician researcher using computer-generated random numbers (SAS Proc Plan). Randomization was performed by the investigator after obtaining informed consent from the patient, and after clinical assessment and questionnaires. Allocation was revealed only when baseline data for a patient were provided. Patients were informed of their treatment assignment a few days before surgery.
The primary outcome was the rate of complications of grade II or higher in the modified Clavien-Dindo (mCD) classification  [10]. Three independent assessors, blinded to the surgical arm, were appointed to grade the complications. Each complication was extracted from the database and revised to remove all characteristics related to the approach, so that the assessors were completely blinded to the surgical arm. Before the gradation began, a consensus on grading based on the literature  [11] [12] [13]  was provided and achieved with the experts in order to give assistance for cases difficult to grade with the mCD, and to minimize the interobserver disagreement. After training on 20 cases with consensus feedback, the assessors were sent the complication reports in random order. Each assessor has to decide first whether a given case of complication was attributable to the study and then to grade it according to the mCD.
All statistical tests were two sided. All analyses included the patients' full data set, except for those who withdrew their consent. In cases of missing data or incomplete follow-up, analyses were performed after multiple imputation of missing data using the PROC MI procedure. Analyses were performed using SPSS version 22 (SPSS Inc. , Chicago, IL, USA). This study has been conducted in accordance with the original protocol  [19]  after approval by the Institutional Review Board.
Comité de Protection des Personnes Nord-Ouest IV, 2011-A0128239). The trial was registered in the ClinicalTrials. gov registry (NCT01637441) and at the French Safety Agency (AFSSAPS B111368-30). The French Ministry of Health (PHRC 2011/1921) funded the study, but had no role in the study design, collection, analysis, and interpretation of data, writing of the report, and decision to submit the paper for publication. The study had no support or involvement by any manufacturer of mesh.
Acknowledgments: We thank all women included in the present study. We thank all the participants: Surgeons who participated in the study (and those not listed as the authors):  Pierre Collinet ,  Geraldine Giraudet ,  Hervé Fernandez ,  Magali Lesavre ,  Perrine Capmas ,  Guillaume Legendre ,  André Nazac ,  Erika Faivre ,  Caroline Trichot ,  Géraldine Demoulin ,  Etienne Vincens ,  Christine Dehghani ,  Catherine Frey ,  Amirata Kane ,  Pierre Gadonneix ,  Jean-Sebastien Aucouturier ,  Yannick Thirouard ,  Brigitte Fatton ,  Laurent Wagner ,  Cédric Nadeau ,  Olivier Garbin ,  Véronique Thoma ,  Emmanuelle Baulon Thaveau ,  Christian Saussine ,  Didier Tardif. Promotion and monitoring of the study:  Edouard Millois , from the  CHRU of Lille, France. Independent experts who assessed the complications:  Professor Michelle Nisolle  ( CHR Citadelle, Liège, Belgique ),  Professor Jan Deprest  ( Universitaire Ziekenhuizen Leuven Campus, Gasthuisberg, Leuven, Belgique ), and  Professor Patrice Mathevet  ( CHUV, Lausanne, Suisse).
( Comité de Protection des Personnes Nord-Ouest IV, 2011-A0128239). The trial was registered in the ClinicalTrials. gov registry (NCT01637441) and at the French Safety Agency (AFSSAPS B111368-30). The French Ministry of Health (PHRC 2011/1921) funded the study, but had no role in the study design, collection, analysis, and interpretation of data, writing of the report, and decision to submit the paper for publication. The study had no support or involvement by any manufacturer of mesh.
S1C  and S1D ). Total leukocyte counts also tended to diminish following MG1-MAGEA3 treatment, being most apparent in Ad-MAGEA3-pre-treated animals, independently of MG1-MAGEA3 dose (Fig. S1E  and S1F ). Transient and clinically silent grade 1/2 elevations of ALT were documented in both groups (data not shown). One primate had a chronic high-grade elevation of ALT that pre-dated vaccination, this animal was diagnosed histologically with intrahepatic hemosiderosis. Overall, MG1-MAGEA3 was well tolerated by primates with only low-grade adverse events ascribed to animals receiving Ad-MAGEA3:MG1-MAGEA3.
