dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements H. C. S. would like to acknowledge funding support from an  Imperial College Junior Research Fellowship. L. C. O. acknowledges funding from a  UK Royal Society Dorothy Hodgkin fellowship , the  Bill & Melinda Gates Foundation  and  Medicines for Malaria Venture. R. Pa. would like to acknowledge funding from the  Strategic Anopheles Horizontal Research Programme, Institut Pasteur. H. C. S. and L. C. O. acknowledge joint Centre  funding from the  UK Medical Research Council and Department for International Development.
Data availability All data used in this manuscript are provided as Source Data files, which are also deposited on dryad (https://doi. org/10. 5061/dryad. 75t5382), or in online repositories previously deposited by study principle investigator for each relevant study with original publication of data. Details of repositories are provided in the Source Data files on tabs relating to the relevant study. All data supporting the findings of this study are also available from the authors upon request.
Cell lysates were clarified by centrifugation at 4 °C and stored in aliquots at -80 °C. NuPAGE 4-12% Bis-Tris gels (ThermoFisher) were loaded with 2 μg of sample protein per lane and ran at constant voltage for 1. 5-2 h before blotting to either nitrocellulose or PVDF membrane using the iBLOT2 system (ThermoFisher). The antibodies used were anti-phospho-PDK1 (pSer241); anti-phospho-SGK (pSer422); anti-mTOR; anti-mTOR pSer2481 (SAB4504514, SAB4503834, SAB4501038, SAB4301526 Sigma-Aldrich); PDK1 (MA5-15797, ThermoFisher); SGK1; b-actin; anti-phospho-S6 ribosomal protein (Ser235/236) (#12103, #8457, #2211 cell signaling); and anti-p70 S6K (#05-781R, Millipore). Band intensities were quantified using ImageJ version 1. 51 software  (Schneider et al. , 2012).
Statistical analyses Statistical analyses To evaluate the mean axonal length of axons in differentiated SHSY5Y cells after each treatment, five pictures were taken for each condition and 20 axons were measured on each image, using the measure tool of the AxioVision Rel. 4. 8 software (Zeiss). For analyses of immunofluorescent staining, 6 to 16 pictures were taken for each condition using a Zeiss Axio Observer. Z1 microscope using a 20×/0. 35 or 40×/0. 5 objective. Quantification of fluorescent labeling and western band intensities was performed using ImageJ 1. 51. Statistical analyses were performed either by one-way ANOVA and subsequent Tukey's test for multiple comparisons or by Kruskal-Wallis test then Dunn's test, using GraphPad Prism v 6-7. Data were analyzed as ± standard deviation (SD), and a minimum p value of 0.
Flow cytometry Antibodies recognizing the following molecules coupled to the indicated fluorochromes were used to assess the purity of the cell' preparations: PE anti-Human CD8 (Hit8aOKT8, 50-0089-T100, Tonbo Biosciences), FITC anti-Human CD3 (OKT3, 35-0037-T100, Tonbo Biosciences), APC anti-Human CD45RO (UCHL1, 20-0457-T100, Tonbo Biosciences). Cells were subsequently washed twice in PBS containing 1% FCS and resuspended for FACS analysis. Flow cytometry was performed on the FACSCanto cytometer using BD FACSDiva software. Data analysis was performed using FlowJo software (FlowJo, LLC).
7 μm particle size) that was run at 35°C with the following gradient: 3-50 % Solvent B (0. 1 % formic acid in acetonitrile) in Solvent A (0. 1 % formic acid in water) for 30 min, 50-85 % B (1 min), 85 % B (7 min) and 3 % B (22 min). The separated peptides were directly electro sprayed into a linear ion trap LTQ Velos mass spectrometer (Thermo Fisher Scientific, Bremen, Germany) that was equipped with a nano-electrospray ion source and controlled by Xcalibur 2. 1 software. This spectrometer was operated in data-dependent acquisition mode, automatically alternating a full-scan (m/z 400-2000) spectrum with a collision-induced dissociation (CID) spectrum of the most abundant peptide ions. The data was analysed using the X!Tandem search engine on a LabKey or a Trans Proteome Pipeline  (Deutsch et al.
Protein analysis We performed functional analysis to the differentially -catenin associated proteins in nonstimulated or Wnt3a-stimulated conditions from neonate or adult CD8 + T cells. For this, we used the DAVID software (Database for Annotation, Visualization and Integrated Discovery) in connection with the KEGG PAHTWAY, UP KEYWORDS (Uniprot), GOTERM BP (Gene Ontology Consortium: Biological Process) and Interprot. We took Benjamini corrected p values for significant differences between neonatal and adult CD8 + T cell samples. For interactome analysis, we used String 10. 5 to predict protein interactions and visualized protein complexes with the Cytoscape 3. 5. 1 software.
