dataesr/scientific-paragraphs-categorization huggingface dataset:
Among the 63 patients recruited, a few received treatments consisting in either Darbepoietin (EPO, n=4) or Eltrombopag (TPO, n=1) without obvious effect on immune cells, or the immunomodulating drugs Lenalidomid (n=4) or the glucocorticoid Prednisone (n=4). The second cohort was composed by MDS patients recruited in the clinical trial #NCT02985190 (sponsored by Groupe Francophone des Myélodysplasies [GFM]) and repeatedly treated with azacitidine at 75mg/m²/j subcutaneously daily for 7 days every 4 weeks  29  (Supplementary Table  8 ). In addition, PBMC samples from 23 healthy individuals (HD) were collected through the EFS (Etablissement Français du Sang) (median age = 46 [27-66]). The study was approved by the Ethical Board Ile-de-France X and conducted in accordance with Helsinki's declaration.
Flow Cytometry Analysis Frozen sternal BM aspiration and PBMCs were stained for 30min on ice  13  , with the fixable viability dye eFluor 506 and monoclonal antibodies (mAb) listed in Supplementary Table  9. Of note, mAb used in this work to detect KIR molecules on cell surface were able to identify KIR2DL1, KIR2DL2/DL3, KIR2DL4, KIR3DL1/DL2, KIR3DL1/DS1, KIR2DL5 and KIR2DS4 molecules. Cells were fixed in PBS with 2% of paraformaldehyde (PFA), acquired on a BD Fortessa X20 (flow cytometry core facility of Saint Louis Research Institute, Paris, France) (Supplementary Fig. 9 ). For intracellular staining, Foxp3 Transcription factor buffer set (eBioscence 00-5523-00) was used and data were acquired on a BD Canto II or Cytek Aurora flow cytometer. Data was analyzed using FlowJo v10. 7 software or Cytek SpectroFlo v3.
A panel of 80 genes commonly analyzed in myeloid malignancies (Supplementary Table  4 ) was examined using next-generation sequencing on an Illumina platform (Illumina, San Diego, CA, USA). Libraries were prepared from 200 ng of DNA using a custom probes panel for capture of all coding sequences (SureSelectXT Target Enrichment System, Agilent, Santa Clara, CA, USA). Sequencing data were analyzed for variant calling using an in-house pipeline. High-probability pathogenic mutations were retained based on the available databases for SNPs, somatic mutations in cancer, prediction algorithm and frequencies of variant reads. Overall, a mean coverage of 851 reads/amplicon was achieved allowing reliable detection of low burden mutations. Lolliplot has been realized using the St Jude protein paint software available online at (https://proteinpaint.
stjude. org/) (Fig. 3A )  44. Major domains of TET2 protein were determined based on the work by Hu et al  45. The mutational landscape was established using cBioPortal Cancer Genomics Portal OncoPrinter software available online at (https://www. cbioportal. org/) (Supplementary Fig. 4 ). RRBS was performed by Diagenode (Seraing, Belium) on dry samples of NK-and T-cell sorted from 5 MDS patients according to the manufacturer procedure. RRBS data are available on the Gene Expression Omnibus platform under the accession code GSE183020 (https://www. ncbi. nlm. nih. gov/geo/query/acc. cgi?&acc=GSE183020). 100ng of purified genomic DNA were used, including pre-RRBS quality control, enzymatic digestion and bisulfite conversion. Sequencing was performed in paired-end mode 50bp (PE50), quality control of sequencing reads was performed using FastQC, and reads alignment against human reference genome hg38/GRCh38 using Bismark v0.
