dataesr/scientific-paragraphs-categorization huggingface dataset:
2016 ). G. Cova  and  M. -C. Deau  received predoctoral fellowships from the  IGBMC International PhD Programme  funded by the  ANR  grant  ANR-10-LABX-0030-INRT , and the  FRM. C. Taroni  was supported by predoctoral funds from the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Sklodowska-Curie  grant agreement  813091. G. Cova  received postdoctoral funding from the  ANR  grant  ANR-17-CE15-0023-01. Q. Cai received a  Fondation ARC predoctoral fellowship  and postdoctoral funding from the  INCa  grant  PLBIO-2015-114.
05). The numbers above each bar indicate the number of Helios-bound peaks (top) within the total number of peaks in the subset (bottom). Hypergeometric test: *, P < 0. 02; ***, P < 10 -10. (C) Volcano plots showing log2FC versus -log2(adj p) for Helios-bound MkP and MPP4 genes or a set of random genes. Red dots highlight regions for which -log2(adj p) was >3. 5. (D) Integrative genome viewer screenshots of representative platelet genes. Shown are ATAC-seq signals in WT and KO LSK cells and Helios, Gata2, and Runx1 binding in HPC7 cells (Gata2 and Runx1 data are from the GEO dataset GSE22178). Boxed regions belong to the regions selected in C as having significant increases of ATAC-seq signals in KO cells. (E) Seq-miner heatmap showing 4,370 regions with significantly increased ATAC-seq signals in KO versus WT LSK cells (adj P < 0.
Molecular modelling support for the design of derivatized 5-A-RU Derivatization of ribityl hydroxyl groups by an ethinyl function as well as 5'-ethinylation were envisioned and evaluated by molecular docking. 4'-ethinyloxy-5-A-RU, 2'-ethinyloxy-5-A-RU, SRRR, and SRRS stereoisomers of 13 (13SRRR and 13SRRS, respectively) docked well to the MR1/TCR model prepared from the crystal structure of the ternary complex of 7hydroxy-6-methyl-8-D-ribityllumazine/MR1/TCR (PDB entry 4L4V  [18] ). Comparison to the ternary complex of 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) with MR1/TCR (PDB entry 4NQE  [11] ) showed perfect conservation of the 5-OE-RU binding mode by the uracil and ribityl moieties of 4'-, 2'-ethinyloxy-derivatives and 13SRRR in one of the three retained poses (Figure  2  and SM2 Figure  1 ).
MRup-regulation assay At steady state, MR1 resides in the endoplasmic reticulum (ER) of cells  [23]. In the presence of vitamin B2 derivative antigens, the formed complex exits the ER and traffics through the secretory pathway to the cell membrane leading to antigenic presentation to MAIT cells. This induces an up-regulation of MR1 at the cell surface that can be measured by flow cytometry using an anti-MR1 antibody conjugated with fluorochrome. Thus, MR1 upregulation indirectly reflects the binding of the antigens to MR1. The capacity of the two ethinyl-analogues of 5-OP-RU to up-regulate MR1 at the cell surface of WT3-m cells (embryonic murine fibroblast cells overexpressing MR1  [24] ) was assessed. Data are depicted both as percentage of MR1 positive cells (Figure  4A ) and corresponding mean fluorescence intensity (Figure  4B ) of PE-conjugated antibody anti-MR1.
X ray crystallography 12a was dissolved at room temperature in a 80/20 mixture of acetonitrile/water and was let at room temperature for solvent evaporation. After 2 days, small needles were obtained but necessarily brought to PROXIMA 2A (PX2A) beamline at the SOLEIL Synchrotron, Gif-sur-Yvette, Paris, France, for complete data collection at T = 100K. Crystal data, data collection and structure refinement details for 12a crystal model are available in the Supporting Information file but are summarized below. CCDC 1990644 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www. ccdc. cam. ac. uk/data_request/cif.
MR1 up-regulation experiments A suspension of WT3-m cells was prepared, and 100 000 cells were introduced into 96 wellsplates. The cells were incubated 3h at 37°C (5% CO2). The ligands to be tested were diluted to the desired concentrations in culture media and added into the wells. The plate was incubated for 2h at 37°C (5% CO2). Cells were detached using versene solution on ice for 10 minutes and further stained by anti-MR1-PE antibody. DAPI was used to exclude dead cells. The cells were analyzed using CytoFLEX flow cytometer (Beckman Coulter). Analysis of the data was done with FlowJo software and graphs were made using Prism 8 software (GraphPad) with a two-way ANOVA test for the statistical analysis.
