dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical significance was considered at P ≤ 0. 05 and a tendency was considered at 0. 05 < P ≤ 0. 10. For bioinformatic analysis of the 16S sequencing data, the sorted reads were imported and processed using the Quantitative Insight into Microbial Ecology (QIIME2) package version 2021. 2  (Boylen et al. , 2019). First, low-quality reads (Phred score < 20) and short (<100 bp) reads were filtered out. This was followed by denoizing and merging using the plugin DADA2 to generate an amplicon sequence variant (ASV) feature table. Chimeric sequences and singleton ASV were excluded from further analyses. Alpha-diversity analyses were conducted with standard diversity metrics accessed via QIIME2, including Chao1, Shannon index, and Phylogenetic diversity (PD) index. A nonparametric ANOVA (Kruskal-Wallis test) was used to test differences in α-diversity among treatment groups and to calculate P-values.
Beta diversity was calculated based on the weighted UniFrac distances and nonmetric multidimensional scaling (NMDS) was applied to the resulting distance matrix. Analysis of similarity was used to calculate P-values and to test differences in β-diversity among the different days for significance. Statistical significance was declared at P ≤ 0. 05 and a tendency was considered at 0. 05 < P ≤ 0. 10. Lastly, to understand if the changes of lymphocyte populations in the colon during weaning were partially accounted for by changes in colon microbial diversity, we perform nonparametric Spearman's rank correlation analysis using the data from d 28 and 42. This analysis was used to test if the changes in the proportion of total γδ T cells, γδ T cell subsets, IgM + lymphocytes, and proportion of IgM + B cells expressing CD21 + and CD32 + from colon IEL were correlated with changes in the colon epimural microbial diversity in samples from d 28 and 42.
ACKNOWLEDGMENTS This study was supported by funding from  Lallemand Health Solutions (Mirabel, QC, Canada) , the  Saskatoon Colostrum Co. Ltd. (Saskatoon, SK, Canada) , and the  Natural Sciences and Engineering Research Council of Canada (Ottawa, ON, Canada). The authors gratefully acknowledge the staff of the  Ponsonby Research Station (University of Guelph, Guelph, ON, Canada ) for their assistance with the animal experiment, and  Jaeju Yu  for his assistance with laboratory analysis ( Department of Animal Biosciences, University of Guelph,   Guelph, ON, Canada ). The authors have not stated any conflicts of interest.
We performed each staining on a single slide (3 sections for each staining) from the same level of the aortic root for all experimental and control mice. Computer-assisted analysis (Image-J) was used to determine lesion size and areas or cell counts for specific cell types. All slides for each experiment were analyzed by the same blinded observer to minimize variations. All measurements were performed by manual selection of stained pixel thresholds and presented as total or percent positive (stained) area relative to the entire intimal area. CD4 + T cells were counted, and the data are presented as the number of T cells per total number of cells in atherosclerotic plaques. Whole aortas were used in an en face (https://www. ebi. ac. uk/arrayexpress/experiments/E-MTAB-11677/). The alignment and QC were processed using the nextflow (version 21.
05. 0 edge 46 ) pipeline nf-core/rnaseq (version 3. 2, https://nf-co. re/rnaseq; 47 ) with the option "-aligner star_salmon" and Ensembl reference genome and annotation for mouse GRCm39. All data are freely available from https://github. com/CAD-BFX/Meri_Ziad. There are 55359 genes identified after next flow pipeline in total with Ensembl Gene ID annotation. These genes as input to perform the differential gene expression analysis using DESeq2 package (version 1. 34. 0 48 ) in R (4. 1. 2 (2021-11-01)  49  ). The design formula for DESeq2 analysis is ~Sex+Condition. After the DESeq2 analysis, 37,349 genes are removed because the missing p-adjusted values. The total number of genes for the rest of the analysis is down to 18,010. Further analysis to show the selected DEGs is presented by Heatmaps.
Heatmaps are generated using R package ComplexHeatmap (version 2. 10. 0 50 ). Fully DEGs and selected DEGs lists are in Supplementary Data 1 and available in GitHub https://github. com/CAD-BFX/Meri_Ziad The gene ontology analysis performed using the web interface Enrichr (https://maayanlab. cloud/Enrichr/) with 518 up regulated and 551 down regulated DEGs list, respectively. Selected GO pathways are plotted in Figure  3E. Quantitative real time polymerase chain reaction. For gene expression analysis, RNA from sorted MZB cells and splenic cells from fresh frozen OCT spleen sections were isolated using RNAeasy nano kit (Qiagen). RT-PCR was performed using QuantiTect Reverse transcription kit (Qiagen) or SMART-Seq v4 (Takara Bio) depending on the yield of mRNA. qRT-PCR was performed with Power SYBR Green Master Mix (Thermo Fisher).