Real time PCR For gene expression evaluation, cells were centrifuged, washed and placed in Trizol (Invitrogen, 15596-018, ThermoFischer) before freezing. RNA was extracted according to manufacturer's instructions. The integrity of the RNA was determined by electrophoresis and quantified with Qubit RNA HS kit in a Qubit fluorometer. cDNA was synthesized from total RNA using RevertAid reverse transcriptase (SO131 ThermoFisher). qPCRs were performed using SYBR Green PCR Master Mix (Life Technologies, 4309155, ThermoFisher). The mRNA levels were calculated with standard curves for each gene and were reported relative to those of GAPDH gene as standard. Specific oligonucleotides were designed to amplify regions corresponding to the mRNA of the genes (Suppl. Table  3 ). The mRNA sequence of the specific isoforms of the aforementioned genes was obtained from the NCBI database.
Subsequently, these sequences were entered into the Primer-BLAST online program to ensure specificity of the amplicon. For evaluation of the -catenin associated to specific gene promoters, chromatin immunoprecipitation analysis was performed, followed by qPCR. Specific primers in the gene promoters, containing TCF/LEF binding motifs, were selected using the "Eukaryotic Promoter Database" (EPD; http://epd. vital-it. ch/) to find promoters from the position -1000 to +100 of the gene. "Matinspector" analysis in www. genomatix. de allowed us to find the TCF-1/LEF-1 binding motifs. Regions with more than one motif were chosen. Oligos were obtained as described above, from a region -250 +250 of the motifs. Sequences are shown in Suppl. Table  3. All amplicons produced a single peak after denaturation, indicating a single amplicon.
platform, and the results were validated with PeptideProphet and ProteinProphet software. The fragmentation spectra were compared with theoretical two H. Sapiens Refseq databases that were obtained from NCBI: one with lymphocyte-related protein sequences and the other with proteins involved in the Wnt Signalling Pathway. The following search parameters were used: constant modifications, variable modifications, oxidized M. The ion-mass tolerances were 4 Da for precursor ions and 2 Da for fragmentation products. Two separate experiments.
In light of these data from PLS patients, we suggested that the pharmacological inhibition of CatC likewise lead to the elimination of the unprocessed pro-enzymes in mice. To investigate the fate of mouse zymogens of CatC in our experimental model after pharmacological inhibition, we stained paraffin-embedded sections of transplanted lungs with Ly-6G and NE antibodies to localize the distribution of neutrophils and NE (Fig. 3A ). All neutrophils were stained positive for NE revealing the presence of the NE protein in the transplanted lung. Moreover, PR3 and NE protein levels were not altered by ICatC treatment when whole lung tissue was analyzed by semi-quantitative Western blotting (Fig. 3B, C ). Full western blots are provided in supplementary information 2A,B. These findings were corroborated by quantitative measurements of the NE protein using a commercial ELISA.
Neutrophils that are devoid of neutrophil elastase are impaired in their formation of NETs  29. Moreover neutrophils from CatC deficient individuals are incapable of producing NETs (18) suggesting that multiple mechanisms contribute to the beneficial anti-inflammatory effects of the CatC inhibitor in our model. The major overall effect of CatC inhibition in ischemia-reperfusion response, however, remains to be clarified. Clinical potential of our translational approach. Patients on the LTx waiting list usually suffer from severe end-stage pulmonary disease and need special cost-intensive care and medical supervision. End-stage lung disease often deteriorates through chronic inflammatory processes as seen with cystic fibrosis, COPD, alpha-1-antitrypsin deficiencies, and bronchiectasis. The cathepsin C inhibitor INS1007, originally developed by AstraZeneca as AZD7986, an orally applicable drug, is currently assessed in bronchiectasis patients over a 24 week treatment period (ClinicalTrials.
gov Identifier: NCT03218917). In a preceding phase 1 study of healthy individuals, inhibition of CatC was well tolerated with only minor skin desquamation as side effects, but these were not considered to prevent further clinical studies  18. CatC inhibitors have been judged to be ethically acceptable for long term application; hence they may also be considered for administration to patients on the waiting list until transplantation, at least to those with bronchiectasis. With the pre-operative ICatC treatment of the recipient it would be possible to suppress the inflammatory response initiated by the local release of NSPs from infiltrating neutrophils in the patient before transplantation and in the transplanted lungs after surgery. Based on the average neutrophil maturation kinetics in humans, treatment with a CatC inhibitor will require drug exposure for less than 3 weeks to be efficacious in humans  18, 30.