Killing was quantified after 4 hours of incubation at 37°C by measuring calcein-release into supernatant. Specific killing was calculated as below: (Measured fluorescence of K562+PBMC well -Spontaneous Fluorescence)/(Maximum fluorescence -Spontaneous fluorescence)*100. For the ex vivo IFN-γ quantification, enriched NK cells from MDS patients enrolled in the NCT02985190 clinical trial  29  were cultured with PMA-Ionomycin (SIGMA, 50ng/mL and 500ng/mL respectively) for 5h at 37°C. Brefeldin A (Sigma) was added at a final concentration of 10µg/ml after 1h of incubation. The percentage of IFN-γ positive cells was estimated by flow cytometry in the CD3 -CD56 + NK cells. Spontaneous release was detected in the absence of target cells.
Statistical Analysis Data are shown as median ± interquartile range, if not otherwise specified. Cytometry analysis were extracted from FlowJo v10. 7 software and analyzed with Graph Pad Prism v8. 0 software. Unpaired statistical analyses were calculated with the nonparametric Mann Whitney test. Paired statistics analyses were calculated with the nonparametric Wilcoxon matched pairs signed rank test. The Kolmogorov-Smirnov D test was used to calculate differences between treated/transfected and control situations. Pearson coefficient (r) was calculated to evaluate significant correlation. Receiver operation characteristic (ROC) curve was realized based on TET2 mutation status and percentage of KIR2D+ NK cells. Area under the curve, confidence interval, p-value and likelihood ratio were calculated.
Acknowledgments This study was supported by a grant from the  French Ministry of Health  and the  French National Cancer Institute  (# PRT-K2017-109 ), the  Cancéropôle Ile-de-France , the  Association Laurette Fugain  (# ALF 2016-07 ), the  Association Force Hémato  (Call for projects 2017), the  Ligue contre le Cancer (Ile-de-France committee) , the  Association Saint-Louis pour la Recherche sur les Leucémies , and the  Association pour la Recherche en Immunologie Médicale et Expérimentale (ARIME). The authors want to acknowledge the support by the  "Groupe Francophone des Myelodysplasies (GFM) " in the management of the NCT02985190 clinical trial. The authors thank  Niclas Setterblad ,  Christelle Doliger ,  Sophie Duchez  from the  IRSL's Technological Platform ,  Nolwenn Legrand  from the  EFS laboratory in Nantes , as well as  Pierre De La Grange  and  Wail Zeitouni  from  Genosplice  for their technical and analytic support.
Data Availability Reduced representation bisulfite sequencing (RRBS) data that support the findings of this study have been deposited in the Gene Expression Omnibus data repository with the accession number GSE183020 (http://www. ncbi. nlm. nih. gov/geo/query/acc. cgi?acc=GSE183020). The in vitro data generated in this study are available in the Supplementary information. Sequences of oligonucleotides used for the KIR genotyping (PCR-SSP) are limited to non-commercial and research use and are available upon request to Dr K. Gendzekhadze (kgendzek@coh. org), City Of Hope Medical Foundation, 1500 Duarte Rd, Duarte, CA 91010. Source data are provided with this paper as a Source Data file.
Loops L3 and L4 are particularly mobile in our structures as indicated by high B-factors (>105 Å 2 ) for their Cα atoms (Fig. S2 ). Electron density was observed for the 8 predicted N-glycosylation sites (Fig. 1c ), allowing the modeling of at least one N-acetyl glucosamine (NAG) at each site (Fig. 2  and Fig. S3a ). Searching the PDB databank using the DALI algorithm  23  , with the RBD and its substructures as queries, did not yield any meaningful results. Comparative analyses with the available structures of the RBDs from Orthoretroviruses (Fig. S4 ) did not reveal structural similarity, either at the level of the secondary structure topology or the threedimensional fold. Therefore, the SFV RBD represents, to the best of our knowledge, an unprecedented fold. The sugar attached to the strictly conserved 8 th N-glycosylation site (N8) plays a structural role There were no major differences between the X-ray structures of RBD D and RBD G (their superposition yielded a root mean square deviation (rmsd) below 1 Å (Fig.
