dataesr/scientific-paragraphs-categorization huggingface dataset:
Relative label-free quantification of the proteins was conducted into Max-Quant using the MaxLFQ algorithm  56  with default parameters. Analysis of the identified proteins was performed using Perseus software (http://maxquant. net/perseus/) (version 1. 6. 12. 0). The file containing the information from the identification (proteinGroup. txt) was used. Briefly, the LFQ intensity of each sample were downloaded in Perseus and the data matrix was filtered by removing the potential contaminants, reverse and only identified by site. The LFQ intensity was logarithmized (log2[x]). Categorical annotation of the rows was used to define the different group. Venn diagram and principal component analysis (PCA) were done to compare the protein content of each sample. Statistical multiple-sample tests were performed using ANOVA with a p value of 1%.
Normalization was achieved using a Z-score with matrix access by rows. Only proteins that were significant by ANOVA were used. The hierarchical clustering and profile plot of only the statistically significant proteins were all performed and visualized by Perseus. Each protein cluster were selected and extracted for biological analysis. Functional annotation and characterization of the identified proteins were performed using FunRich software (version 3) and STRING (version 9. 1, http://stringdb. org). 57 Pearson's correlation coefficient and matrix representation were generated in R software using corrplot package. Gene Set Enrichment Analysis (GSEA) and Cytoscape software (version 3. 6. 1) were used for the biological process analysis of the clusters selected from the heatmap.
Subnetwork Enrichment Pathway Analyses and statistical Testing The Elsevier's Pathway Studio version 10. 0 (Ariadne Genomics/Elsevier) was used to deduce relationships among differentially expressed proteomics protein candidates using the Ariadne ResNet database. 58, 59 ''Subnetwork Enrichment Analysis'' (SNEA) algorithm was selected to extract statistically significant altered biological and functional pathways pertaining to each identified set of protein hits among the different groups. SNEA utilizes Fisher's statistical test set to determine if there are nonrandom associations between two categorical variables organized by specific relationships. Integrated Venn diagram analysis was performed using ''the InteractiVenn'': a web-based tool for the analysis of complex datasets. 60.
Mutation identification Proteins identification was also performed using the mutation-specific database. 32 XMan v2 database contains 2 539 031 mutated peptide sequences from 17 599 Homo sapiens proteins (2 377 103 are missense and 161 928 are nonsense mutations). The interrogation was performed by Proteome Discoverer 2. 3 software and Sequest HT package, using an iterative method. The precursor mass tolerance was set to 15 ppm and the fragment mass tolerance was set to 0. 02 Da. For high confidence result, the false discovery rate (FDR) values were specified to 1%. A filter with a minimum Xcorr of 2 was applied. The generated result file was filtered using a Python script to remove unmutated peptides. All mutations were then manually checked based on MSMS spectra profile.
) established a positive correlation between grades when the datasets are taken individually. Comparison of sentinel nodes and EC grades points out a positive correlation between grade I of both tissues. Using correlation matrices (Figure 5E), we found that PTMA (prothymosin alpha), ACTL6A, SHMT2, RBM25, and RBM4 were detected in grade I, II, and III sentinel nodes as well as in grade I, II, and III of EC. SUB1 and ETHE1 are expressed in grade II and III SLNs and grade II and III EC. DCD is present in grade I and II SLNs and grade I and II EC. YBX2, NOTUM, and RANDBP1 are found specifically in grade III SLNs and grade III EC. NUP210 is specific to grade II SLNs and grade II EC. PADI4, MUC5B, GOLM1, MNDA, CHI3L1, PTX3, SP100, MMP8, AZU1, and SLC9A3R2 are specific to grade I SLNs and grade I EC.
Patients and controls individuals We performed an observational study in which we determined CR1/E density and the levels of C3b/C3bi and C4d deposits on E in 52 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims, France. The number of longitudinal samples from a given individual ranged from one to five, leading to 114 samples from 52 patients, 32 of the patients having been tested more than once (supplemental Fig. 1 ). The first determination of CR1/E, or the lowest CR1/E level reached during longitudinal follow-up CR1/E determination for a given patient, were used to perform comparisons to different clinical or biological parameters from which the lower or the higher recorded value were considered. (Lowest SaO2% or Highest D-Dimer value). Data from historical cohorts of healthy volunteers, 400 blood donors under 60 years and 98 healthy individuals above 80, were used as CR1/E control populations.
