dataesr/scientific-paragraphs-categorization huggingface dataset:
Protocol Approval and Patient Consent In 2011, the Institutional Review Board and the Ethical Committee of St. Louis Hospital approved the prospective follow-up of a cohort after immune profiling in order to document their outcome and a potential benefit (ref. 2011-A00994-37). All women provided written informed consent at the time of the endometrial collection, allowing to be contacted directly or through their physicians to collect the outcome at the first subsequent transfer following the uterine immune profiling. In 2014, we launched a randomized control study, the PRECONCEPTIO trial (NCT02262117). The PRECONCEPTIO trial evaluates the interest of the Pre-conceptional Endometrial Immune Profiling to Increase Birth Rates (NCT02262117) in good prognosis IVF patients. This randomized control trial (RCT) began to include patients in August 2016 and plan to randomize 400 dysregulated patients.
Patients The following information were for the patients undergoing endometrial biopsy: the age, the etiology of the infertility, the number of previous oocytes collections, the cumulated total number of embryos replaced, and the next treatment plan (fresh IVF with own eggs, Frozen embryo transfer FET, IVF with donor eggs IVF-OD, monitored natural cycles). One thousand seven hundred and thirty-eight patients were included in this prospective cohort study. According to the data collected, patients were divided in different categories according to the clinical context (IVF/ICSI; oocyte donation, recurrent miscarriages) and to the number of attempts and the number of embryos previously replaced (beginning their course in IVF or IVF-OD vs. history of RIF with their own oocytes or with OD) (Table  1 ): -1,145 patients had a history of RIF, defined as the failure to get pregnant despite the cumulated transfers of at least 6 embryos over at least two oocytes collections for patients younger than 43 years old.
However, if the embryo does not have the capacity to control the local immune dysregulations, personalized treatment may be important to promote an effective initial dialogue. The absence of variation when considering the maternal age also suggests that the oocyte's quality and the endometrial immune local balance appear to be independent. In the subgroups where the oocyte's quality was controlled (Good prognosis IVF or OD), the highest pregnancy rates were observed in non-dysregulated patients. For dysregulated patients, the key missing data is what would have been their pregnancy rate if no personalization had been applied. In 2016, we launched a randomized control trial in good prognosis IVF patients to cover this question. Five hundred patients are to be enrolled. If a dysregulation is diagnosed, patients are randomized for either a conventional IVF cycle or a personalized IVF cycle.
ACKNOWLEDGMENTS We first thank the patients who agreed the retrospective collection of their pregnancy outcome. We also want to thank the physicians who agreed to participate to the innovative Procedure:  F. Alexandre ,  F. X. Aubriot ,  J. P. Ayel ,  G. Baroche ,  B. Bstandig ,  I. Cedrin ,  C. Cornelie ,  D. Cornet ,  A. Delvigne ,  S. Demelenne ,  E. Descat ,  C. Denoual-Ziad ,  V. Divry ,  S. Douard ,  R. Elbaze ,  F. Farges ,  A. Godefroy ,  J. Greindl ,  F. Herve ,  L. Larue ,  X. Lechat ,  O. Mialon ,  C. Nathan ,  P. Oger ,  M. Pasquier ,  A. Schumacker ,  A. C. Roubach ,  G. Rege ,  C. Vasseur , and  S. Verge. We particularly thank physicians of the reproductive unit of the hospital  Les Bluets (Paris)  for their enthusiasm and support. Finally, we also want to thank  Joel and Jonathan Hamon  who adapted the secured and online medical file dedicated to infertility (Medifirst SAS) to our innovation implementing new data and the informatics support to extract relevant data and generate the reports.
2 ± 1. 1 nm (N = 60)), for CHMP4B/CHMP2A/ CHMP3 samples (d = 4. 4 ± 1. 2 nm (N = 66)) and for CHMP4B only (d = 4. 4 ± 0. 8 nm (N = 31)) (Fig. 3m ). In addition, striations perpendicular to the long axis of the tubes are also present (Fig. 3j , arrows). To further quantify this observation, we have performed 2D classification out of 350 sub-portions of tubes for the CHMP4B/CHMP2B sample (Fig. 3n , top). The 10 resulting classes and the resulting Fourier transformation show unambiguous evidence for periodical structures both along the axis of the tubes (red line) and perpendicular to the tube (blue line, 20% of the dataset) (Supplementary Fig. 8F ). In Fourier space, all classes generated peak densities along the direction related to the tube axis (red) (Fig. 3n , bottom and Supplementary Fig.