S5 ). The glycan moiety covers a well-conserved and hydrophobic surface (Fig. 3a, b ) and thus maintains the RBD fold and prevents aggregation, consistent with the reported misfolding and low levels of the secreted PFV SU with a mutation in the N8 site  18. N8 is the only N-glycosylation site in SU that is strictly conserved across the FV subfamily (Fig. S6 ), and the hydrophobic patch residues laying beneath it are conserved as well (Fig. 3c ). Thus, N8 likely plays an important structural role in all FV RBDs. The RBD fold is predicted to be conserved across the Spumaretrovirinae subfamily To investigate potential conformational differences between RBDs from different species, we used AlphaFold 2 (AF2)  24  software for ab initio prediction of the RBD structures from members of each of the 5 FV genera, some of which exist as two genotypes due to the modular nature of FV Env  25.
To be comparable with the RBD, the concentration for the ectodomain is calculated and plotted for the monomeric protein. Gating strategy is presented in (Fig. S13a ). Source data are provided as a Source Data file. c Binding of WT, mut1 (K342A/R343A), and mut2 (R356A/R369A) recombinant Env ectodomains to HT1080 and BHK-21 cells. SFV Env binding level to live single cells was expressed as the ratio of MFI from protein treated to untreated cells (Fig. S13b ). Mean from two independent experiments are shown. Cell HS expression levels were monitored on the day of each of the two experiments (the HS staining levels were 85. 4 and 61. 6 for HT1080 cells, 8. 40 and 2. 68 for BHK-21 cells (Fig. S13c )). Source data are provided as a Source Data file. d Binding of WT, mut1 (K342A/R343A), and mut2 (R356A/R369A) recombinant Env ectodomains to HT1080 cells, treated with heparinase or buffer, was quantified at increasing ectodomain concentrations.
Source data are provided as a Source Data file. f Binding of FVVs carrying the WT, mut1 or mut2 Env to HT1080 cells. Three batches of FVVs were incubated with HT1080 cells on ice for 1 h at different number of particles/cell ratios, before washing and quantifying the remaining vector particles by RT-qPCR. The dotted line represents the quantification threshold. The FVVs carrying the mutant and WT Envs were compared using the two-way paired t-test, with p-values indicated on the graph. Source data are provided as a Source Data file. unique FV features (assembly, particle release 36 , replication  37  ) that are not shared with Orthoretroviruses, and is not surprising considering the lack of Env sequence conservation between the Orthoretrovirinae and Spumaretrovirinae subfamilies. Structural information is available for the RBDs of some Orthoretroviruses.
Expression construct design (SFV RBD and ectodomains for HSbinding studies) A flow-cytometry assay was developed by Duda et al. to detect binding of recombinantly expressed Foamy virus Env variants to cells  18. By using a panel of SU truncations fused to the Fc region of murine IgG (immunoadhesins) the authors showed that the RBD-defined as the minimal region of the PFV Env sufficient for binding to cells-encompassed residues 225 to 555 (corresponding to residues 226 to 552 in gorilla FV RBD (GII-K74 strain, accession number JQ867464)  44  (Fig. S6 )). When designing the expression construct for SFV RBD, we also considered the secondary prediction generated by the Phyre2 webserver  45. Residue I225 was in the middle of a putative helix (residues 220-230), leading us to choose an upstream residue R218 as the N-terminus of the construct (Fig.
Recombinant SFV RBD and ectodomain production and purification For structural studies, the RBD (residues 218-552, GII-K74 strain, Env accession number JQ867464) was cloned into a modified pMT/BiP insect cell expression plasmid (Invitrogen) designated pT350, which contains a divalent-cation inducible metallothionein promoter, the BiP signal peptide at the N-terminus (MKLCILLAVVAFVGLSLG), and a double strep tag (DST) (AGWSHPQFEKGGGSGGGSGGGSWSHPQFEK) at the C-terminus  46. This plasmid was co-transfected in Drosophila Schneider line 2 cells (S2) with the pCoPuro plasmid for puromycin selection  47. The cell line has undergone selection in serum-free insect cell medium (HyClone, GE Healthcare) containing 7 μg/ml puromycin and 1% penicillin/streptomycin. For the protein production stage, the cells were grown in spinner flasks until the density reached ~1 × 10 7 cells/ml, at which point the protein expression was induced with 4 μM CdCl 2.