Limitations of the mouse study. As the investigational novel drug INS1007 was not available to us for transplantation studies in mice, a functionally similar inhibitory substance, XPZ-01, was assessed by parental administration of two injections per day in this pilot study. Only one dose of ICatC was tested, which was chosen according to previous studies in primates and mice  20. Many data which are routinely monitored in the clinics cannot be recorded in a small animal transplantation model under different special challenges. We have not measured blood pH, carbon dioxide in the left pulmonary artery or right ventricle and graft compliance 4 hours after left lobe transplantation. Due to the highly challenging transplantation procedure in mice we studied only the outcome of primary graft function 4 hours after LTx.
The fixed lung tissues were embedded in paraffin and sectioned onto slides. Immunohistochemical and immunofluorescent stainings. Immunohistochemical staining for neutrophil granulocytes was performed on a Discovery XT automated stainer (Ventana Medical Systems, Tucson, AZ) employing a monoclonal rat mouse-specific Ly-6G monoclonal antibody (1:200, clone 1A8, Biolegend), with Discovery Universal (Ventana Medical Systems, Tucson, AZ) as the secondary antibody. Signal detection was conducted using the peroxidase/diaminobenzidine reaction (Ventana Medical Systems, Tucson, AZ). The stained tissue sections were scanned with an AxioScan. Z1 digital slide scanner (Zeiss, Jena, Germany) equipped with a 20× magnification objective. Images were evaluated using the commercially available image analysis software Definiens Developer XD 2 (Definiens AG, Munich, Germany) following a previously published procedure (30).
The calculated parameter was the number Ly-6G postive stained cells per mm 2 tissue. For immunofluorescence staining, lung tissues were analyzed by a double staining for neutrophil granulocytes (1:200 monoclonal rat anti-mouse Ly-6G, clone1A8, Biolegend; 1:400 AlexaFluor ® 647 -goat anti-rat A21247, Thermo Fisher Scientific, USA) and for neutrophil elastase (1:1000 polyclonal rabbit anti-neutrophil elastase, ab68672, Abcam, UK; 1:100 Cy3-goat anti-rabbit A10520, Thermo Fisher Scientific, USA). Nuclei were identified with Hoechst 33342. Fluorescence stainings were photographed with an Axio Imager Z1 (Zeiss) and visualized with the Axio Vision 4. 6. 3 software (Zeiss). protein analyses by Western blot and elisa. The total protein concentration of PMN lysate, BALF and whole lungs in RIPA lysis buffer (50 mM Tris, 150 mM NaCl, 1 mM EDTA, 0.
Mouse elastase concentrations in whole cell lysates and IL-6 levels in BAL fluid were quantified by ELISA (PicoKine TM Elisa, (EK1445), Multi Analyte ELISArray Kit (MEM-004A)) and conducted as described in the manufacturer's recommendations. statistical analysis. All results are expressed as mean ± SEM. Group comparisons were determined by student's t-test or unpaired Mann-Whitney U-test using the commercially available statistical software GraphPad Prism version 5. 0. Statistical significance was defined as p ≤ 0. 05.
DNA sequencing and phylogenetic analysis PCR products were purified with ExoSAP-IT kit (Affymetrix, Cleveland, OH, USA), following the manufacturer's instructions, and purified products sequenced at the Macrogen DNA Sequencing Service (Rockville, MD, USA). For phylogenetic analysis, maximum likelihood (ML) phylogenetic trees based on Rickettsia 23S-5S rRNA ITS and ompA gene sequences were inferred using Molecular Evolutionary Genetics Analysis (MEGA) software, v. 6  [19]. Sequences were collected in GenBank to represent different Rickettsia species (using 23S-5S rRNA ITS and ompA) and strains (using ompA) as shown in results. Sequences were aligned with MAFFT (v. 7) configured for the highest accuracy using the scoring matrix 200PAM/kD2, alignment strategy MAFFT-FFT-NS-I, gap opening penalty 1.