ACKNOWLEDGEMENTS We acknowledge  Ana Petrunkina ,  Natalia Savynkh  and  Nika Romashova  in the Phenotyping Hub of the  Department of Medicine (University of Cambridge ) for their help in flow cytometry and sorting. We acknowledge measurements of lipids, BAFF and IL5 in blood by  Keith Burling  and  Peter Baker  and the  Core Biochemical Assay Laboratory (CBAL). This work was supported by the  British Heart Foundation (BHF)   Intermediate Basic Science Fellowship  ( FS/20/23/34784 ) to MN and the  BHF Project Grant  ( PG/17/73/33251 ) to MN and ZM. ZM is supported through a  BHF Chair of Cardiovascular Medicine  ( G101517 ). This work was also supported by  Leducq Foundation  to ZM, CM and CB ( G107743 ),  RITA-MI  project funded through  H2020  to ZM ( G106938 ). The RIPPLE study was supported by from the  Wellcome Trust  [211100/Z/18/Z] and the  British Heart Foundation  [ FS/CRTF/20/24035 ] to JMT.
With an overall median follow up time after transplantation of 18m (range 4-42m) by 05/2023, all but three patients are alive (n=23/26, 88%). All three deaths were from the non-NBS group. Two patients had pre-existing viral infections, dying at 8 and 9m after thymus transplantation without establishment of thymopoiesis. The third patient had treatment-refractory autoimmune haemolytic anaemia and died 3 years post-transplantation from complications of immunosuppressive therapy. Regular immunological monitoring was performed in all transplanted patients. Assessment of thymic output included measurement of CD4 + CD27 + CD45RA + naïve (nCD4 + ) T-cells. At 6 ±1 months posttransplantation (data available in 22 patients), patients treated at <4 months of age had higher absolute counts and proportions of nCD4 + T-cells (median: 100 cells/μL, range: 50-1680 cells/μL; median: 37.
Gene synthesis The full length EHV-1 gB, gD, gH and gL gene sequences (ORF 33, 72, 39 and 62 respectively) were obtained from an EHV-1 strain isolated from organs of an aborted horse foetus during a significant EHV-1 outbreak in Normandy (France) in 2010  (Sutton et al. , 2019). The strain nomenclature is EHV-1 2010. 203 (year and the sample ID) and belongs to the Multi Locus Sequence Typing (MLST) group 10. The GP gene sequences were aligned with the respective homologues in the references EHV-1 strains: Ab4 (GenBank accession number: AY665713. 1)  (Telford et al. , 1992)  and strain V592 (GenBank accession number: AY464052. 1)  (Tearle et al. , 2003)  to verify the correct ORF length. All GP genes (plus upstream Kozak sequence and terminal restriction sites) were synthesised by GeneArt™ (Thermo Scientific™, Thermo Fisher Scientific) cloned into their in-house pMX plasmid vectors, with the exception of gC (ORF 16) which was synthesized and supplied as a 'gene string' linear DNA fragment.
The EHV-1 gC sequence was obtained from EHV-1 strain Suffolk/87/2009 (GenBank accession number: KU206443. 1), also belonging to the MLST group 10  (Bryant et al. , 2018). 2. 3. Plasmid preparation gB, gD, gH and gL genes were subcloned from pMX into the pCAGGS expression plasmid  (Niwa et al. , 1991)  previously used to produce functional pseudotypes representing a number of virus families  (Di Genova et al. , 2021; Kemenesi et al. , 2022; King et al. , 2016). The gB gene was subcloned via a blunt end strategy with XbaI (filled using Klenow fragment polymerase) and XhoI restriction enzymes and T4 ligase. The gD, gH and gL genes were cloned using KpnI and XhoI and gC gene via EcoRI and BglII restriction enzymes. All enzymes from Thermo Scientific™, Thermo Fisher Scientific. All plasmids were purified using Monarch® Plasmid Miniprep Kit (New England Biolabs) with concentration and purity determined using a Nanodrop™ 2000 Spectrophotometer (Thermo Scientific™, Thermo Fisher Scientific)).