Crystallization Crystallization trials were performed in 200 nanoliter sitting drops formed by mixing equal volumes of the protein and reservoir solution in the format of 96 Greiner plates, using a Mosquito robot. Crystal appearance and growth were monitored by a Rock-Imager at the Core Facility for Protein Crystallization at Institut Pasteur in Paris, France  48. The native RBD D crystal used for data collection was grown in 0. 1 M Tris pH 8. 5, 3. 5 M sodium formate (NaCOOH). For the derivative data, the RBD D crystal, grown in 0. 1 M Tris pH 8. 5, 3. 25 M sodium formate, was soaked overnight in the same crystallization solution supplemented with 0. 5 M sodium iodide and directly frozen using the mother liquor containing 33% ethylene glycol as cryo-buffer. The RBD G crystals were obtained from a solution containing 0.
X-ray diffraction data collection and SFV RBD structure determination The X-ray diffraction data were collected at the SOLEIL synchrotron source (Saint Aubin, France). The native data for RBD D and RBD G were collected at 100 K at the Proxima-1  49  beamline, at wavelength of 0. 9786 Å, while the derivative (iodine-soaked) data for RBD D were collected at Proxima-2A, at wavelength of 1. 907 Å. The beamlines are equipped with the Pilatus Eiger X 16 M and Eiger X 9 M detectors (Dectris), respectively. We obtained trigonal crystals, space group 322 1 for the RBD D (2. 57 Å), P3 1 21 (later found to be P3 2 21) for the derivative RBD D (3. 2 Å), and hexagonal crystals for the RBD G protein (2. 8 Å, space group P6 1 ). Diffraction data were processed using XDS  50  and scaled and merged with AIMLESS  51.
The high-resolution cut-off was based on the statistical indicator CC1/2  52. Several applications from the CCP4 suite were used throughout processing  53. The statistics are given in Table  S1. The phases were determined experimentally by single-wavelength anomalous diffraction. The AutoSol pipeline from the Phenix suite  54, 55  was employed, using the anomalous data set, searching for iodine sites and specifying two NCS copies in the asymmetric unit (ASU). AutoSol reliably determined the substructure, composed of 20 iodine sites. The refined anomalous phases were internally used to phase the entire protein with the aid of density modification. The result of the process was a structure with a low R-factor; moreover, the density modified map showed a good contrast between the protein and the solvent and helical features clearly discernible.
SFV GII RBD fitting into PFV Env EM map The RBD fitting was performed with the fit-in-map function in Chimera suite  29  using the RBD D model (PDB: 8AEZ) and the 8. 8 Å EM map (EMD-4013) obtained for the PFV Env  13. The map used for fitting was simulated from atoms at a 9 Å resolution and data above the map contour level 0. 025, resulting in a correlation coefficient of 0. 96. To prepare Fig. 4 , a contour level of 0. 014 was chosen to allow visualization of the density for most the glycans.
A minimum of 25,000 cells were acquired on a Cyto-FLEX cytometer (Beckman Coulter). Data were analyzed using Kaluza software (Beckman Coulter). Viable single cells were selected by the sequential application of gates on FSC-A/SSC-A and SSC-A/SSC-H dot-plots (Fig. S13a ). Cells labeled with the two secondary antibodies only were used as a reference. SFV Env binding was expressed as the ratio of mean fluorescence intensity (MFI) from the cells that were incubated with the recombinant ectodomains vs. untreated cells (Fig. S13b ).
