dataesr/scientific-paragraphs-categorization huggingface dataset:
Experimental Section LiNiO 2 was synthesized by direct solid-state synthesis from NiO and Li 2 O. Several experiments were realized to optimize the Li/Ni ratio of the precursor and the temperature profile of the thermal treatment in order to have the lowest amount of nickel in the lithium sites. The best results were obtained with a 6% Li excess versus the nominal composition. Two thermal treatments (24 h at 665 °C and 24 h at 700 °C of the oxides mixture, with intermediate grinding) under oxygen flow lead to a material very close to the ideal stoichiometry. This material was characterized by powder XRD diffraction. Powder XRD was performed using a PANalytical diffractometer and Cu K radiation ( = 1. 5418 Å). Phase identification was performed using XPert HighScore software, and structural refinement using the Rietveld method on TOPAS software.
Data were collected with long acquisition in the 10-120° (2θ) range for Rietveld refinements. Synchrotron-XRD (S-XRD) powder patterns have been registered on the BL04-MSPD beamline [*] of the ALBA synchrotron at either ≈20 keV or ≈30 keV (exact wavelength determined by measuring selected peaks of silicon SRM640d NIST standard). Data were collected in Debye Scherrer mode using the position-sensitive detector MYTHEN. [64] amples for transmission electron microscopy (TEM) were prepared by dispersing the powders in dry dimethyl carbonate in an agate mortar and depositing drops of suspension onto a carbon film supported by a copper grid. TEM samples were prepared in an Ar-filled glovebox. The samples were transferred to the microscope column with a Gatan vacuum transfer holder completely excluding contact with air and moisture.
Acknowledgements The authors thank  Region Nouvelle Aquitaine  and  Umicore company  for financial support and fruitful discussions,  CELLS-ALBA  for provision of beamtime through  BL04-MSPD in house program  (proposal ID 2021035158), A. M. A. is grateful to the  Russian Science Foundation  for financial support (grant  20-13-00233 ). Access to TEM facilities was granted by the  Advance Imaging Core Facility of Skoltech, Cathy Denage  for experimental support and SEM image acquisition.
Sampling frequency was 25 Hz. Data were extracted using R software (R version 4. 0. 5, 2021-03-31, R Foundation for Statistical Computing, Vienna, Austria). The pupil diameter was recorded through a pupillometry protocol divided in two parts. The first part of the protocol assessed the melanopsin-mediated pupil response with a validated protocol previously described  (Rach et al. , 2022; van der Meijden et al. , 2015)  that included 5 min of baseline darkness, 5 min of monochromatic red light (wavelength = 630 nm, luminance = 375 cd m À2 , retinal irradiance = 14. 75 log photons cm À2 s À1 ), 5 min of post-red darkness, 5 min of monochromatic blue light (wavelength = 470 nm, luminance = 375 cd m À2 , retinal irradiance = 14. 75 log photons cm À2 s À1 ) and 5 min of post-blue darkness. The second part of the pupillometry protocol allowed to explore the pupil response to green light, which remains today poorly investigated, and included 5 min of baseline darkness (green baseline), 5 min of monochromatic green light (wavelength = 520 nm, luminance = 375 cd m À2 , retinal irradiance = 14.
FU N D I N G I N FO R M ATI O N This work was supported by  Instituto de Salud Carlos III (ISCIII)  of the  Spanish Ministry of Science and Competitiveness  (grants co-funded by the  European Regional Development Fund)  through the research project  PI20/01715. This work was also supported by the  Regional Ministry of Education of Andalucia  through the research project  P20_00405. CAL holds a " Rio Hortega " contract ( CM21/00262 ). ATM held a " Rio Hortega " contract ( CM20/00160 ) and actually, a " Juan Rodes " contract ( JR22/00048 ); and  IEG holds a "Juan Rodes " contract ( JR19/00029 ), all granted by  ISCIII. This work was also supported by  ISCIII  (grants co-funded by the  European Regional Development Fund)  through its program  Redes de Investigacion Cooperativa Orientadas al Resultado en Salud (RICORS): Enfermedades Inflamatorias  ( RD21/0002/0008 ).