Data analysis Statistical analyses were performed using BiostaTGV software http://biostatgv. sentiweb. fr/ (Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France), Calcstat software http://www. info. univ-angers. fr/~gh/wstat/calcstat. htm, G. Hunaut, Angers University Angers France; GraphPad Instat (GraphPad Software, San Diego California USA), and Origin software (OriginLab, Northampton, Massachusetts, USA). When Student's t-test was used, the normal distribution of the tested population was checked. Non parametric Wilcoxon or Spearman tests were used for too small or non-normal sub-populations.
Values for E CR1 density from the elderly controls (Mean = 606 SD = 248 N = 98) were similar to those for blood donors under 65 (Mean = 592 SD = 287 N = 400) (Fig. 1 ). Some longitudinal data was available for 32 patients. We analyzed the dynamics of CR1/E density over the course of the disease, using the onset of symptoms as a proxy for the onset of the disease. Although most patients exhibited low CR1/E values early in the disease, a clear progressive decrease of CR1/E occurred around day 10 of symptoms in some individuals, whereas on follow-up 2-3 weeks later, during recovery, some individuals displayed a return to values in the normal range (Supplemental Fig. 1 ). Interestingly, 6 patients received blood transfusions before testing that didn't dramatically increase CR1/E in active disease, even after one individual received 8 E packs.
We also measured the reactivity of plasma against AMA-1 construct, representing AMA-1 extracellular part, expressed in the same system  29  , as this protein might reflect the level of exposure of children to P. falciparum malaria, and analyzed data similarly by stratification to high and low anti-AMA IgG levels. Samples from children with CM at admission (day 0) were tested in these experiments. Normal distribution in all sets of data was tested by three tests (D' Agostino & Pearson, Shapiro-Wilk, and Kolmogorov-Smirnov) using GraphPad Prizm software. Statistical significance (P < 0. 05) was determined by t-tests for normally distributed data and by Mann-Whitney tests for non-parametric distributions.
Acknowledgements We would like to thank all children and their parents for participating in this study. We are grateful to the pediatricians and nurses in CHUMEL, CNHU-HKM, and  CHU of Suru-Léré  for their participation in sample collection and in facilitating our field work. This work was supported by  UMR261  is part of the  Laboratory of Excellence GR-Ex , reference  ANR-11-LABX-0051 , funded by the program " Investissements d'avenir " of the  French National Research Agency , reference  ANR-11-IDEX-0005-02  and by  NIH  grant  R01AI092120  to AVO. The funders had no role in study design, data collection and analysis, decision to publish or preparation of manuscript.
Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. Methods Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. Results Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.
METHODS The DORIS Task Force was first convened in 2015 and consisted of patient representatives and specialists in rheumatology, nephrology, dermatology and clinical immunology. Following the 2016 publication of the framework for such a definition, the full task force was reconvened in 2018 and again in 2020. The steering committee met on several more occasions, and further work by the task force was done through telephone and web conferences and by email. The task force deliberations were based on systematic literature reviews (SLRs) and specific topical analyses. Data from individual cohorts and registries were reviewed in detail to provide additional information. A typical meeting would begin with such presentations, following which the main topics for further discussion were determined.
Epidemiology and outcomes Furthermore, remission was independently associated with a decreased risk for subsequent hospitalisation (HR 0. 46). 9 In Almenara, a cohort of more than 300 mostly mestizo patients from Peru, the same associations were found using the LupusQoL. 10 Data from Almenara also showed that remission was independently associated with decreased risk of subsequent hospitalisation (HR 0. 45),  11  and that remission (on-treatment) prevented damage accrual (HR 0. 59). 12 ► Data from the international multiethnic LUMINA cohort were reviewed. The LUMINA cohort includes 640 patients of African American and Hispanic (Puerto Rico) ancestry from three US centres. In LUMINA, disease activity at baseline and a higher dose of prednisone prevented patients from achieving remission or low disease activity (LDA); and having health insurance increased the probability of achieving remission/LDA.