Acknowledgements This work was funded by the  'Agence Nationale de la Recherche ' ( ANR-10-LABX62-IBEID ,  Intra-Labex  Grant, M. B. ), the ' Programme de recherche transversal from Institut Pasteur'  ( PTR2020-353  ZOOFOAMENV, F. B. ), and recurrent funding from  Institut Pasteur (F. A. R, A. G. ). The funding agencies had no role in the study design, generation of results, or writing of the manuscript. We thank the staff from the  Utechs Cytometry & Biomarkers and Crystallography platform at the Institut Pasteur , the synchrotron source SOLEIL ( Saint-Aubin, France ) for granting access to the facility, and to the staff of Proxima 1 and Proxima 2A beamlines for their kindness and assistance during X-ray data collections. We are grateful to  Jan Hellert ,  Pablo Guardado-Calvo  and  Philippe Afonso  for the discussions and advice, with special thanks to  Max Baker  for reading the manuscript and English language corrections.
Data availability The data generated in this study and related to the X-ray structures determined for the SFV GII RBD D and RBD G have been deposited to the RCSB protein databank under PDB accession codes 8AEZ and 8AIC, respectively. The AF2 models of FV RBDs have been deposited to the Model Archive database, with the following accession codes: gorilla (genotype II, accession code: ma-5hiw1), gorilla (genotype I; accession code: ma-sln9b), prototype Foamy virus (chimpanzee, genotype I; accession code: ma-ogxjm), Western chimpanzee (genotype I; accession code: ma-zilao), Central African chimpanzee (genotype II, accession code: ma-u3aws), African green monkey (accession code: ma-mf4i2), orangutan (accession code: ma-kae1t), macaque (accession code: ma-eolif), marmoset (accession code: ma-4q50y), bovine (accession code: ma-ad22f), equine (accession code: ma-iodkg), and feline (accession code: ma-ocsub).
Infection Assay SARS-CoV-2 was handled at biosafety level 3. We used the SARS-CoV-2 Wuhan strain (2019-hCoV/Japan/TY/WK-521/2020, GISAID ID: EPI_ISL_408667), Delta variant AY. 122 (hCoV-19/Japan/TY11-927/2021, GISAID ID: EPI_ISL_2158617), Omicron variant BA. 1. 18 (hCoV-19/Japan/TY38-873/2021, GISAID ID: EPI_ISL_7418017), an E406W variant that is resistant to casirivimab/imdevimab (REGN-COV2) antibody cocktail (the complete sequence was shown in Table  S1 )  [23] , and RDV-escape mutant R10/E796G C799F (Gen-Bank ID: LC742929)  [23, 24]. VeroE6/TMPRSS2 cells were inoculated with the viruses at a multiplicity of infection (MOI) of 0. 003 for 1 h and unbound viruses were removed by washing, as previously described  [25, 26]. Cells were cultured for an additional 24 h and the extracellular viral RNA was quantified via real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis.
Remdesivir and cepharanthine were used as positive controls for a replication and an entry inhibitor, respectively, as reported  [28, 29]. Viruses 2023, 15, x FOR PEER REVIEW 3 of 9 BA. 1. 18 (hCoV-19/Japan/TY38-873/2021, GISAID ID: EPI_ISL_7418017), an E406W variant that is resistant to casirivimab/imdevimab (REGN-COV2) antibody cocktail (the complete sequence was shown in Table  S1 )  [23] , and RDV-escape mutant R10/E796G C799F (Gen-Bank ID: LC742929)  [23, 24]. VeroE6/TMPRSS2 cells were inoculated with the viruses at a multiplicity of infection (MOI) of 0. 003 for 1 h and unbound viruses were removed by washing, as previously described  [25, 26]. Cells were cultured for an additional 24 h and the extracellular viral RNA was quantified via real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis.
Acknowledgments: We are grateful to  Astellas Pharma Inc. for providing micafungin derivatives (six compounds, including Mi-1 to Mi-6). VeroE6/TMPRSS2 cells were kindly provided by  Makoto Takeda at the University of Tokyo Graduate School of Medicine. We are grateful for the isolation of the SARS-CoV-2 clinical strains performed by the  Department of Virology I , the  Department of Veterinary Science, Center for Influenza and Respiratory Virus Research , and the  Department of Pathology at the National Institute of Infectious Diseases.