Results Out of 300 free-roaming dogs enrolled in the present study, 253 were infested by ticks, which corresponds to an overall infestation rate of 84. 3% (95% CI: 80. 2-88. 4%). All ticks collected were morphologically identified as R. sanguineus (s. l. ). In total, 1238 specimens were collected, of which 1063 (85. 9%) were engorged females and 175 (14. 1%) engorged nymphs. Out of 30 pools tested, six (each six females) were found to be positive to Rickettsia spp. DNA (Table  2 ), with an MIR of 3. 3% (95% CI: 1. 2-7. 1%). By BLAST analysis, the sequences obtained from ticks collected in Francisco I. Madero, Torreon and Viesca presented 99% identity to different sequences of R. rickettsii from the USA (GenBank: U11022, CP003311 and CP018914). Two sequences from San Pedro and one from Torreon showed 99% identity to Rickettsia rhipicephali from south-eastern Brazil (GenBank: KT340606), New Mexico (USA) (GenBank: CP013133) and North Carolina (USA) (GenBank: CP003342).
Acknowledgements We thank the residents of the municipalities where this study was performed. We are also in debt to  Alfonso Lomelí-Juárez  for his assistance during tick collections and to  Lucas C. de Sousa-Paula  ( Aggeu Magalhães Institute, Fiocruz, Brazil ) for elaborating Fig. 1. Publication of this paper was sponsored by  Bayer Animal Health  in the framework of the 14th  CVBD World Forum Symposium.
Statistical analysis Kruskal-Wallis one-way analysis of variance followed by Bonferroni-Dunn correction of the post hoc tests was used to analyze quantitative differences of messanger ribonuclein acid (mRNA) transcripts. Data are presented as mean ± standard error of the mean. The level of significance was set at p < 0. 05. GraphPad Prism 5. 02 software (GraphPad Software, Inc, La Jolla, CA) was used for statistical analysis.
, 2012)  and mesenchymal stem cell-like pericytes  (Ochs et al. , 2013) , thereby reflecting GBM cellular heterogeneity. We recently demonstrated that CD90 expression is not only restricted to GBM stemlike cells but is also observed in more differentiated GBM cells (primary adherent lines) and in freshly dissociated GBM specimens  (Avril et al. , 2017a). Using the recent single-cell RNA sequencing datasets from stem-like and no-stem GBM cells and tumor migrating cells  (Darmanis et al. , 2017; Cook et al. , 2018) , we confirm herein that CD90 is expressed in tumor cells from the cancer site but also in migrating tumor cells, tumor-associated endothelial cells, and neighboring neuronal cells (Figure  2C ). CD90 expression in kidney cancers is currently controversial. Primary cell lines and tumor stem cells from pediatric Wilms' tumors and metastatic renal tumors express CD90  (Pode-Shakked et al.
These different elements underline the complexity of CD90 functions in cancer, depending on both the cellular context and on the tumor microenvironment. Future studies will lead to the better understanding of CD90 regulation and functions adding to the information already available such as the CD90 mutation spectrum as seen in COSMIC/cBioPortal; the IRE1-controlled CD90 tumor expression and functions with a clarification of the involvement of the IRE1 downstream signaling pathways XBP1s and/or RIDD branches; and the relevance of cleaved CD90 released in the tumor microenvironment. and Entrepreneurship, " Priority Health of the Peripheral Entrepreneurial Program of Attiki to AC. CS was funded by a post-doctoral fellowship from the Plan Cancer.
FUNDING This work was funded by  la Ligue contre le Cancer  (comités 35, 56 et 37) to TA; grants from  INSERM, Institut National du Cancer (INCA) ,  Région Bretagne ,  Rennes Métropole ,  Fondation pour la Recherche Médicale (FRM)  to EC;  EU H2020 MSCA ITN-675448  (TRAINERS) and  MSCA RISE-734749 (INSPIRED)  to EC and AC; PROMISE, 12CHN 204  Bilateral Greece-China Research Program of the Hellenic General Secretariat of Research and Technology  and the  Chinese Ministry of Science and Technology  sponsored by the  Program "Competitiveness.
Methods Because of insufficient exhaustiveness, the mandatory reporting of gonorrhoea, syphilis and LGV cases was replaced in 2000 by sentinel surveillance networks based on biologically confirmed case definitions (Figure  1 )  [1]. RésIST, the network of clinicians coordinated by Santé publique France (the French national public health agency), contributes to the surveillance of early syphilis (primary, secondary or early latent stages) and gonorrhoea. The collection of demographic, clinical, biological and behavioural data relies on practitioners working in different diagnostic centres (STI clinics, dermatological hospital consultation units, infectious illness consultation units, internal medicine or private medical practices). Nevertheless, the majority of syphilis (82. 8%, n = 1,447) and gonorrhoea (95%, n = 2,389) cases reported in 2016 by the RésIST network were diagnosed in STI clinics and the coverage of this network is unknown.