Voting session The task force achieved consensus on five general recommendations (in addition to those published previously), as well as on a final definition of remission (box 1). These statements were carried by a wide margin (>90% agreed). Table  2  shows these statements, which were generated as the result of substantial reviews of the literature and data from individual registries and clinical trial data sets. The first recommendation dealt with the inclusion of serology (anti-dsDNA, complement) in the DORIS definition of remission on-treatment. Because the preponderance of the data suggests that this does not meaningfully alter the construct validity of a definition of remission, it is not recommended to include it. The second recommendation deals with the question of duration and the task force agreed that, while the goal of treatment is sustained remission, a definition of remission should be able to be met at any point in time, so that duration should not be included in the definition.
DISCUSSION The DORIS Task Force on definition of remission in SLE, an ad hoc task force comprised of patient representatives and medical specialists with varying backgrounds, undertook a multiyear process in order to arrive at a definition of remission in SLE for use in patient care, education and research including clinical trials. This initiative resulted in a framework published several years ago and, in the current report, the final recommendations including the proposal for the 2021 DORIS definition of remission in SLE. Multiple cohort studies done in recent years support several aspects of the validity of the proposed definition of remission. Thus, the data demonstrating that various DORIS remissions are associated with lower PGA (Amsterdam cohort), as well as with better concurrent HR-QoL (Amsterdam, LUMINA, Almenara), support the face validity of DORIS remissions.
Similarly, the association of DORIS remission with less damage (GLADEL, LUMINA, Hopkins, Padua, Almenara) and fewer hospital admissions (GLADEL, Almenara) supports the construct (or predictive) validity of this definition. The effort of this task force was evidence based to the greatest possible degree, with SLRs and analyses of suitable data sets being the starting points for all deliberations. Nonetheless, practical considerations also applied. Thus, it was found that definitions of remission that would require the patient to be on no treatment (other than, possibly, antimalarials) would be achieved too rarely for such a definition to be meaningful in analyses, and the concern was raised that in some settings, overly zealous efforts to achieve remission off-treatment could lead to the withdrawal of needed therapies with negative consequences for the patient.
Moreover, a definition of remission that is agnostic to duration allows future studies examining effects of duration. For example, studies can be done to determine the minimum remission time capable of achieving outcomes such as improved HR-QoL or reduced damage. Thus, the DORIS Task Force feels that the current definition represents the best possible balance between scientific rigour and practical considerations. Major discussions took place over the issue of whether to 'allow' any glucocorticoids in the definition, especially since some studies suggest how even low doses of glucocorticoids have (long-term) risks (of course, the data are not fully conclusive, since residual bias in these studies cannot be excluded completely). For this very reason, many task force members expressed the same view that a remission without glucocorticoids is preferable for the patient.
Acknowledgements The following individuals provided valuable input during the DORIS process:  Ellen Ginzler ,  Dan Goldman ,  Winfried Graninger ,  Veronique Le Guern ,  Liesbeth Hak ,  Munther Khamashta ,  Francinne Machado Ribeiro ,  Irmgard Neumann ,  Ole Rekvig ,  Jozef Rovensky ,  Francesca Saccon ,  Murray Urowitz  and  Asad Zoma. Contributors All authors were participants in the live DORIS Task Force meetings and the electronic deliberations and voting. Thus, they were all involved in the conceptualisation of the work reported here, and they all participated in the generation of the data. All authors critically reviewed the manuscript before final submission, and all authors gave their approval for publication. RFvV is the guarantor. Funding The  DORIS Initiative  was supported by unrestricted educational grants from  Glaxo SmithKline  and  UCB Pharma.
Measures G*Power software was used for each statistical analysis in the study. We used the same protocol as Prigitano and colleagues  [20] , based on the original WHO questionnaire while including some modifications to the measures they proposed and adding a supplementary scale (see Supplementary Materials, Figures  S1  and S2 ). The survey was divided on 3 parts: the first part dealing with uses and general knowledge was constructed of 7 closed questions (questions #1 to #7). In a second part, participants were asked to answer one scale in a counterbalanced order composed of 20 items (question #8). These items are based on the 19 items proposed by Prigitano and colleagues (and one additional item we included in this scale), but instead of true/false answers, participants answered on 6-point Likert scales (from 1 = "not agree at all" to 6 = "completely agree").