DAPI was used to exclude dead cells. The cells were analyzed on CytoFLEX flow cytometer (Beckman Coulter). Activation of MAIT cells (Vβ6 + -Vβ8 + , CD4 -, CD8 +/- cells) was determined by the percentage of both CD69 and CD25 positive cells. Analysis of the data was done with FlowJo software and graphs were made using Prism 8 software (GraphPad) with a two-way ANOVA test for the statistical analysis.
Molecular modellingMolecular modeling was carried out using Drug Discovery Suite by Schrödinger Inc. in versions 2016. u3 or 2020. u1 for model visualization, ligand design and preparation, protein structure preparation, homology modeling and loop refinement, energy minimizations, molecular dynamics simulations and analyses. More specifically the programs and tools Maestro, Protein Preparation Wizard, Ligprep, Epik, Glide, PRIME, Macromodel, and Desmond were used applying standard settings and procedures unless specified otherwise [33] [34] [35] [36] [37] [38]. Implicit or explicit SPC water models were applied with force field parameters OPLS3 [40]. PDB entries 4L4V and 4NQE were prepared in the Protein Preparation Wizard by replacing missing side chains, commitment of alternative side chain conformations by visual inspection, optimization of hydrogen bonding networks with pKa calculation by Epik, and minimization of hydrogen atoms only.
Acknowledgements The author want to thank  Jean-Claude Florent  and  Bhanudas Dasari  for chemical discussions. Thomas Yvorra wants to thank the  ANR  ("In vivo analysis of MAIT cell functions in health and disease") for financial support and  Aurélie Darbois Delahousse  for training in biological experiments. We acknowledge the use of the synchrotron-radiation facility at the SOLEIL synchrotron,  Gif-sur-Yvette , France under the BAG proposal 20191181. We also thank  Dr Martin Savko  and the staff of the PROXIMA 2A beamline at SOLEIL for assistance with data collection. We also want to thank the flow cytometry core of  Institut Curie  and the  PICT-IBiSA at Pasteur Imaging Facility of Institut Curie , member of the  France-BioImaging national research infrastructure.
2. 1. 5 15 Molecular modellingMolecular modeling was carried out using Drug Discovery Suite by Schrödinger Inc. in versions 2016. u3 or 2020. u1 for model visualization, ligand design and preparation, protein structure preparation, homology modeling and loop refinement, energy minimizations, molecular dynamics simulations and analyses. More specifically the programs and tools Maestro, Protein Preparation Wizard, Ligprep, Epik, Glide, PRIME, Macromodel, and Desmond were used applying standard settings and procedures unless specified otherwise [33] [34] [35] [36] [37] [38]. Implicit or explicit SPC water models were applied with force field parameters OPLS3 [40]. PDB entries 4L4V and 4NQE were prepared in the Protein Preparation Wizard by replacing missing side chains, commitment of alternative side chain conformations by visual inspection, optimization of hydrogen bonding networks with pKa calculation by Epik, and minimization of hydrogen atoms only.
Materials and Methods Data on patients with advanced melanoma (N = 1862) from March 2016 to March 2021 were obtained from the RicMel database, a French national multicentric database dedicated to the follow-up of MM patients. Patients who received intravenous anti-PD-1 therapy or a combination of PD-1 and anti-CTLA4 were selected, and the occurrence of irAEs, the number of perfusions and overall survival rates were analyzed. The RicMel database (Clinical Trials n •. NCT03315468) gathers data from 49 participating centers in different French regions. It received ethics committee approval on February 9th, 2012 (no. 12. 108) from the Independent Ethics Committee in Paris and received authorization from the French Data Protection Agency (CNIL, DR-2012-259, 28 May 2012). The inclusion criteria were as follows: -Patients with unresectable stage IV MM; -Patients treated with anti-PD-1 or combination therapy -Patients who experienced grade III-IV irAEs with the administered IT.
RicMel is a declarative French database. All irAEs have been previously studied by local pharmacovigilance surveys to rule out the imputability of immunotherapy from the medical field. After screening the RicMel database, complementary medical data were collected for the included patients at the Nantes University Hospital. We reported 79 grade III/IV irAEs due to PD-1i according to standard guidelines, such as the CTCAE (Common Terminology Criteria for Adverse Events). The grading of irAEs was determined by treating physicians (dermatologists and/or oncologists) and reviewed by a physician from the RicMel database. All baseline characteristics are summarized in Table  1. Details of 15 grade III/IV irAEs occurring after at least one year of ICI initiation are listed in Table  3  with details on the management of irAEs and recovery time.