An equine influenza (EIV) PV bearing both the haemagglutinin (HA) and neuraminidase (NA) surface GPs from the Florida clade 2 EIV strain A/equine/Richmond/1/07 (H3N8) (GenBank accession number: KF559336. 1) was produced as previously reported and utilised as a positive control for the titration procedure  (Kinsley et al. , 2020; Scott et al. , 2016). Plates were incubated for 48h at 37℃ at 5% CO 2 before reading. For fluorescence evaluation, green fluorescent protein (GFP) expressing cells were manually counted under a fluorescent microscope (Nikon, model: Eclipse TS100). On the other hand, Bright-Glo™ luciferase assay system (BG; Promega) was employed to measure the luminescence (in relative luminescence units; RLU per mL of supernatant) of PV supernatant. Briefly, BG was mixed with phosphate-buffered saline (PBS; PAN Biotech) in a 50:50 ratio and 25 µL/well added to the 96-well plate to wells where medium had been removed.
After 5 minutes incubation, the plate was read on a GloMax® Navigator Microplate Luminometer (Promega). 2. 6. Serum samples A panel of horse serum was collected as part of an experimental EHV-1 challenge study previously described by  Thieulent et al. , (2022). This archived serum panel was tested for EHV-1 specific neutralising antibodies in the current study. The panel consisted of a total of 52 samples from four 10 month-old male Welsh Mountain ponies (A, B, C and D), which had been raised in a dedicated specific pathogen free facility since birth and were experimentally infected by individual nebulisation with the C 2254 strain of EHV-1 (GenBank accession number: MT968035. 1)  (Sutton et al. , 2020; Thieulent et al. , 2022). Sample collection occurred five days before infection (A 0 , B 0 , C 0 , D 0 ) and then daily from day 8 to day 18 (corresponding to sample A 8 to A 18 , B 8 to B 18 , C 8 to C 18 , D 8 to D 18 ) period during which a seroconversion could be recorded.
5, Labconco, model: 7670560) using the method described in  (Mather et al. , 2014). Next, the lyophilised pellets were stored for various time periods at different temperatures: one week or four weeks at +37℃, RT with or without surrounding ice blocks (in polystyrene boxes), +4℃, -20℃ and -80℃. Lyophilised PVs were reconstituted in complete media and titrated to assess the recovery percentage. 2. 9. Statistical tools Raw data files produced by the luminometer were analysed using Microsoft® Excel™ 365 software (Microsoft® Windows). Column bar graphs and the non-linear regression curve fits were produced using GraphPad Prism®. Statistical analysis was performed for comparison using a Student's t-test (p<0. 005).
Image processing For the TEM Titan Krios dataset, movie drift correction was performed using Relion's Motioncor implementation, with 7x5 patch, using all movie frames  (Zheng et al. , 2017). All additional initial image processing steps were performed in cryoSPARC v3. 3  (Punjani et al. , 2017). CTF parameters were determined using "Patch CTF estimation", realigned micrographs were then manually inspected and low-quality images were manually discarded. To obtain an initial 3D reconstruction of FluPol Zhejiang-H7N9 4M, particles were automatically picked on few hundreds micrographs using a circular blob with a diameter ranging from 100 to 140 Å. Particles were extracted using a box size of 360 x 360 pixels 2 , 2D classified and subjected to an "ab-initio reconstruction" job. The best initial model was further used to prepare 2D templates.
Post-processing was performed in Relion using an automatically or manually determined B-factor. For each final map, reported global resolution is based on the FSC 0. 143 cut-off criteria. Local resolution variations were estimated in Relion. Detailed image processing information is shown in Fig. S7. For the TEM Glacios dataset, EER fractionation was set to 24, giving ~1e -/Å 2 per resulting fraction. Movie drift correction was performed using Relion's Motioncor implementation, with 5x5 patch  (Zheng et al. , 2017). All additional initial image processing steps were performed in cryoSPARC v4. 1  (Punjani et al. , 2017). CTF parameters were determined using "Patch CTF estimation", realigned micrographs were then manually inspected and low-quality images were manually discarded. To obtain an initial 3D reconstruction of FluPol Zhejiang-H7N9 PA K289A+C489R, particles were automatically picked on few hundreds micrographs using a circular blob with a diameter ranging from 100 to 140 Å.
Model building and refinement Using the FluPol Zhejiang-H7N9 elongation complex as starting point (PDB: 7QTL)  (Kouba et al. , 2023) , atomic models were constructed by iterative rounds of manual model building with COOT and real-space refinement using Phenix  (Afonine et al. , 2018). Validation was performed using Phenix. Model resolution according to the cryo-EM map was estimated at the 0. 5 FSC cutoff. Figures were generated using ChimeraX  (Goddard et al. , 2018).