MG1-MAGEA3 bio-distribution and shedding Multiple tissues from macaques were analyzed for viral biodistribution (Table  S2 ). All animals had Maraba RNA viral genomes detectable in the blood by RTqPCR (data not shown). Among tissue subtypes, immune-related organs (spleen and lymph nodes) were the most frequently positive for MG1-MAGEA3 genomes (Fig. S2A ). No detectable viral plaques were identified in any of the tissues positive for MG1-MAGEA3 by RTqPCR, indicating that the genomes identified were non-replicating MG1-MAGEA3. No Ad-MAGEA3 genomes were detected by qPCR in any tissue. All fecal samples tested for MG1-MAGEA3 by RTqPCR were negative. MG1-MAGEA3 genomes were detected in the urine of 3 animals treated with high-dose MG1-MAGEA3, without replicating virus being present (data not shown).
Ad-MAGEA3 priming efficacy was evaluated in the 20 macaques enrolled in the five prime-boost cohorts: AM6w-lo, AM6w-hi, AM2w-lo, AM2w-hi, AM4w-hi (Figure  1A ). hMAGE-A3-specific T-cell populations were quantified before and 14 days after intramuscular injection of Ad-MAGEA3. At day 14, mean Ad-primed response was 4. 46 ± 1. 49 IFNγ + CD8 + T-cells/µl blood and accounted for more than 0. 5% (0. 62 ± 1. 02%) of all total circulating CD8 + T-cells (Figure  2C, D ). Additionally, the prime response was evaluated at day 28 post-Ad-MAGEA3 (AM4w-hi cohort (n = 4)) and at day 42 (AM6w-lo and AM6w-hi cohorts (n = 8)). At these later time-points, the reactive CD8 + T-cell population had expanded in only 25% of the primates assessed (n = 3/12, data not shown). Overall, the mean response remained stable over a month after Ad-MAGEA3 (Figure  2C, D ).
MG1-MAGEA3 boosts hMAGE-A3 specific CD4 + T-cells Specific hMAGE-A3 CD4 + T-cell immunity was also evaluated. MG1-MAGEA3 alone failed to prime detectable CD4 + responses (data not shown). Mean priming of the CD4 + T-lymphocyte compartment following Ad-MAGEA3 injection was of lower magnitude than the CD8 + subset (Figure  3A, B ). Of the 20 immunized macaques, 40% (n = 8) displayed reactivity above the pre-immune baseline with a maximum of 0. 29 IFNγ + CD4 + T-cells/µl blood observed in AM6w-lo 4 (Fig. S5A ). All 20 macaques that received the Ad-MAGEA3 prime were boosted with MG1-MAGEA3 either at a 6-week interval in the AM6w-lo and AM6w-hi cohorts, 4-week interval in the AM4w-hi cohort, or 2-week interval in the AM2w-lo and AM2w-hi cohorts (Figure  1A ). MAGE-A3-specific T-cell populations were quantified at day 5 (n = 20), 13 (n = 20) or 84 (n = 6) after intravenous MG1-MAGEA3.
Factors impacting the magnitude and quality of vaccineinduced cellular immunity Additional analyses were performed to interrogate the effects of experimental variables and individual characteristics of macaques on the induced hMAGE-A3 cellular immunity. Variations in gender, age, interval between Ad-MAGEA3 and MG1-MAGEA3 administration and the dose of MG1 did not affect vaccine immunogenicity (data not shown). However, predominant reactivity against MHC-I-restricted epitope(s) located in the N-terminal region covered by the pool of peptides 11-20 was associated with weaker CD8 + T-cell boost responses (macaques AM6w-lo2, AM6w-hi1 and AM6w-hi2, Figure  5A ). Thus, individual variables affecting antigen presentation and/or recognition were implicated as determinants for the magnitude of cellular immunity.