Tissueresident memory CD8 + T cells (T RM cells) promote a durable melanoma-immune system equilibrium that is confined to the epidermal layer of the skin  [41]. This explains the higher incidence of irAES associated with SSM on the one hand; on the other hand, it leads to better PFS and OS outcomes among SSM patients. As this was a monocentric study, our results are not powerful enough to make recommendations. However, our results confirm the necessity of performing a larger multicentric cohort study analyzing data from all participating centers from the national RicMel database.
Patients/population The pathologic database of the Department of Pathology of Tenon University Hospital (Assistance Publique des Hôpitaux de Paris, Sorbonne University Paris) was searched for all cases of histologically diagnosed OCs (including primary OCs with and without synchronous EC) from January 2005 to July 2017. All the patients had been treated at the ovarian cancer expert center in Tenon University Hospital. Exclusion criteria were tumor samples from other hospitals (cases sent for review) absence of formalin fixed and paraffin embedded (FFPE) tumor block in archives, no primary tissue tumor available, or absence or insufficient FFPE tumor material. Tissue samples were excluded after neoadjuvant chemotherapy. Borderline ovarian tumors were excluded. We recorded the clinicopathologic features, including histologic subtypes, tumor stage and grade, lymph node involvement, recurrence-free survival (RFS) and overall survival (OS) from the medical and pathologic reports.
Tissue microarrays The tissue samples were used for the tissue microarrays (TMA). The arrays were constructed with a 1 mm punch on semi-automated Tissue Arrayer MiniCore ® (Excilone ® Alphelys ® ). Each selected/donor block was arrayed in triplicate including three tumor cores. The grid layout was designed using TMA designer software ® and converted into a Microsoft Excel file. A 3 µm H&E-stained section was reviewed to confirm the presence of tumor sample. A histospot was considered unsuitable for analysis when it was completely absent, contained no tumor tissue (sampling error), or contained too few tumor cells for analysis (less than 10% of the surface area occupied by tumor cells was considered uninformative). Two cores with tumor cells were considered to be available for evaluation.
Characteristics of the study population Between 2005 and 2017, of the 184 patients with OC included in the database, 48 had bilateral OC. Among them, 13 patients had synchronous or metachronous uterine carcinoma. Forty-four tissue samples were excluded after neoadjuvant chemotherapy. Therefore, the study population included 232 ovarian tumors. After review and addi-Table  1. Epidemiologic and histologic characteristics of the population. Clinical and histological parameters are summarized in Tables  1  and 2. The most common histologic subtypes were serous carcinomas (50. 5%) including 82. 8% of high-grade serous carcinoma (HGSC) and 17. 2 % of low-grade serous carcinoma (LGSC). EC was the second most common subtype (20. 1%). CCCs were diagnosed in 13. 6% of patients. Finally, sex cord stroma tumor (SCST) and germ cell tumor (GCT) constituted 3.
Statistical analysis The descriptive analysis was conducted based on the demographic, socio-economic, and clinical variables in each procedure group. Comparability of the groups was evaluated using Chi-2 tests, ANOVA tests for categorical variables whereas t-Student tests for continuous variables. The comparison between the rate of screening completion and the number of cytological lesions was conducted using logistic and Cox regressions. All analyses were repeated with another sample that only included data from CASO/CAOA programmes. Statistical analysis was done using the software Stata 15  [20].
To limit these potential sources of bias, we decided to conduct a supplementary analysis that only included data from the CASO/CAOA (77% of the sample), obtaining very similar results to the full dataset. The study was underpowered for the outcome "proportion of cytological abnormalities", as the study had to stop before sample size completion due to budget constraints. In addition, it would have been better to measure the completion rate based on the number of retrieved results, which would have ensured that the women knew their status. Unfortunately, this information was available for the results of the HPV tests (which were conducted and collected within MdM facilities), but not for the results of the PS exams (which were conducted and collected in a variety of partner facilities). Finally, it would be beneficial to offer a holistic SRH strategy to these populations, including vaccinations and testing for other STIs, such as HIV and hepatitis.