Inferring the evolution of aerobic lifestyles on the bacterial tree To evaluate the potential of the GOE to provide a maximum age constraint on aerobic lineages, and so to calibrate the bacterial time tree, we first determined transitions to aerobic lifestyles in the species tree of Bacteria. To achieve this, we inferred a species tree of 1007 bacterial genomes representing most orders in the Genome Taxonomy Database (  (Parks et al. 2018) ; Figure  1 , Supplementary Material). To study the evolution of oxygen use in Bacteria, we retrieved experimental data on the ability of extant isolates to grow in the presence of oxygen from the BacDive database (aerobic or anaerobic; in what follows, we use "aerobe" to refer to an organism that can grow in the presence of oxygen, see discussion in Supplementary Material) for 3184 species covering 249 GTDB orders  (Reimer et al.
Acknowledgements We thank  Julia A. Palacios  for providing R scripts to compute the D2 distance for ranked trees. This work was supported by the  Gordon and Betty Moore Foundation  through grant  GBMF9741  to TAW, AS, and GJSz. AD, DS,  LLSz  DS and GJSz received funding from the  European Research Council  under the European Union's  Horizon 2020 research and innovation program  under Grant Agreement (grant agreement No. 714774 ,  GENECLOCKS ). AS has received funding from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme  (grant agreement No. 947317 ,  ASymbEL ), the  Moore-Simons Project  on the  Origin of the Eukaryotic Cell, Simons Foundation   735929LPI  (https://doi. org /10. 46714/735929LPI ), and a  Gordon and Betty Moore Foundation's Symbiosis in Aquatic Systems Initiative  ( GBMF9346 ).
2′-5′-oligoadenylate synthetase 1 (OAS1) is one of the four members of the OAS family (OAS1, OAS2, OAS3, and the catalytically inactive OASL). These proteins are type I IFN-inducible cytosolic proteins that produce 2′-5′-linked oligoadenylates (2-5A) upon binding to doublestranded RNA (dsRNA). The 2-5A, in turn, induce the dimerization and activation of the latent endoribonuclease RNase L, which degrades single-stranded RNA (ssRNA) of viral or human origin  (42, 43). No homozygous variants fulfilling these criteria were identified in any of the 1288 subjects with asymptomatic/mild SARS-CoV-2 infection (SARS-CoV-2infected controls) in the CHGE database (fig. S1A to C ). MIS-C patients therefore display significant enrichment (P = 0. 013) in homozygous pLOF variants of the OAS1 and RNASEL genes, suggesting that these loci are probably relevant to MIS-C pathogenesis.
1. 1 and v3. 1. 1, 28 variants in total) in our RNase L-mediated rRNA degradation assay (fig. S2 , F to H, and table  S1 ). In total, 13 OAS1, OAS2 or RNASEL variants were deleterious and present in the homozygous state in 18 individuals in the gnomAD database (Fig. 1 , J to L). The estimated cumulative frequency of homozygous carriers of LOF variants at the three loci was ~0. 00013 (95% CI: 7. 2 -20 × 10 -5 ) in the general population. The rarity of AR OAS-RNase L deficiencies in the general population is therefore consistent with that of MIS-C. Moreover, the enrichment in these deficiencies observed in MIS-C patients relative to the individuals included in gnomAD was highly significant (P = 2 × 10 -6 ). These findings suggest that AR deficiencies of OAS1, OAS2, and RNase L are genetic etiologies of MIS-C.