Acknowledgments We thank  Ron Fouchier  ( Erasmus MC Department of Viroscience, Netherlands ),  George Brownlee  ( Oxford University ),  Bernard Delmas  ( INRAE, France ),  Robert-Jan Lebbink  ( Utrecht University, Netherlands ) and  Sandie Munier  ( Institut Pasteur, France ) for sharing plasmids and antibodies. We thank  Martin Pelosse  for support in using the Eukaryotic Expression Facility at  EMBL Grenoble ;  Aldo R. Camacho-Zarco  and  Martin Blackledge  for providing huANP32A truncated constructs proteins;  Daphne Walter  and  Vladimir Benes  from the  EMBL GeneCore facility  for the next generation sequencing data;  Wojtek Galej ,  Sarah Schneider  and  Romain Linares  for access to the Glacios at  EMBL Grenoble ;  Guy Schoehn  and  Eleftherios Zarkadas  for access to the Glacios at  IBS Grenoble ;  Aymeric Peuch  for support with using the joint EMBL-IBS computer clusters.
Funding sources This work was funded by the  ANR  grant  FluTranscript  ( ANR-18-CE18-0028 ), held jointly by SC and NN. TK was funded by the  ANR  grants Flutranscript  ANR-18-CE18-0028  and  ANR-10-LABX-62-IBEID. This work used the platforms at the  Grenoble Instruct-ERIC Center  (ISBG ; UMS 3518  CNRS CEA-UGA-EMBL ) with support from the  French Infrastructure for Integrated Structural Biology (FRISBI  ;  ANR-10-INSB-05-02 ) and  GRAL , a project of the  University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche)   CBH-EUR-GS  ( ANR-17-EURE-0003 ) within the  Grenoble Partnership for Structural Biology. The  IBS Electron Microscope  facility is supported by the  Auvergne Rhône-Alpes Region , the  Fonds Feder , the  Fondation pour la Recherche Médicale  and  GIS-IBiSA.
003 PDB ID 8PNQ 0. 005 EMDB ID Bond angles (°) EMD-17755 0. 475 EMD-17782 0. 499 EMD-17783 0. 465 Data collection Validation and processing MolProbity score 1. 53 1. 35 1. 40 Microscope Voltage (kV) All-atom clash score 4. 79 ThermoFisher Krios TEM 300 4. 32 3. 86 Camera Poor rotamers (%) Gatan K3 direct electron detector mounted on a Gatan Bioquantum LS/967 energy filter 2. 03 1. 24 2. 01 Magnification Ramachandran plot Nominal defocus range (µm) Favored (%) 97. 77 105000 -0. 8 / -2. 0 97. 70 98. 24 Electron exposure (e-/Å 2 ) Allowed (%) Outliers (%) 2. 23 0. 00 2. 24 40 0. 06 1. 76 0. 00 1304 Number of frames collected 40 (no. ) Number of frames processed 40 (no. ) Pixel size (Å) 0. 84 Initial micrographs (no. ) 6000 Final micrographs (no. ) 5883 Refinement Particles per class (no. ) 33395 260565 14878 Map resolution (Å), 0.
Selection of patients Between 2012 and 2019, 195 patients (178 adults, 6 adolescents, and 11 children 3-11 years old) with secondary HLH were prospectively recruited from 62 medical centers in a national study (funded by the French National Program of Clinical Research, 2010). The inclusion criteria were adapted from the HLH-2004 diagnostic criteria  32  and with the expertise of the French HLH Study Group, as recommended  33  (see Table  E1  in this article's Online Repository at www. jacionline. org). Informed consent was obtained from all study participants following the Declaration of Helsinki. The regional Ethics Committee of Paris (ID-RCB: 2009-AO00301-56) approved the study. The data collected included clinical and biological features of HLH, ADs, infectious trigger events, treatment, and outcomes (refractoriness to treatment [corticosteroids and etoposide] or relapse, intensive care unit [ICU] transfer, and death) at HLH onset and during a 1-year follow-up.
After the exclusion of intronic (n 5 138), UTR3 (n 5 5), UTR5 (n 5 2), and splicing (n 5 14) variants, as well as synonymous variants (n 5 53), a total of 59 nonsynonymous variants were retained for further analyses, all of them being missense and exonic. Finally, variants were subsequently selected if they met at least 2 of the following criteria: (1) the maximum minor allelic frequency in reference subpopulations is less than 0. 05 (ANNO-VAR PopFreqMax annotation), (2) CADD phred score is greater than or equal to 14. 399, and (3) PolyPhen-2 HVAR score is greater than or equal to 0. 429 according to the Mutational Significance Cutoff database thresholds  41.