9A ), we observed that 14 filaments decorate the tubular structure in a periodic and regular pattern, independent of the curvature (Supplementary Fig. 9A , Supplementary Movies 6 and 7). The reconstruction was obtained at a resolution of 26. 1 Å (See FSC curve in Supplementary Fig. 9B ). The third population consists of paired filaments that were found in only 3% of the dataset (Fig. 4b ) and its final average was determined at a resolution of 26. 1 Å (see FSC, Supplementary Fig. 9B ) (Supplementary Movie 8), Interestingly, multireference analysis (MRA), resulted in different classes grouped according to their distribution along the pipe (Supplementary Fig. 9C : class 1 and class 2). Class 1 corresponds to negatively curved portion of tubes (inner side), where filaments are scarce (Supplementary Fig.
9D ). Class 2 corresponds to filaments bound to the outer side of tubes (positive curvature) with a higher density, suggesting that paired ESCRT filaments have a higher affinity for positively curved membranes. A similar asymmetric distribution has been described in a recent report on yeast ESCRTs  53. The fourth population, comprising the remaining 30% of the dataset, is composed of filaments bridged by protein connections perpendicular to the main axis of the tubes (see Fig. 4c , arrows) (Supplementary Movie 9). Its final average was determined at 28. 3 Å resolution. This set of bridging proteins is most likely related to the striations perpendicular to the main axis of the lipid tubes visualized in Fig. 3j , highlighted by diffraction spots perpendicular to the main axis of lipid tubes (Fig.
26 Å. The consecutive images were aligned using the IMOD software suite  63. Back projection was performed using IMOD and SIRT reconstruction was carried out using Tomo3d. The segmentation was performed manually using IMOD. The dataset used for sub-tomogram averaging consisted of 28 tilt-series collected at the Electron Microscopy Core Facility of the European Molecular Biology Laboratory (EMBL) in Heidelberg. Image acquisition was performed on a Titan Krios microscope (FEI) operated at 300 kV using a Quantum post-column energy filter and a Gatan K2 Summit direct detector controlled by SerialEM  64. Tiltseries were collected using the dose-symmetric scheme (Hagen et al. 2017) in the range of ±60°and a 3°angular increment and a defocus range between -1. 5 and -4. 25 μm. Tilt images consisted of 13 super-resolution frames with a total dose per tilt-series of 140 e -Å -2.
For experiments involving encapsulation and fusion, the tube was pulled from the PI(4,5)P2-containing GUV prior to fusion, using a streptavidin-coated bead hold by a third micromanipulator. Fusion was then performed between the GUV pair, keeping the membrane tube in place. The values of tube diameter (in nm) were deduced from the lipid fluorescence intensities the tube in comparison with the fluorescence in the GUV, after calibration: High-speed AFM. All HS-AFM data were taken in amplitude modulation mode using a sample scanning HS-AFM [Research Institute of Biomolecule Metrology (RIBM), Japan]. Short cantilevers (USC-F1. 2-k0. 15, NanoWorld, Switzerland) with spring constant of 0. 15 N/m, resonance frequency around 0. 6 MHz, and a quality factor of ∼2 in buffer were used. The cantilever-free amplitude is 1 nm (3 nm for imaging liposomes), and the set-point amplitude for the cantilever oscillation was set around 0.
Acknowledgements The authors thank  Daniel Levy  for support and insightful discussions,  Michael Henderson  for carefully reading the manuscript. We thank  Eric Nicolau  for his drawing skills. This work was initiated with a grant from  FINOVI  (W. W. , P. B. ) and was supported by the  ANR  ( ANR-14-CE09-0003-01 ) (W. W. , P. B. ), by the  Institut Curie  and the  Centre National de la Recherche Scientifique (CNRS). W. W. acknowledges the  Institute Universitaire de France (IUF)  and the platforms of the Grenoble Instruct-ERIC center (ISBG;  UMS 3518 CNRS-CEA-UGA-EMBL ) within the  Grenoble Partnership for Structural Biology  (PSB). Platform access was supported by  FRISBI  ( ANR-10-INBS-05-02 ) and GRAL, a project of the  University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS  ( ANR-17-EURE-0003 ).
For cryo-electron microscopy we acknowledge the support of  G. Schoehn  at the Grenoble FRISBI/Instruct-ERIC electron microscopy platform,  F. Weiss  and  W. Hagen  of the cryo-electron microscopy platform of the  European Molecular Biology Laboratory  ( EMBL, Heidelberg ) and  G. Pehau-Arnaudet ,  M. Nilges  from the  UBI facility (Institut Pasteur, Paris). The Falcon II detector at the  UBI  facility was financed by the " Equipement d'excellence CACSICE " and the Grenoble Instruct-ERIC EM platform acknowledges support from the  FRM  and  GIS IBiSA. Access to the EMBL cryo-electron microscopy facility was supported by  iNEXT  (project number  653706 ), funded by the  Horizon 2020 program  of the  European Union. We further acknowledge the Cell and  Tissue Imaging  ( PICT IBiSA, Institut Curie ) platform supported by  France-BioImaging  ( ANR10-INBS-04 ).