The expression pattern for the OAS-RNase L pathway implicates mononuclear phagocytes We studied the basal expression of OAS1, OAS2, OAS3, and RNASEL in cells from different tissues. Consistent with data from public databases  (44) , our in-house human cell RNA-seq and RT-qPCR data showed that myeloid blood cells had higher basal mRNA levels for the four genes than the tissueresident cells tested (Fig. 2, A  and B ). In all cell types studied, both type I and type II IFN treatments up-regulated the levels of mRNA for OAS1, OAS2, and OAS3, whereas the levels of RNASEL mRNA were not influenced by these IFNs (fig. S3A ). Previous studies reported a relationship between cell typedependent activation of the OAS-RNase L pathway and basal levels of expression in mice  (45, 46). MIS-C occurs 3 to 6 weeks after SARS-CoV-2 infection, but the virus and/or viral proteins may still be detectable in non-respiratory tissues, such as the intestine or heart, at disease onset in some patients  (32, 34, 37).
Myeloid cell responses were characterized by a distinct pro-inflammatory component, such as IL1B and CCL3, that was stronger in OAS-RNase L-deficient cells (Fig. 5D  and data S2). We then calculated pseudobulk estimates by cell type. Consistent with the single-cell observations, genes strongly up-regulated by SARS-CoV-2 in OAS-RNase L-deficient myeloid cells were enriched in type I and II IFN signature genes and TNF signature genes, whereas those strongly up-regulated in CD4 + T cells were enriched in type I IFN signature genes (Fig. 5E ). Thus, there is an exaggerated inflammatory response to intracellular dsRNA or extracellular SARS-CoV-2 stimulation in primary monocytes and other mononuclear phagocytes with deficiencies of the OAS-RNase L pathway cultured alone or with other PBMC populations.
Whole-exome sequencing data analysis We performed an enrichment analysis focusing on the three candidate genes in our cohort of 558 MIS-C patients and 1288 children and adults with asymptomatic or paucisymptomatic SARS-CoV-2 infection (controls). We considered variants that were predicted to be loss-of-function or missense, with a highest population minor allele frequency (MAF)<0. 01, not included in segmental duplication regions (gnomAD v2. 1. 1). We considered genes corresponding to the Gene Ontology term "response to virus" (GO:0009615), with a gene damage index (GDI) below 13. 83  (41) , corresponding to the 90% least damaged genes. We searched for all homozygous variants in MIS-C patients, SARS-CoV-2-infected controls, and the gno-mAD database. We compared the proportions of patients and controls carrying experimentally confirmed deleterious homozygous variants by means of a logistic regression model, accounting for the ethnic heterogeneity of the cohorts by including the first five principal components of the principal component analysis (PCA), and for data heterogeneity (WGS and WES with various kits and calling processes) by including the two first PCs of a PCA on individual sequence-quality parameters, as previously described  (9).
The PCA for ethnic heterogeneity was performed with PLINK (v1. 9) on WES and WGS data, with the 1000 Genomes (1kG) Project phase 3 public database as a reference, using >15,000 exonic variants with a minor allele frequency > 0. 01 and a call rate > 0. 99. The PCA for data heterogeneity was performed with the R FactoMineR package and the following individual sequence quality parameters calculated with bcftools stats: number of alleles, number of ALT alleles, number of heterozygous variants, Ts/Tv ratio, number of indels, mean depth of coverage, number of singletons and number of missing genotypes, We also compared the frequency of experimentally confirmed deleterious homozygous variants of the three genes between our MIS-C cohort and gnomAD, in Fisher's exact test.
Plasmids For overexpression studies in HEK293T cells, wild-type (WT) cDNAs for OAS1 and RNASEL in a pCMV6 backbone were purchased from Origene. For rRNA degradation assays, human OAS1 (GenBank accession no. BC071981. 1), OAS2 (Gen-Bank accession no. BC049215. 1), OAS3 (GenBank accession no. BC113746), and RNASEL (GenBank accession no. L10381. 1) cDNAs were inserted into p3X-FLAG-CMV-10 (Sigma) as previously described  (75, 88). Patient-specific variants or variants from the gnomAD database were generated by site-directed mutagenesis PCR with the Super Pfx DNA Polymerase (CWbio). For stable lentivirus-mediated transduction with ACE2 and RNASEL, cDNAs for WT and patientspecific ACE2 or RNASEL variants were inserted into pTRIP-SFFV-CD271-P2A, a modified pTRIP-SFFV-mtagBFP-2A (Addgene #102585) in which mtagBFP is replaced with CD271, with InFusion (Takara Bio), according to the manufacturer's instructions.