Patients and Tumor Samples The study was reviewed and approved by the Montpellier Cancer Institute Institutional Review Board (ID number ICM-CORT-2019-27). Samples were selected from a prospective collection of breast cancers surgically removed at the Institut du Cancer de Montpellier (France) between 2002 and 2010 and annotated in a dedicated prospective database (tumor biobank number BB-0033-00059). Only tumors from patients who did not have a history of another invasive cancer in the previous 5 years, without known germline BRCA mutation and with unifocal, unilateral, untreated, non-metastatic breast cancers and with ER and PR negativity (defined as <10% of tumor cells stained by IHC)  [34]  and HER2 negativity (defined as IHC 0/1+ or 2+ and negative fluorescent/chromogenic in situ hybridization), were selected for this study.
The CD11b-, CD66b-and CXCR2-immunostained TMA sections were digitalized using a NanoZoomer slide scanner system (Hamamatsu Photonics, Hamamatsu City, Shizuoka Pref. Japan) with a 20× objective. Quantification of IHC staining was performed by image analysis using HistoLab ® Image Analysis Software (Microvision, Evry, France) as previously described  [18]  by delineating the invasive component in each sample core as a region of interest (ROI). Density of immune-reactive cells in the ROI, recorded as the number of positive cells per cm 2 , was calculated for each tumor sample and finally matched to clinicopathological data. Missing TMA cores, those with folded tissue or demonstrating significant artifacts were not scored.
Data Availability Statement: The dataset is owned by ANRS (France REcherche Nord&Sud Sida-hiv Hépatites), an autonomous agency within Inserm. Data requests may be submitted to the data monitoring and analysis centre of the study and must be approved by the French computer watchdog authority, la Commission Nationale de l'Informatique et des Libertés (CNIL). Data requests may be sent to Lambert Assoumou (lambert. assoumou@iplesp. upmc. fr).
Results The search strategies identified four guidelines from MEDLINE  [7, [17] [18] [19] , two from Google Scholar  [20, 21] , one from the Haute Autorité de Santé (HAS)  [22] , one from the National Institute for Health and Care Excellence (NICE)  [23] , two from. The Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)  [24, 25] , one from the Belgian Antibiotic Policy Coordination Committee (BAP-COC)  [26]  and one from the International Lyme and Associated Diseases Society (ILADS)  [27]. The remaining number of guidelines found in each database after removal of duplicates and then selected for further review and met the inclusion criteria are shown in Figure  1. Eleven guidelines were developed by official academic societies  [7, [17] [18] [19] [20] [21] [22] [23] [24] [25] [26]  and one by a non-official organisation, the ILADS, defined as a 'transdisciplinary medical association' of physicians and researchers working on Lyme and tick-borne diseases (Table  1 )  [27].
Data Sources and Search Strategy We performed a systematic review of guidelines on LB using the PRISMA method  [68]. We searched MEDLINE, Google Scholar and databases of the National Institute for Health and Care Excellence (NICE, https://www. nice. org. uk/ accessed on 30 April 2021), The Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, https://www. awmf. org/ accessed on 30 April 2021), Haute Autorité de Santé (HAS, https://www. has-sante. fr/ accessed on 30 April 2021) and the International Lyme and Associated Diseases Society (ILADS, https://www. ilads. org/ accessed on 30 April 2021). We included guidelines from 2014 to 2020, as the majority of the guidelines have been updated recently. Only the most recent guidelines from the same authors or organizations were included in the analysis.
Data Extraction of Guidelines and Analysis After quality appraisal, AR and SN independently extracted information and checked the data from each guideline. A standard form was designed for data extraction covering the country, publication year, level of scientific evidence, clinical stage of LB and antibiotic therapy (molecule, duration, and dosage). Descriptive analysis of the quality of the guideline included median and interquartile range (IQR). STATA version IC 16 (College Station, TX, USA) was used for all statistical analyses. No ethical approval or consent was needed for this study.
, 2019). The signal was detected by a 4 laser Fortessa® flow cytometer (Becton Dickinson). Analyses were carried out using FlowJo® software. Three µm sections of paraffin-embedded samples were analyzed using a Ventana Discovery Ultra automated staining instrument (Ventana Medical Systems), according to the manufacturer's instructions. Briefly, slides were de-paraffinized, the epitope retrieval was performed with the reagents provided by the manufacturer, the endogenous peroxidase was blocked and the samples were incubated with the appropriate antibodies for 60 min at 37°C. Signal enhancement for Caspase 3 and Ki67 antibodies was performed either with the OmniMap anti-rabbit detection kit or by the Discovery HQ conjugated anti-rabbit IgG followed by Discovery amplification anti-HQ HRP Multimer, according to the manufacturer's instructions.