N. D. F was funded by post-doctoral fellowships from the  Institut Curie , the  Fondation pour la Recherche Médicale and Marie Curie  actions (MSCA-IF-2016 # 751715  (ESCRT model)). E. M. L was supported by a post-doctoral fellowship from  ANR  ( ANR-15-CE11-0027-02 ). M. A. was funded by the  Université Pierre et Marie Curie/Sorbonne Université, Doctoral school "Physique en Ile de France"  ( ED-564 ) and the  Fondation pour la Recherche Médicale. P. B. is a member of the  CNRS consortium CellTiss. P. B. ,  S. Man , A. B. , A. C. are members of the  Labex CelTisPhyBio  ( ANR-11-LABX0038 ) and  Paris Sciences et Lettres  ( ANR-10-IDEX-0001-02 ).
Introduction: Patients with ankylosing spondylitis (AS) are burdened with symptoms impacting work productivity measured by presenteeism, absenteeism, overall work impairment, and activity impairment. Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been demonstrated to improve disease signs and symptoms in two phase 3 trials of AS. This study investigated for 52 weeks the effect of ixekizumab treatment on work productivity in patients with active AS. Methods: COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled trials investigating the efficacy of ixekizumab 80 mg every 4 weeks (Q4W) and every 2 weeks (Q2W) in patients with AS naı ¨ve to biologic diseasemodifying antirheumatic drugs (bDMARDs; COAST-V) or who were inadequate responders or intolerant to tumor necrosis factor inhibitors (TNFi; COAST-W).
Study Design Descriptions of the designs of the COAST-V and COAST-W trials have been published previously  [3, 8]. COAST-V and COAST-W were phase 3, multicenter, randomized, double-blind, placebo-controlled trials conducted at 84 and 106 sites in 12 and 15 countries, respectively, across the regions of North America, South America, Europe, and Asia. COAST-V and COAST-W were registered at ClinicalTrials. gov (NCT0269785 and NCT2696798, respectively). Ethical review boards approved COAST-V and COAST-W at each site before the trials began. Procedures involving human participants were performed within the ethical standards of the institutional and national research committees at all sites. Both trials were conducted in accordance with the standards of the Declaration of Helsinki of 1964 and its later amendments.
Both trials were conducted in accordance with the standards of the Declaration of Helsinki and its later amendments. All patients gave written informed consent before undergoing procedures related to the trials. The master ethics committee was Schulman Associates IRB, Cincinnati, OH, USA; complete listings of sites and investigators are available in the supplements of previously published results from COAST-V and COAST-W  [3, 8, 9]. Data Availability. The datasets analyzed in this study are available from the corresponding author upon reasonable request. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4. 0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
ACKNOWLEDGEMENTS The views expressed are those of the author and not necessarily those of the (UK) National Health Service (NHS), the  NIHR , or the (UK) Department of Health. Funding. Eli Lilly and Company  provided funding for the sponsorship for this study and the journal's Rapid Service Fee. All authors had complete access to the data used in this study and take full responsibility for the integrity of the data and accuracy of the data analysis. Medical Writing and  Editorial Assistance. Nicole Lipitz of Syneos Health  provided writing and editorial assistance with funding provided by  Eli Lilly and Company.
sEVs were then resuspended in a solution of 40 % iodixanol in sucrose and the last purification step was carried out by ultracentrifugation on a discontinuous iodixanol/sucrose gradient (10 to 40 % iodixanol) with deposition of the sEVs on the bottom of the tube, during 18 h at 100,000 g (rotor SW41Ti, acceleration 5, no brake). The fractions 2+3 of the six fractions harvested were then pooled and washed in 25 ml PBS. After a last ultracentrifugation for 1 h at 100,000 g (Rotor SW32Ti, with maximal acceleration and brake), the pellet was resuspended in PBS, in a volume proportional to the weight of tissue (1 µl PBS per 1 mg tissue). We submitted all relevant data of our experiments to the EV-TRACK knowledgebase (EV-TRACK ID: EV200049) and obtained an EV-METRIC score of 100 %  [41].