Cell-free system assays of OAS and RNase L activity Assays for OAS and RNase L activity were performed with a modified cell-free system assay based on HeLa M cells  (49, 50). The HeLa M cells were cultured in DMEM with 10% FBS and their identity was confirmed by the presence of short tandem repeat loci with a 94. 12% match to HeLa cells (ATCC CCL2, Genetica, Burlington, NC). We previously reported that HeLa M cells have no RNase L expression  (51). Cells were plated in 24-well dishes (6 × 10 4 cells per well) with empty vector (p3X-FLAG-CMV-10), or vector containing WT or mutant human OAS1 (GenBank accession no. BC071981. 1), OAS2 (GenBank accession no. BC049215. 1), OAS3 (GenBank accession no. BC113746), or RNASEL (GenBank accession no. L10381. 1) cDNAs. HeLa M cells were cotransfected with cDNAs in the presence of Lipofectamine 2000 for 20 hours.
SARS-CoV-2 infection The SARS-CoV-2 NYC isolate was obtained from the saliva of a deidentified patient on 28 July 2020. The sequence of the virus is publicly available (GenBank OM345241). The virus isolate was initially amplified in Caco-2 cells (passage 1, or P#1 stock). For the generation of P#2 and P#3 working stocks, Caco-2 cells were infected with the P#1 and P#2 viruses, respectively, at a multiplicity of infection (MOI) of 0. 05 plaqueforming units (PFU)/cell and incubated for 6 days and 7 days, respectively, at 37°C. The virus-containing supernatant was then harvested, clarified by centrifugation (3000g for 10 min), and filtered through a disposable vacuum filter system with 0. 22-μm pores. The P3 stock used in this study had a titer of 3. 4 × 10 6 PFU/ml determined on Vero E6 cells with a 1% methylcellulose overlay, as previously described  (72).
Detection of secreted cytokines in a multiplex bead assay The harvested supernatants of stimulated THP-1 cells, PBMCs, and other types of cells were prepared and used for the LEGENDplex multiplex bead assay (BioLegend), according to the manufacturer's instructions. Samples were analyzed by flow cytometry on an Attune NxT flow cytometer, according to the manufacturer's instructions. Data were analyzed with LEGENDplex Cloud-based Data Analysis Software.
Bulk RNA sequencing (RNA-seq) Total RNA was extracted from THP-1 cells or sorted bloodcell populations. Cells were left untreated or were stimulated with poly(I:C) in the presence of lipofectamine or infected with SARS-CoV-2. RNA was extracted with the Quick-RNA MicroPrep kit (Zymo Research) or the RNeasy Micro Kit (Qiagen) and treated with DNase I (Zymo Research and Qiagen) to remove residual genomic DNA. RNA-Seq libraries were prepared with the Illumina RiboZero TruSeq Stranded Total RNA Library Prep Kit (Illumina) and sequenced on the Illumina NovaSeq platform in the 100 nt, paired-end configuration. Each library was sequenced twice. The RNA-seq FASTQ files were first inspected with fastqc to ensure that the raw data were of high quality. The sequencing reads of each FASTQ file were then aligned with the GENCODE human reference genome GRCh37.
p13 with STAR aligner v2. 6 and the alignment quality of each BAM file was evaluated with RSeQC. Reads were quantified with feature-Counts v1. 6. 0 to generate gene-level feature counts from the read alignment, based on GENCODE GRCh37. p13 gene annotation. The gene-level feature counts were then normalized and log2-transformed with DESeq2, to obtain gene expression values for all genes and all samples. Differential gene expression analyses were conducted by contrasting the intracellular poly(I:C)-stimulated samples or the SARS-CoV-2-infected samples with the non-stimulated samples. For each gene expression analysis, we performed TMM normalization and gene-wise generalized linear model regression by edgeR, and the genes displaying significant differential expression were selected according to the following criteria: FDR ≤ 0.