DISCLOSURE STATEMENT This work was supported by grants from Programme Hospitalier de la Recherche Clinique Nationale 2010 of the French Ministry of Social Affairs and Health (clinicaltrials. gov no. NCT02113917) and Direction de la Recherche Clinique et de l'Innovation of Assistance Publique-Hôpitaux de Paris. It also received financial support from Laboratoire Francais du Sang. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
Scope: These European Society of Clinical Microbiology and Infectious Diseases guidelines are intended for clinicians involved in diagnosis and treatment of brain abscess in children and adults. Methods: Key questions were developed, and a systematic review was carried out of all studies published since 1 January 1996, using the search terms 'brain abscess' OR 'cerebral abscess' as Mesh terms or text in electronic databases of PubMed, Embase, and the Cochrane registry. The search was updated on 29 September 2022. Exclusion criteria were a sample size <10 patients or publication in non-English language. Extracted data was summarized as narrative reviews and tables. Meta-analysis was carried out using a random effects model and heterogeneity was examined by I 2 tests as well as funnel and Galbraith plots.
Conditional Very low ADC, apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted images; MRI, magnetic resonance imaging; TMP-SMX, trimethoprimsulfamethoxazole. Literature search, data synthesis, and risk of bias Key questions were agreed by the guideline panel during initial meetings and were formulated as Population, Exposure, Comparator, and Outcome (i. e. PECOs) for observational studies on management, and as Participants, Index test, Comparator test, and Reference standard for diagnostic studies. A broad literature search of scientific studies of 'brain abscess' or 'cerebral abscess' as text or Mesh terms was carried out by a medical librarian in the electronic databases of PubMed, EMBASE, and the Cochrane Library on 17 September 2021 and updated on 29 September 2022 (Full search strategy is available in Supplementary Material).
Studies were required to be published in the English language within the last 25 years and to have more than ten children or adults included, i. e. case reports were omitted. After automated removal of duplicates, 2887 studies were screened independently by two panel members (MCB and JB) and 460 were selected for full-text review (Fig. 1 ). Because five studies could not be retrieved, a total of 455 studies were reviewed in full length and tagged for potential relevance for each key question by the chair (Appendix 1). Groups of three to five panel members were assigned to each key question and separate data extraction tables were designed, piloted, and revised based on preliminary experiences. Next, raw data were obtained as relevant for individual PECOs including crude and adjusted measures of relative risk whenever available.
Data extraction was carried out by the chair except for key question #3 in which all three group members participated in this task. Risk of bias of individual studies for each key question was assessed independently by all members of the subgroup using ROBINS-I for observational studies and QUADAS-2 for studies on diagnostic accuracy (Appendices 2e9)  [43, 44]. Any discrepancies in these assessments were resolved by discussion. The scientific evidence was summarised as narrative reviews with key references and summary tables by the chair and discussed within subgroups. Aggregated data was analysed using a random effects model and heterogeneity was examined by the I 2 test [45e47]. Funnel and Galbraith plots were also created to assess true heterogeneity, selection (e. g. publication) and other biases, or chance according to study size  [48e51].
Few studies provided individual or group level data on specific antimicrobials and associated outcomes, or it was unclear if the described treatment was empirical or targeted. In consequence, all  studies reporting such detailed information were included into the analysis for guidance on choice of empirical antimicrobial treatment of brain abscess. There were no substantial differences in case-fatality rates between the examined empirical antimicrobial regimens in metaanalysis (Figs. 9e11 and S9eS14 and Table  S9 ). In one retrospective single-centre study of 59 immuno-competent patients with brain abscess, comparison was made between 3rd-generation cephalosporin and carbapenem-based regimens  [132]. The authors found that carbapenems were associated with decreased mortality after adjustment for Glasgow Coma Scale score, intracranial hypertension, and surgical treatment.
Notably, the groups were not well balanced in terms of age, calendar year, or number of patients with multiple brain abscesses, and residual confounding remains likely. Another study from Turkey provided detailed data on empirical and targeted antimicrobial treatment among 51 neurosurgically treated patients at a single centre and observed no differences in survival according to antimicrobial regimens  [153]. Moreover, case-fatality rates did not differ substantially between different antimicrobial treatments in several other smaller studies examining brain abscesses caused by certain groups of pathogens such as Streptococcus milleri, Streptococcus spp. , Gram-negative bacilli, and anaerobic bacteria  [85, 146, 147, 152]. Risk of bias was assessed to be critical for this key question in almost all the examined studies (Appendix 6).