Ad-MAGEA3:MG1-MAGEA3 induces auto-reactive T-cells To further appraise the potential clinical relevance of oncolytic vaccination, the ability to invoke populations of auto-reactive Tcells was tested. For this purpose, T-cell epitope mapping of the hMAGE-A3 was performed. Blood from 16 out of the 20 macaques that received Ad-MAGEA3 plus MG1-MAGEA3 was collected (the four weakest responders were excluded). Circulating simian T-cells were re-stimulated for 24 hours with each individual peptide of the hMAGE-A3 peptide library. Immunogenicity and relative immune dominance of every peptide was characterized by ELISpot (Figure  6A ). Subsequently, peptides with sequence homology between human and macaque were identified by blasting the H. sapiens MAGE-A3 reference sequence (accession number: P43357) against the NCBI protein database and allowed identification of three M.
fascicularis MAGE-A3 sequences (accession numbers: XP_005594921, XP_015299818, XP_005594918). Sequence alignment revealed that the 314 amino acids of the human and cynomolgus MAGE-A3 were 89% identical (Fig. S3B ). Highly conserved regions were encompassed within 17 of the 87 peptides. Among them, eight peptides shared sequence identity (#31-36, 42, 61) while the other nine differed by only one amino acid located at the N-or C-terminal extremity (#6, 26, 27, 30, 53, 60, 73, 77, 78; Fig. S3A ). Fourteen of 16 macaques (88%) that received Ad-MAGEA3:MG1-MAGEA3 demonstrated T-cell reactivity against highly conserved MAGE-A3 peptides (Figure  6B ). With the exception of peptide #32, cellular immunogenicity was observed at least once against each of the highly conserved peptides (Figure  6B ). T-cell responses against conserved peptides were mostly subdominant compared to non-conserved peptides.
Discussion Due to their multi-faceted mechanisms of action and ability to engage the endogenous immune system, various oncolytic viruses (OVs) are undergoing clinical assessment. 36 Two phase I/II clinical trials using the MAGE-A3 oncolytic vaccination platform are underway. The first utilizes the oncolytic Maraba MG1-MAGEA3 vaccine, either alone or following Ad-MAGEA3, for the treatment of patients with advanced MAGE-A3-positive solid malignancies (NCT02285816). The second is evaluating the treatment of MAGE-A3-positive nonsmall cell lung cancer (NSCLC) in combination with pembrolizumab (NCT02879760). The comprehensive safety profile and potent immunogenic properties documented herein were key facilitators to enable the launch of these first-inman studies. Following systemic administration of 1 × 10 10 PFU (low dose) or 1 × 10 11 PFU (high dose) MG1-MAGEA3, only mild and transient constitutional adverse events were recorded.
48 MG1 genomes were found predominantly in secondary lymphoid organs. This distribution supports the ability of MG1-MAGEA3 to directly boost T CM resulting in massive expansion of effector T-cells as previously elucidated in mice. 31 MG1-MAGEA3 was capable of inducing very large and specific anti-MAGE-A3 immunity comprising up to 13. 47% of all circulating CD8 + T cells in primates. Some limitations were inherent in this study. In order to avoid loss of cellular viability secondary to freeze/ thawing, flow cytometry was performed on fresh samples hence there may be some variability between differing runs. The same personnel performed sample processing and data acquisition following identical protocols to minimize operator and procedural variation. As all animals were tumor free, no detectable viral replication occurred.
] [25]  Toxicity has been associated with acute, massive cytokine release in some immunotherapeutics, such as CAR T-cells. 49 ytokines were not monitored in this study as their importance in a tumor-free animal is questionable. In most primates, cellular immunity rapidly contracted after boosting. Whether such kinetics will be reflected in the case of ongoing antigenic stimulation by the tumor is unknown. Finally, when using healthy hosts, studying the effect of oncolytic vaccination on the TME was not possible and, although we clearly demonstrate the induction of circulating immunity, how the oncolytic Maraba MG1 virus and effector immune populations will interact within the TME of spontaneous tumors remains to be determined. Data gathered during our clinical trials will address these areas of intrigue.