Standardised hardcopy forms are completed by physicians for each confirmed case. Rectal LGV (infection due to the serovar L strain of Chlamydia trachomatis) is monitored via a sentinel network of laboratories, coordinated by the national reference centre (NRC) for chlamydial infections which collects biological and demographic data. They are completed with clinical and behavioural data collected through a standardised hardcopy form sent to the prescribing clinicians by the NRC. LGV: lymphogranuloma venereum; NRL: national reference laboratory. of cases with, respectively, chlamydial and gonococcal infection. The rates of coverage of these two networks were estimated at 18 and 23%, respectively, of the incident diagnoses confirmed in France in 2012  [2]. Since 2014, biologists have to fill a standardised online form instead of a paper questionnaire.
Infection in several anatomical locations in the same individual counted as one infection. Patients' characteristics (sex, age, residence, sexual orientation, presence of symptoms, type of specimen, HIV status, type of diagnostic centre) described, when information was available, here apply to the last year of the study period (2016). We chose the age groups in our analyses so as to match the national chlamydia screening recommendation (systematic screening for women < 25 years and men < 30 years). LGV, RésIST and Rénago/Rénachla networks were approved by the French Personal Data Protection Authority (CNIL authorisation, respectively no. 10362, 902057 and 999298). Patients' informed consent was required before any data collection. The number of people that opt out from this surveillance system by not providing their consent is unknown.
Several laboratories with a high level of activity reported difficulties to timely use the online individual questionnaire to report chlamydial infections. To maintain their participation to the network, they were LGV LGV (consistent diagnostic centres) LGV: lymphogranuloma venereum. invited to provide an electronic when it was possible, despite the loss of information for example about the presence of symptoms. A database uploading system might partly fix these problems and help sustain a good level of participation to the sentinel surveillance networks. Concerning the decrease in syphilis cases, the national shortage of benzathine penicillin in 2016 might have changed syphilis patients' healthcare seeking patterns, away from STI clinics to hospitalbased facilities where penicillin was still available.
84; Kircher et al. , 2014; Itan et al. , 2015 Itan et al. , , 2016)). Finally, we tested a model of autosomal recessive (AR) inheritance and focused our attention on genes with homozygous or compound heterozygous lesions. In P1, we found a private homozygous mutation in IFNAR1, c. 674-2A>G, among 48 variants in 39 genes (Table  S1 ). In P2, 11 variants in 6 genes passed filtering criteria (Table  S1 ), including two variants in IFNAR1, c. 783G>A; p. W261X and c. 674-1G>A (Fig. 1 C ). None of these three IFNAR1 variants are found in online databases including 1000 Genomes, Bravo, and GnomAD (Genome Aggregation Database), which encompasses the Exome Aggregation Consortium database (Fig. 1 D ). The IFNAR1 gene, together with IFNAR2, encodes the heterodimeric receptor for the type I IFNs  (Uzé et al.
WES Exome capture was performed with the SureSelect Human All Exon 50 Mb kit (Agilent Technologies). Paired-end sequencing was performed on a HiSeq 2000 (Illumina) generating 100-base reads. We aligned the sequences with the GRCh38 reference build of the human genome using the Burrows-Wheeler Aligner  (Li and Durbin, 2009). Downstream processing and variant calling were performed with the Genome Analysis Toolkit, SAMtools, and Picard  (Li et al. , 2009; McKenna et al. , 2010). Substitution and InDel calls were made with GATK Unified Genotyper. All variants were annotated using an annotation software system that was developed in-house  (Ng and Henikoff, 2001; Adzhubei et al. , 2010; Kircher et al. , 2014).
Genetics WES analysis of each patient revealed a total of 16,797 variants in P1 and 50,634 variants in P2. We filtered out all variations found in 1000 Genomes database, GnomAD, and our own database of 4,892 exomes for infectious diseases at a frequency of >1%, leaving 48 and 11 nonsynonymous coding variants in P1 and P2's exomes, respectively: 30 and 6, respectively, were homozygous, and 18 and 5 were heterozygous. The heterozygous variants inherited from one parent were not considered in a model of complete penetrance. Excluding those in IFNAR1, none of the variants affected genes known to be related to immunity. The nonsense c. 783G>A mutation had a CADD score of 37, and the two splicing mutations, c. 674-1G>A and c. 674-2A>G, had CADD scores of 23. 6 and 24, respectively. A genomic measure of individual homozygosity was plotted for P1 and P2, two European individuals from consanguineous families, and 37 individuals from nonconsanguineous families from our in-house WES database.