dataesr/scientific-paragraphs-categorization huggingface dataset:
Patients and Tumor Samples Inclusion criteria were a minimum age of 18 years and availability of clinical and survival data. Glioma samples were obtained from 64 adult patients who underwent surgery at Limoges and Montpellier University Hospitals from 1993 to 2013 and did not have any treatment such as chemotherapy and radiotherapy. Clinical and survival data were obtained by a retrospective query, and all samples were used in accordance with French bioethics laws regarding patient information and consent. This study benefited from the expertise of Prof. Labrousse (collection manager of Limoges), Prof. Rigau (collection manager of Montpellier) and Prof. Sylvain Lehmann (manager of the Biological Resource Center of Montpellier University Hospital (CRB-CHUM)). Gliomas were classified according to the 2016 WHO classification.
Detection of 1p and 19q Chromosome Arm Loss or Retention by Multiplex-Ligation-Proximity Assay The multiplex-ligation-proximity assay (MLPA) technique was used to analyze 1p and 19q chromosome arm loss or retention, according to the manufacturer's recommendations (SALSA ® MLPA ® P088-C2 Oligodendroglioma kit, MRC-Holland, Amsterdam, The Netherlands). Probe sequences and locations are available on the manufacturer's site. Briefly, after MLPA experiments, denatured fragments were separated according to their size by capillary electrophoresis on an ABI 3130XL capillary sequencer (Applied Biosystems, Waltham, MA, USA) and peak heights were quantified by GeneMapper software (Applied Biosystems). Data analysis was performed using an in-house Microsoft Excel matrix as previously described  [47, 48].
TaqMan Low-Density Array Design: The custom-made TaqMan low-density array (TLDA) card contained 4 identical 96-gene sets including glioma markers, genes coding for neurotrophins and their receptors and genes involved in different mechanisms such as glycosylation, autophagy, receptor tyrosine kinase signaling, hypoxia and angiogenesis (Applied Biosystems). The complete list is available in Supplementary Table  S4. Each card contained housekeeping genes: HPRT1, 18S, GAPDH and β2-microglobulin. Interexperiment reproducibility was verified on 4 samples that were analyzed twice, and intraexperiment reproducibility was verified by duplicate amplification of a single gene (PRUNE2 or KIAA0367). The amplification protocol and data analysis were carried out as previously described by Ermonval et al.
Thus, from the expression levels of the 92 genes, a subset of genes able to discriminate between WHO grades was selected on the basis of 2 statistical analyses: (i) Genes showing a significant difference between grade II, III and IV tumors by t-test (p < 0. 05); and (ii) genes highly correlated with grade II, III or IV tumors. Principal component analysis (PCA) was performed with the FactoMineR package  [52]  and hierarchical clustering (HC) with the ComplexHeatmap package  [53]. To distinguish low and high expression of a gene, the median cutoff was chosen as previously described in the literature  [54].
Validation of Gene Expression Profiling The classification of gliomas by PCA and HC based on our expression dataset was validated in an independent cohort of glioblastoma and grade II and III datasets from The Cancer Genome Atlas (TCGA) project. Normalized (RSEM method) and batch-corrected RNAseq expression data corresponding to whole gliomas (named GBMLGG cohort) were downloaded from the Firehose portal of the Broad Institute (gdac. broadinstitute. org). Clinical information, IDH mutation, and 1p19q status were also retrieved from the Broad GDAC portal. All clinical data were downloaded from the TCGA portal. Gliomas were classified according to the 2016 WHO classification.
Statistical Analysis Data were analyzed using Statview ® (SAS Institute Inc. , Cary, NC, USA) and R (www. r-project. org). Quantitative results were expressed as means ± SD. Percentages and medians were compared using parametric or nonparametric tests for ordinal variables depending on the size of the group (chi-squared test, Mann-Whitney test, Kruskal-Wallis test, Student t-test). Overall survival (OS) was calculated from the date of initial surgery/biopsy to the date of death or last follow-up. Logistic regression was used to analyze the factors associated with IDH status. Survival curves were obtained using the Kaplan-Meier method. Relevant variables associated with OS were examined using univariate and, where applicable, multivariate Cox proportional hazards regression. For the multivariate models, a univariate inclusion criterion of p ≤ 0.
This information not only provides experimental validation of hydrogen-bonding interactions inferred from x-ray structures but also adds over x-ray data in cases where positions of hydrogen atoms were predicted inaccurately or were not known. Furthermore, it describes the organization of water molecules by accurately determining their orientations. Here, we present previously unidentified atomic details of phosphoryl transfer by PKA-C. We determined a room temperature neutron structure of the PKA-C subunit trapped in a product complex that contains adenosine diphosphate (ADP), a phosphorylated protein kinase substrate (pPKS) peptide, and two metal ions. We observed a protonated phosphate group on the product substrate and deprotonated catalytic Asp 166 , whose protonation states were previously unknown.
An increase in the φ factors, for the same group of amides, was observed in the NMR sets of apo and/or binary (with Mg 2 ADP) PKA-C complexes relative to the ternary, PKA-C:Mg 2 ADP:PKI, cluster. Globally, this correlates with the enzyme transitioning from closed (ternary) to open (apo) or semiopen (binary) conformations, weakening of hydrogen bonds, and different dynamics  (15, 21, 37). In the neutron structure of PKA-C:Sr 2 ADP:pPKS, the enzyme is in its intermediate or semiopen conformation. We suggest that the difference in the H/D pattern observed in the neutron dataset is due to the neutron structure representing products rather than substrates and might be an indication of altered dynamics between the two complexes. This comparison provides a hypothesis that can be tested in future studies.