Data Collection and Clinical Assessment Demographic and baseline clinical data for the participants were collected or were determined from patients' charts at the time of enrolment. These data included: socio-demographic characteristics (sex, age, age of CAD onset, nationality, place of residence), clinical characteristics (T2D, cardiovascular disease, dyslipidemia, and hypertension), and anthropometric measurements: height (cm), weight (Kg) and BMI (kg/m 2 ). In addition, patients' smoking history and medication use were retrieved from the patient's chart. Patients were considered to have hypertension if they were taking antihypertensive drugs or had been so identified by their physician in their medical chart. Patients were considered diabetic if they were taking medication to reduce their blood sugar or if their physician had identified them as so in their medical chart.
Genotyping DNA was extracted using the whole blood sample collected and subjected to genotyping using Illumina Human610-Quad BeadChip (Illumina, San Diego, CA, USA) and Illumina Human660W-Quad BeadChip (Illumina, San Diego, CA, USA), as described by Hager et al 2012. 27 Among the study population, 1394 patients from Stenosis Group, and 705 patients from Stenosis Group had genotyped data available and were included in the genetic association using PLINK. 28 Using PLINK, quality control (QC) was applied, and variants were filtered out. Sex checks were performed using PLINK and variants were excluded for having >5% missing genotyping rates and <1% MAF (minor allele frequency), and for failing HWE (Hardy-Weinberg Equilibrium) test (P > 0. 05).
Statistical Analysis All statistical analyses were processed by the R package (R version 4. 1. 2). Categorical variables were displayed as counts and percentages. Normally distributed continuous data were presented as mean ± standard deviation (SD). In the univariate analysis, continuous data were analyzed by one-way ANOVA while the categorical data were compared using the χ 2 test. Differences with P-value <0. 05 were considered statistically significant. Binomial logistic regression was applied to test the association between restenosis and the risk factors such as T2D, hypertension, dyslipidemia and low HDL (defined as HDL < 40 mg/dl, HDL < 40 in men and HDL < 50 in women  29  ) after adjusting for age. In addition, the association of individual SNPs with the risk factors was tested in women and in men.
Association analyses with restenosis of 44 SNPs previously associated with CAD or T2D were performed using PLINK 1. 9 (www. cog-genomics. org/plink/1. 9/) in R language. These SNPs were specifically selected for this nested case-control study to investigate their association with restenosis. Odds ratios (OR) were adjusted for age and/or sex and were reported, OR greater than 1 implies that the mutant allele is associated with increased risk of restenosis. Allele frequencies among Restenosis and Stenosis Groups were reported. In addition, associations between the SNPs and restenosis were assessed among men and women. The Hardy-Weinberg Equilibrium (HWE) was tested using the χ2 test, the distribution of alleles was considered in agreement with HWE when P-value is more than 0. 05.
Depending on the outcome, cells were incubated 3 or 24 h with increasing concentrations of cQ-f (J774 macrophages: 5, 10, 20, 40 cm 2 / ml; primary macrophages: 1, 5, 10, 20 cm 2 /ml). J774 exposure was carried out in presence of cytochalasin D alone (Cyt D), cytochalasin D + NSA (Cyt D + NSA), and NSA alone (NSA). Plasma membrane lysis (24 h) was evaluated by extracellular LDH activity (mU/ ml) (a, c, f). Extracellular (24 h) and intracellular (3 h) levels of IL-1α were quantified by ELISA (pg/ml) (b, d, e, g), and cell stress (3 h) via WST1 assay (h). Determinations were performed in quadruplicate and expressed as the mean ± SEM. Data from one representative experiment out of three, which show the same trends, are depicted. Differences between groups treated only with silica and groups treated with silica + Cyt D and/or NSA, for the same dose of silica, were evaluated with one-way ANOVA, followed by Tukey's multiple comparison test.