The only published study concerning neonatal microglia reported a role for mGlu5 receptors in the control of neuroinflammation following excitotoxic insult  [7]. Recent studies have shown that mGlu3 receptors boost mGlu5 receptor signaling in brain tissue and cultured astrocytes and that mGlu3 activation is required for a full mGlu5 receptor response to agonist activation  [29] [30] [31]. We therefore investigated whether mGlu3 receptors, encoded by Grm3 gene, play a role in the modulation of brain inflammation, in particular in microglial cell reactivity. We investigated Grm3 gene expression in vivo and in primary microglial cells sorted from neonatal rats. Bioinformatics analysis of a large microarray dataset shows Grm3 to be a major hub in the control of inflammation in resting and activated microglia.
RNA purification, cDNA synthesis, and real-time qPCR Samples were immediately snap frozen after collection. Total RNA from the cortex was extracted using Nucleazol reagent and the NucleoSpin RNA Set for NucleoZol (Macherey-Nagel, Hoerdt, France). Microglial RNA was isolated using NucleoSpin RNA Plus XS (Macherey-Nagel). RNA quantity and quality were determined using the NanodropTM apparatus (Thermofisher Scientific, Waltham, MA, USA). Reverse transcription was performed using the IscriptTM cDNA synthesis kit (Bio-Rad, Marnes-la-Coquette, France). Primers were designed using Primer3Plus software, and sequences are available on request. RT-qPCR was performed in triplicate as reported in  [34]  using the Ribosomal protein L13 (Rpl13) as the reference gene.
Proteins were stained using Ponceau S solution (Sigma-Aldrich) and digital images acquired. The optical density of each well was measured using NIH ImageJ medical imaging software. Blots were incubated in a blocking solution containing Tris-buffered saline (TBS), 0. 1% Tween-20 (Sigma-Aldrich), and 5% non-fat milk (Bio-Rad) for 1 h at room temperature. Blots were then incubated overnight with rabbit anti-mGlu3 receptor (1:600; AGC-012, Alomone Labs, Jerusalem, Israël) in blocking solution at 4 °C. After incubation with the primary antibody, the blots were incubated with horseradish peroxidase-conjugated goat anti-rabbit (1:2000; 0545, Sigma-Aldrich) for 1 h at room temperature. Bands were visualized by enhanced chemiluminescence using Clarity Max ECL (Bio-Rad). Digital images were acquired and the optical density of each band measured as described above.
Statistical analysis Statistical analysis of all data was performed using GraphPad PRISM version 8. 0 (San Diego, CA, USA). Student's t test was performed for two-group comparisons. A one-or two-way ANOVA, followed by the Newman-Keuls post hoc multiple comparison tests, was performed for comparison of more than two groups. A Pearson correlation test was used to analyze relationship between Grm3 and inflammatory cytokines' mRNA expression in siRNA experiment. A multiple t test was performed to analyzed microarray data. Significance was set at p < 0. 05 for all tests. Number of samples, statistics, and p values are reported in Additional Table  1. Morphological data and Iba1 + cell density were analyzed by a person who was blind to experimental conditions. Pups from 2-3 litters were used in each experiment.
Pharmacological blockade of mGlu3 receptors increased the expression of all pro-inflammatory markers in primary microglia from P4 rat pups under basal conditions and in response to IL-1β + IFNγ (Fig. 4c ). LY 2389575 also induced an increase in Mrc1 levels under basal conditions and a significant reduction of Arg1 expression in response to IL-1β + IFNγ (Fig. 4d ). Similar effects were produced by LY ) and the cell area, cell perimeter, and cell circularity were assessed in b. Data (mean ± SEM). Two-way ANOVA followed by the Newman-Keuls multiple comparison test; *p < 0. 05, **p < 0. 01, ***p < 0. 001 effect of LY379268 + Ro 64-5229; $ p < 0. 05, $$ p < 0. 01, $$$ p < 0. 001 effect of IL-1β + IFNγ; # p < 0. 05, ## p < 0. 01, ### p < 0. 001, #### p < 0. 0001 effect of LPD/IL-1β. c, d mRNA expression of pro-inflammatory (c) and anti-inflammatory/immune-regulatory (d) markers under basal and pro-inflammatory conditions ± LY 379268 (1 μM) + Ro 64-5229 (25 μM).