Leukocytes were stained with the above listed surface antibodies for 25 minutes at 4°C in FACS buffer (PBS containing 0. 5% bovine serum albumin). Cells were permeabilized and fixed with Cytofix/Cytoperm (BD Biosciences, ON, Canada) for 20 minutes at 4°C in FACS buffer and finally stained for intracellular cytokines for 25 minutes at 4°C in FACS buffer. Data were acquired using a FACSCanto cytometer with FACSDiva software (BD Biosciences, ON, Canada) and analyzed with FlowJo Mac software (Treestar, OR, USA). Absolute counts of reactive lymphocytes were obtained taking into account the following parameters: i) the proportion of the whole blood cell suspension processed and stained; typically 200 µl of whole blood for each peptide re-stimulation condition out of the 2 ml drawn per macaque (normalization factor #1) and ii) the proportion of the stained cell suspension ran through the flow cytometer; typically 300 out of 400 µl of the stained lymphocyte suspension (normalization factor #2).
Bioinformatics M. fascicularis MAGE-A3 sequences were identified in the NCBI protein database using the BLASTP program (blast. ncbi. nlm. nih. gov/) and the H. sapiens MAGE-A3 reference sequence (NCBI accession number: P43357) as protein query. Sequence alignment was performed using Clustal Omega (www. ebi. ac. uk/ Tools/msa/clustalo/).
Statistical analyses Linear mixed effect models were fitted to analyze weekly weight variation from baseline between experimental arms (MG1-MAGEA3 alone versus Ad-MAGEA3 + MG1-MAGEA3) and dose groups (low versus high dose) considering the time points as fixed effects. Statistical analyses were performed using SAS version 9. 4 (SAS Institute Inc. , NC, USA). For vaccine immunogenicity, GraphPad Prism version 6 for Windows (GraphPad Software, San Diego, CA) was used for data graphing and the R software for statistical analysis. 51 Immune data are displayed as histograms or scatter plots displaying the mean value ± standard deviation (SD). For testing data normality, we applied the Shapiro-Wilk test and considered that data distribution was not normal when p-value < 0. 05. For comparing two conditions, we applied the Wilcoxon test when data distribution was not normal while the Welch t-test was used for normally distributed data sets.
Acknowledgments We would like to express many thanks to  U. Sankar ,  A. del Rocio Ortega Rolando  and  M. F. C. Medina (Robert E. Fitzhenry Vector Laboratory ,  McMaster Immunology Research Centre, Hamilton, ON, Canada ) for the production of both Ad-MAGEA3 and  MG1-MAGEA3  viruses. Our appreciation also goes to  S. Avery  and  M. D'Souza  ( UHN Animal Resource Centre, Toronto, ON, Canada ) for assisting with animal housing and experiments. Finally, we want to express our gratitude to  A. C. Smith ,  A. Laporte ,  J. Hamill ,  M. Becker  and  X. Gao  ( Ottawa Health Research Institute, Ottawa, ON, Canada ) for their technical assistance in screening tissues for Maraba virus detection.
Study design The present study is a monocentric retrospective hospital-based cohort which included adult kidney graft recipients evaluated between June 2007 and January 2016 in the department of renal Physiology (Tenon Hospital, Paris, France) three months after transplantation. Among the 406 recipients recorded, three months CF-PWV data were unavailable for 186 patients. Thus 220 patients were included in the study (Fig  1 ). Follow up was completed for all patients. The end of follow up was censored on January 1 st , 2017. All participants signed a written informed consent and data collection was approved by the CNIL according to French legislation (n˚2065902v0).
Data and measurements All kidney recipients received a standard immunosuppressive regimen including an induction therapy (methylprednisolone associated with basiliximab or Anti-thymocyte globulin) followed by a tritherapy associating CNI (tacrolimus or ciclosporin), corticosteroids (tapered to 5 mg/day after one month) and Mycophenolate mofetil. Clinical and laboratory data at 3 (M3) and 12 months (M12) after kidney transplantation at the physiology department were retrospectively collected. They included demographics, medical history, primary renal disease diagnosis, height and weight, resting blood pressure (BP), and medications. Elevated blood pressure was defined by a systolic BP !140 mm Hg and/or diastolic BP !90 mm Hg and/or antihypertensive drugs intake. At each visits, GFR was measured by 51Cr-EDTA renal clearance as described previously  [20].