The data were then analyzed as described in detail in the supplementary materials. We also performed scRNA-seq on cryopreserved PBMCs from P5 (RNase L-deficient, aged 4 years) sampled during the acute (9 days after MIS-C onset) and convalescent (~1 month after onset) phases, together with cells from one healthy adult and two pediatric controls. We compared the data obtained with a previously published dataset for patients with pediatric acute SARS-CoV-2 infection or MIS-C  (33). Clustering analysis showed lower levels of monocytes and type 1 and type 2 conventional dendritic cells (cDCs) in these patients and an expansion of the activated T cell population strongly expressing MKI67 (Fig. 5F  and fig. S8, A  and B ). Other subsets were largely unaffected. Pseudobulk differential expression analysis were performed at the single-cell level for monocytes, myeloid dendritic cells (mDCs), B lymphocytes, plasmacytoid dendritic cells (pDCs), and activated T cells.
Bulk RNA-seq was performed on sorted non-classical monocytes and pDCs to further confirm the scRNA-seq findings. We also quantitatively inferred cell-cell communications with CellChat (74) to identify the signal-outgoing and the signal-receiving cell subsets. The data generated during this study were analyzed in an integrative manner with historical controls from the laboratory (one pediatric and seven adult controls), publicly available control PBMC datasets downloaded from the 10X Genomics web portal (https://support. 10xgenomics. com/single-cell-geneexpression/datasets), and a previously published dataset for patients with acute SARS-CoV-2 infection and MIS-C (GEO accession: GSE167029), as described in detail in the supplementary materials. In addition, two other previously published sets of scRNA-seq data for pediatric healthy controls and children with acute SARS-CoV-2 infection or MIS-C (GSE166489; Zenodo DOI: https://doi.
Statistical analysis For experiments performed in vitro, quantitative data were obtained for cells carrying the different mutations and control cells, or cells treated with different stimuli, from at least three biological replicates. For each biological replicate, up to six technical replicates were performed and averaged for downstream analysis. Cytokine determinations were logtransformed after subtracting the limit of detection for the experiment concerned. Mean quantitative values were compared between cells carrying the various mutations and control cells or cells treated with different stimuli in unequalvariance t tests. Where relevant, statistical test results are indicated in the corresponding figures. ns: not significant, *P < 0. 05, **P < 0. 01, ***P < 0. 001, ****P < 0. 0001. Table  1.
ACKNOWLEDGMENTS We thank the patients and their families for participating in our research. We thank all members of both branches of the  Laboratory of Human Genetics of Infectious Diseases  for discussions and technical and administrative support. We thank  A. W. Ashbrook  for managing the  Rice laboratory BSL3 facility. We thank the  Memorial Sloan Kettering Cancer Center  for help isolating and sequencing the NY SARS-CoV-2 isolate. We thank  R. Padgett  and  G. Stark  at the  Cleveland Clinic  for discussions. We also thank  A. Codina  and  C. Jou  from the  Biobanc de l'Hospital Infantil Sant Joan de Déu per a la Investigació , which is integrated into the  Spanish Biobank Network of ISCIII , for sample and data procurement. Funding: The  Laboratory of Human Genetics of Infectious Diseases  is supported by the  Howard Hughes Medical Institute , the  Rockefeller University , the  St.