Nanoparticle tracking analysis sEV preparations were diluted 1:100 in filtered PBS (0. 2 µm) and tracked using a NanoSight LM10 (Marvern Pananalytical) equipped with a 405 nm laser. Videos were recorded three times during 60 s for each sample at constant temperature (22 °C) and analyzed with NTA Software 2. 0 (Malvern instruments Ltd). Data were analyzed with Excel and GraphPad Prism (v8) softwares.
Grids were incubated with Protein A-Gold 10 nm (Cell Microscopy Center, Department of Cell Biology, Utrecht University). A second fixation step with 1 % glutaraldehyde in PBS was performed. Grids were stained with uranyl acetate in methylcellulose. preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this this version posted December 17, 2020. ; https://doi. org/10. 1101/2020. 11. 30. 402693 doi: bioRxiv preprint 11 All samples were examined with a Tecnai Spirit electron microscope (FEI, Eindhoven, The Netherlands), and digital acquisitions were made with a numeric 4k CCD camera (Quemesa, Olympus, Münster, Germany). Images were analysed with iTEM software (EMSIS) and statistical studies were done with Prism-GraphPad Prism software (v8).
Next, we examined the impact of hCMV infection on the secretion and characteristics of placental sEVs. Placental explants were infected by the VHL/E clinical strain overnight, extensively washed and maintained in culture during two weeks to favor virus dissemination, as already described by our team  [31]. To monitor virus release into the culture medium, we sampled one aliquot of histoculture supernatant after two medium renewal steps (corresponding to virus released between days 7 and 11), which was analyzed by qPCR. Placental explants displayed active viral release, with hCMV titers in the supernatant comprised between 1. 05 10 4 and 1. 53 10 7 copies/ml, the median lying at 3. 04 10 5 copies/ml (Figure  6A ). Importantly, these titers were indeed due to virus release and did not correspond to remaining inoculum, since no viral genome could be detected by control qPCR experiments using UV-irradiated virus (data not shown).
ACKNOWLEDGMENTS We thank the medical and paramedical staff of the gynecology unit at  Paule de Viguier Hospital , who allowed us to have access to the samples, as well as the patients who agreed to participate in the study. We also warmly thank  Louis Bujan  and  Mélanie Aubry , from the  Germethèque , for their help and professionalism, and  Christian Sinzger  who kindly provided us with the hCMV strain and gave us precious advice for its production. We greatly thank  Benjamin Rauwel ,  Maryse Romao ,  Catherine Mengelle ,  Francine Chauvrier ,  Philippe Verdy ,  Nicolas Kopf  and  Matthieu Barbet , as well as the whole ViNeDys team, for their technical preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
assistance and their numerous advice and discussions which allowed the progress of this work. Our thanks also go to  Anne-Laure Iscache ,  Valérie Duplan-Eche  and  Fatima L'Faqihi-Olive , from the cytometry facility of the  Center for Pathophysiology of Toulouse Purpan , as well as to  Florence Capilla  and  Annie Alloy , from the histology facility Gentoul Anexplo. We also thank  Laurence Nieto  and  Evert Haanappel  from the  Institute of Pharmacology and Structural Biology , who allowed us to have access to the Nanosight device, and for their many advices. This project has received financial support from the  French Society of Neonatology , the  French Biomedicine Agency , the  Réseau Mère-Enfant de la Francophonie. Our work was also financially supported by institutional grants from  Inserm ,  CNRS  and  Toulouse 3 University.
This project is part of the doctorate thesis of  Mathilde Bergamelli , who was funded by the  Ministry of Education and Research (MESR). The TEM experiments were performed on  PICT-IBiSA, Institut Curie, Paris , member of the France-BioImaging national research infrastructure, and were supported by the  French National Research Agency  through the  "Investments for the Future" program  ( France-BioImaging ,  ANR-11-INSB-04 ), supported by the  CelTisPhyBio Labex  ( N° ANR-11-LB0038 ) part of the  IDEX PSL  ( N°ANR-10-IDEX-0001-02 PSL ).
Transcriptomic Analysis RNA samples were subjected to GeneChip hybridization on the Mouse Genome 430_2. 0 Array (Thermo Fisher Scientific) following the Affymetrix two-cycle labeling protocol. Affymetrix MIAME-compliant data have been made available through Gene Expression Omnibus databases (www. ncbi. nlm. nih. gov/projects/ geo/, accession: GSE144039). Data processing, background correction, normalization, and signal quantification were carried out using RMA algorithm using the Bioconductor "affy" package version 1. 62. 0  (41). Differential expression was determined using R version 3. 6. 1 and the Bioconductor limma package version 3. 40. 6  (42). Raw p-values were adjusted for multiple testing using the Benjamini and Hochberg algorithm, and probesets with an adjusted p-value lower than 5% were considered differentially expressed.