Slides were incubated with DAB chromogen and counterstained with hematoxylin II for 8 min, followed by Bluing reagent for 4 min. Brightfield stained slides were digitalized with a Hamamatsu NanoZoomer 2. 0-HT scanner and images were visualized with the NDP view 1. 2. 47 software except for the MFG-E8 staining, for which slides were digitally processed using the Aperio ScanScope (Aperio). Nodule size was drawn by hand in HALO TM image analysis software (Indica Labs) and an algorithm was designed with the Multiplex IHC v1. 2 module to quantify the percentage of positive cells per mouse, as indicated in figure legends.
Software The following open-source code and software were used in this study: R (v. 3. 5. 1), Default settings were used for all GSEA analyses. R package DESeq2 (v. 1. 22. 1), R package heatmap (v. 1. 0. 10) and R package  VennDiagram (v. 1. 6. 20)  were also used. Graphpad prism v8 was used to make graphs and for statistical analyses.
Acknowledgments This work was supported by the grant HTE from  ITMO Cancer  (to UH), from the  Association Française pour l'Etude du Foie (AFEF , to DG) and from  SIRIC Montpellier Cancer  (to UH). AL received support from the  University of Montpellier  and from the  Fondation ARC and SIRIC Montpellier Cancer. LA, SV and CR are supported by the  Dutch Cancer Society  ( KWF 12049/2018-2 ),  Oncode Institute  and the  Center for Cancer Genomics  (CGC. nl). We acknowledge the  "Réseau d'Histologie Expérimentale de Montpellier" -RHEM  facility, supported by  SIRIC Montpellier Cancer  (Grant  INCa_Inserm_DGOS_12553 ), the  European regional development foundation  and the  Occitanie region (FEDER-FSE 2014-2020 Languedoc Roussillon ), for the histological analyses. We acknowledge the  MGX facility  for the RNAseq analysis, and the  MRI  imaging platform.
MBMD is a self-report inventory containing 165 true-false items. It provides scales to assess psychobehavioral factors, such as negative health habits, psychiatric indications, coping styles, stress moderators, treatment prognostics, and management guides. The scale aimed to identify attitudes that may affect health of the patient. At the next visit, after giving consent, the patient told her life history during a structured interview. The Holmes and Rahe Social Readjustment Rating Scale  [12]  was used to score each stressful life event in "Life Change Units" (LCU). The life events and LCU were collected in an Excel file and classified chronologically. LCU applied to life events for 1 year were summed to assess the annual stress score. In parallel, the medical data of the electronic health records were chronologically integrated in the Excel file to establish a comprehensive dermatological history of the mastocytosis.
In the Fig. 1  Medical data and stressful life events. Horizontal axis corresponds to the age of the patient (in years). Green triangles represent annual stress scores. Holmes and Rahe Social Readjustment Rating Scale was used to score each stressful life event (in "Life Change Units" LCU). Scores were calculated after the clinical interview of the patient. LCU applied to life events during 1 year were summed to assess the annual stress score. Red lines indicate the periods of cutaneous events recorded in the medical chart. Annual stress scores of life events were low (<50) during childhood. We did not have documentation about the medical status during this period. At the age of 22 years, two major stressful life events occurred: business readjustment (39 LCU) and divorce (65 LCU), totaling a global stress score of 104 LCU.
Acknowledgments: We express our deep gratitude to the  University of Sharjah  for the financial and technical support for this research and to all volunteer participants in this study from  Al Chifaa Hospital and Al Mazloum Hospital ,  North Lebanon. Special thanks are credited to  Ibtihal Al-Qassam of laboratory medicine department of Dar Al Chifaa Hospital, Tripoli, Lebanon , who enormously helped the research assistant in collecting the stool samples.
The amounts of infectious particles (PFU/mL) released in the lower chamber were assessed at 2, 8, 12, and 24 hpi by plaque assay. c, d FNV multiplication in endothelial cannot be detected before 12 h after virus inoculation of the upper compartment of the mBBB. The relative amounts of cell-associated genomic and antigenomic RNA were determined by RT-qPCR analysis. Amounts of viral RNA were expressed as genome equivalents (Geq, c) or antigenome equivalents (AGeq, d) per µg of total cellular RNA. Statistical analysis: Two-way ANOVA with post hoc Sidak's test (**p < 0. 01; ***p < 0. 001 ****p < 0. 0001). Data in all bar graphs were means ± SD of three independent experiments (N = 3) performed in triplicate (n = 3). Dashed lines indicate the limit of detection.