Giles Foundation , the  National Institutes of Health (NIH)  ( R01AI088364  and  R21AI160576 ), the  National Center for Advancing Translational Sciences (NCATS) ,  NIH Clinical and Translational Science Award (CTSA) program  ( UL1TR001866 ), the  Yale Center for Mendelian Genomics  and the  GSP Coordinating Center  funded by the  National Human Genome Research Institute (NHGRI)  ( UM1HG006504  and  U24HG008956 ), the  Yale High-Performance Computing Center  ( S10OD018521 ), the  Fisher Center for Alzheimer's Research Foundation , the  Meyer Foundation , the  JBP Foundation , the  Research Agency (ANR)  under the  "Investments for the Future" program  ( ANR-10-IAHU-01 ), the  Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence  ( ANR-10-LABX-62-IBEID ), the  French Foundation for Medical Research (FRM)  ( EQU201903007798 ) , the  ANR GenMISC  ( ANR-21-COVR-039 ), the  ANRS -COV05, ANR GENVIR  ( ANR-20-CE93-003 ) and  ANR AABIFNCOV  ( ANR-20-CO11-0001 ) projects, the  ANR-RHU program  ( ANR-21-RHUS-08 ), the  European Union 's  Horizon 2020 research and innovation program  under grant agreement No.
824110  ( EASI-genomics ), the  HORIZON-HLTH-2021-DISEASE-04 program  under grant agreement  01057100  ( UNDINE) , the  ANR-RHU Program   ANR-21-RHUS-08  (COVIFERON), the  Square Foundation, Grandir -Fonds de solidarité pour l'enfance , the  Fondation du Souffle , the  SCOR Corporate Foundation for Science , the  French Ministry of Higher Education, Research, and Innovation  ( MESRI-COVID-19 ),  Institut National de la Santé et de la Recherche Médicale (INSERM)  and  Paris Cité University. We acknowledge support from the  National Institute of Allergy and Infectious Diseases (NIAID)  of the  National Institutes of Health  under award  R01AI104887  to R. H. S. and S. R. W. The  Laboratory of Human Evolutionary Genetics (Institut Pasteur)  is supported by the  Institut Pasteur , the  Collège de France , the  French Government 's  Investissement d'Avenir program ,  Laboratoires d'Excellence "Integrative Biology of Emerging Infectious Diseases"  ( ANR-10-LABX-62-IBEID ) and " Milieu Intérieur " ( ANR-10-LABX-69-01 ), the  Fondation de France  (no.
00106080 ), the  Fondation pour la Recherche Médicale  (Equipe FRM DEQ20180339214 team), and the  ANR   COVID-19-POPCELL  ( ANR-21-CO14-0003-01 ). A. Puj. is supported by the  ACCI20-759 CIBERER , the EasiGenomics  H2020  Marató  TV3 COVID 2021-31-33 , the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the  Horizon 2020 program  under grant no. 824110  (EasiGenomics grant no. COVID-19/PID12342 ), and the  CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the  Instituto de Salud Carlos III  ( COV20_01333  and  COV20_01334 ), the  Spanish Ministry of Science and Innovation  ( RTC-2017-6471-1 ;  AEI/FEDER, UE) ,  Fundación MAPFRE Guanarteme  ( OA21/131 ), and  Cabildo Insular de Tenerife  ( CGIEU0000219140  and "Apuestas científicas del ITER para colaborar en la lucha contra la  COVID-19 ").
The CoV-Contact Cohort was funded by the  French Ministry of Health  and the  European Commission  ( RECOVER  project). Our studies are also funded by the  Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr ,  65269705 ), and the  ANID   COVID0999  funding in Chile. G. N. and A. N. are supported by  Regione Lazio  (Research Group Projects 2020) No. A0375-2020-36663 ,  GecoBiomark. A. M. P, M. L. D. and J. P. T are supported by the  Inmungen-CoV2  project of  CSIC. This work was supported in part by the  Intramural Research Program  of the NIAID,  NIH. The research work of A. M. P, M. L. D, and J. M. P. T. was funded by the  European Commission -NextGenerationEU  ( Regulation EU 2020/2094 ), through  CSIC's Global Health Platform (PTI Salud Global).