Gene Ontology Analysis Raw probe-set identifiers were translated into ENTREZ prior to the enrichment analysis since gene-sets are defined by lists of ENTREZ gene identifiers. Additionally, ENTREZ genes linked to several probe-sets were associated with the probe-set having the most variable expression across replicates. Functional geneset enrichment analysis was performed using the Fisher statistical test for the over-representation of differentially expressed genes (adjusted P-value lower than 5%). The genes lists were used to interrogate the gene-set collection of Gene Ontology (GO) annotations selected from the Molecular Signatures Database MSigDB v6. 2  (43). Only gene-sets with an FDR lower than 0. 05 were considered significantly enriched in differentially expressed genes.
Network Analysis Networks shown in Figure  7  were derived from the String Database (https://string-db. org) with text mining, neighborhood, experiments, gene fusion, databases, co-expression, and cooccurrence as active interaction sources. Network representation was performed with Cytoscape (V3. 7. 1). Network edges correspond to active interactions and are depicted as gray lines, whereas black arrows correspond to molecule interactions verified in the literature. The list of transcription factors, their co-regulators and epigenetic factors was created manually from different web sources (AnimalTFDB/OMICS_01856, Riken Transcription Factor Database, TRRUST v2, and mTFkb) (44-46) (Supplementary Table  1 ).
Following incubation with the appropriate peroxydase conjugate secondary antibodies, membranes were revealed by SuperSignal West Pico reagent (ThermoFisher Scientific) in a high-resolution PXi machine (Syngene). Relative protein expression was calculated by densitometric analysis using the ImageJ software. The integrated density was measured on scanned gels with inverted images free of pixel saturation using a region of interest for each specific band. For every band, the ratio between the values obtained for the target protein and the β-actin normalization control was calculated and fold changes calculated using the control sample as calibrator, control values of uninfected and unstimulated samples being set to 1.
Cytokine/Chemokine Profiling and Quantitation in Culture Supernatants Cytokine/chemokine profiling was performed by the mouse XL cytokine array kit (R&D Systems) according to the manufacturer's instructions. Membranes were revealed by SuperSignal West Pico reagent (ThermoFisher Scientific) in a high-resolution PXi machine (Syngene). Semi quantitative analysis was performed with the Quickly & Easily Process Proteome Profiler TM Antibody Arrays software (R&D Systems) on the membrane scans. IL-1β quantification in the supernatants was performed by using the mouse instant ELISA kit (eBioscience) following the manufacturer's recommendations.
FUNDING This work was supported by grants from  INSERM ,  CNRS ,  Université de Nantes ,  Fondation pour la Recherche Médicale  ( FRM DEQ20170839118 ),  Ligue Contre le Cancer   AO GO2019  ( Côtes d'Armor, Loire-Atlantique ),  Association pour la Recherche contre le Cancer  ( PJA20191209404 ). This work was realized in the context of the  LabEX IGO program , supported by the  National Research Agency Investissements d'Avenir via the program   ANR-11-LABX-0016-01.
Cohort of cord blood-grafted patients The expression of CD45RC on PBMCs was analyzed from cryopreserved samples among a cohort of 88 recipients of an unrelated double cord blood transplantation (UCBT). All recipients were included in a clinical trial assessing the role of double UCBT in patients with de novo or secondary AML aged between 15 and 65 years. 19  For mouse cells, splenocytes or PBMCs were stained with anti-CD3 (145-2C11), anti-CD4 (RM4-5), anti-CD25 (PC61), anti-B220 (RA3-6B2), anti-CD19 (ID3), anti-CD49b (DX5), anti-CD11c (HL3), anti-CD11b (M1/70), anti-Ly6c (AL-21), and anti-CD45RC (DNL1. 9) mAbs from BD Biosciences. Cells were further fixed, permeabilized, and stained with anti-Foxp3 mAb (MF23; BD Biosciences). The fluorescence was measured with a FACS-Canto II flow cytometer (BD Bioscience); FlowJo software was used to analyze data.
Cells were first gated on their morphology and then dead cells were excluded by staining with fixable viability dye. For human cells, 50 mL or 100 mL of fresh EDTA whole blood were stained with combinations of appropriate mAbs (supplemental Tables  2  and 3 ), followed by erythrocyte lysis (versalyse; Beckman Coulter). After washing, cells were analyzed on a Navios flow cytometer and data analyzed using Kaluza software (Beckman Coulter) and FlowJo software.