The more limited downregulation of mGlu3 levels in the entire cerebral cortex may reflect the presence of the mGlu3 receptor in neurons and astrocytes  [14] , for which the impact of LPD/IL-1β on receptor expression is yet to be determined. A peak of microglial Grm3 gene expression was observed at P4-7 and a subsequent decline through to P20 in rats, but other single-cell RNAseq datasets in mice (http://www. microgliasinglecell. com) suggest that Grm3 microglial expression was similar at P4 and P30 and substantially increased at P100  [39]. These apparent discrepancies based on transcriptomic analyses between rats and mice may be explained by species specificity, difference in various sequencing depths, and the limitation of our experiments to the P20 developmental stage. Another explanation may originate from our microglia sorting method (MACS) with respect to the FACS used in the RNAseq experiments in mice.
Two-way ANOVA followed by the Newman-Keuls multiple comparison; $ p < 0. 05, $$ p < 0. 01 effect of IL-1β + INFγ; # p < 0. 05, ## p < 0. 01 effect of Grm3 -/-. c, d Iba1 + cells within Cingular white matter of P4 WT and Grm3 -/-mice under basal conditions and after IL-1β injections. Representative photomicrographs at × 40 magnification are shown in c (scale bar = 25 μm). The cell area, cell perimeter, and cell circularity were assessed in d. Data (mean ± SEM). Twoway ANOVA followed by the Newman-Keuls multiple comparison; $$ p < 0. 01, $$$ p < 0. 001 effect of IL-1β + INFγ; # p < 0. 05, ## p < 0. 01, ### p < 0. 001 effect of Grm3 -/-. e, f mRNA expression of pro-inflammatory (e) and anti-inflammatory/immune-regulatory (f) markers in Prefrontal/Cingular cortex isolated from P4 WT and Grm3 -/-mice under basal conditions and after IL-1β injections.
The use of CTV distribution as a parameter of global protein repartition in telophase together with the acquisition of an important number of cell divisions strengthens our analysis. In addition, we investigated lytic granule repartition in dividing CD8 + T cells by 3D confocal laser scanning microscopy and 4D live cell imaging. These techniques allowed visualization of lytic granule repartition in telophase with a high time/space resolution and strengthened imaging flow cytometry data by providing unambiguous visualization of lytic granule partitioning. Our results demonstrate that the uneven lytic machinery distribution is not related to ACD. In mouse T lymphocytes, ACD has been reported as a mechanism contributing to the generation of effector/memory daughter cells following division of an individual naive T cell in response to polarizing cues  (Arsenio et al.
Before FACS analysis, 0. 25µg 7-Aminoactinomycin D (7-AAD; BD Biosciences) and FITC conjugated anti-CD8 antibody were added to each sample in order to measure the percentage of dead target cells. For the CD107a exposure and CD8 internalization assay, sorted CTL were incubated with target cells at 0. 5:1 E/T ratio for 4 hours. Cells were stained with PE-cy7 conjugated anti-CD107a antibody and FITC conjugated anti-CD8 antibody for 30 min in FACS-buffer (1% human serum, 1% Foetal Calf Serum in PBS), washed, acquired on a Fortessa flow cytometer (BD Biosciences) and analysed by using FlowJo software (TreeStar).
Statistical methods Paired Student's t-test, was performed to determine the statistical significance of differences between the groups (GraphPad Prism software version 5). Chi-square of independence test was performed to determine the independence between the level of expression of a given marker and the capacity of a cell in telophase to asymmetrically distribute this marker (Python software version 3. 5). Kolmogorov-Smirnov goodness of fit test was performed to compare law between probability distribution of a marker of interest in cells in G1 (Python software version 3. 5). Chi-square of homogeneity test was performed (in addition Kolmogorov-Smirnov goodness of fit test) to determine where the probability distribution of a marker of interest varies (Python software version 3. 5). In the independence Chi-square test, we compare the theoretical effective ( , ) to the observed effective ( , ).