Data collection and structure refinement The preliminary neutron diffraction data at room temperature were collected on the IMAGINE (39) instrument located at the High Flux Isotope Reactor (Oak Ridge National Laboratory) from a 0. 1-mm 3 crystal of deuterated PKA-C:Sr 2 ADP:pPKS. The complete room temperature quasi-Laue dataset to 2. 5 Å resolution was collected on the LADI-III beamline at the Institut Laue-Langevin  (40). A summary of the experimental and refinement statistics is given in table  S3. Table  S4  provides the references for the software used in data collection and structure refinement. In total, 30 diffraction images were collected (with an average exposure time of 24 hours per image) from two different crystal orientations. The neutron data were processed using the Daresbury Laboratory LAUE suite program LAUEGEN modified to account for the cylindrical geometry of the detector.
The program LSCALE was used to determine the wavelength-normalization curve using the intensities of symmetry-equivalent reflections measured at different wavelengths. No explicit absorption corrections were applied. These data were then merged in SCALA. Monochromatic x-ray diffraction data were collected on a different crystal from the same crystallization drop using an in-house Rigaku HomeFlux system, equipped with a MicroMax-007 HF generator, Osmic VariMax optics, and an R-AXIS IV++ image-plate detector. Diffraction data were collected, integrated, and scaled with the HKL-3000 software suite. The structure was solved by molecular replacement with CCP4 suite using the hydrogenous PKA-C:Sr 2 ADP:pPKS complex [Protein Data Bank (PDB) ID 4IAY] as a starting model. The room temperature x-ray structure of deuterated PKA-C:Sr 2 ADP:pPKS at a resolution of 2.
The level of H/D exchange at OH, NH, and SH sites was refined. All H positions in deuterated PKA-C and labile H positions in the ligands (ADP and pPKS) were modeled as D, and then the occupancies of D were refined within the range of -0. 56 to 1. 00 (the scattering length of H is -0. 56 times the scattering length of D; the amount of D at each position is then calculated as [(D occupancy + 0. 56)/1. 56]). Before depositing the final structure to the PDB, a script was run that converts a record for the coordinate of D atom into two records corresponding to H and D atoms partially occupying the same site, both with positive partial occupancies that add up to unity. The joint XN structure of deuterated PKA-C:Sr 2 ADP:pPKS has been deposited to the PDB (ID 6E21).
Methods Participants. 30, 20, 50, 30, 20 and 15 participants (age range: 18-35 years; 69% of females) were respectively recruited for experiments 1 to 6. The experiments followed the local ethics guidelines from Aix-Marseille University. Informed consent was obtained from all participants before the experiments. All had normal audition and vision and reported no history of neurological or psychiatric disorders. We did not select participants based on musical training. Experimental design of the auditory experiments (n°1, 2 and 6). Auditory stimuli were sampled at 44 100 Hz and presented binaurally at a comfortable hearing level via headphones (Sennheiser HD 250 linear) in an anechoic room, using the Psychophysics-3 toolbox  88  and additional custom scripts written for MATLAB (The Mathworks).
Overview We did a multi-component investigation into Zika virus and suspected microcephaly cases in Angola. We assessed surveillance data from the Ministry of Health in Angola to identify acute cases of Zika virus infection confirmed by real-time reverse transcription PCR (RT-PCR) between December, 2016, and October, 2018. To identify additional real-time RT-PCR samples positive for Zika virus that are appropriate for sequencing, we also screened samples from 349 people with HIV living in Luanda, Angola, in 2017. We sequenced Zika virus from three samples and did phylogenetic analysis to elucidate the origins and duration of the Angolan outbreak. We analysed human air travel and data on the global incidence of Zika virus infection to support our findings about the geographical source of the introduced strain.
Research in context Evidence before this study We searched PubMed with the keywords "Zika" and "Africa" for papers published in any language up to Oct 31, 2018. We also checked available Situation Report publications from WHO up to the same date for evidence of Zika virus or congenital Zika disease in Africa. The African lineage of Zika virus has been detected in Africa since the mid 20th century, yet evidence for spread of the Asian lineage of the virus is scarce. Two countries in Africa (Cape Verde and Angola) have reported cases of Zika virus infection that are thought to have been caused by a newly introduced Asian lineage virus. Sequence data are crucial to confirm and understand the spread of Asian lineage Zika virus in Africa, but these data are currently limited to a single 193 bp fragment of the Zika virus NS5 gene from Angola.
Phylogenetic analyses We did phylogenetic analyses to explore the probable geographical and temporal origins of the Zika virus outbreak in Angola, and the minimal duration of local transmission. We used Muscle to align the three new Zika virus genomic sequences with 390 other viral genomes publicly available from GenBank. 20 We used PhyML (version 3. 1) to estimate maxi mum likelihood phylogenies  21  and BEAST (version 1. 10. 3) to estimate molecular clock phylogenies (appendix p 5). 22.
Origins of Angolan Zika virus outbreak An outbreak of Zika virus infection was reported in Cape Verde in 2015-16, from which no genetic sequence data are available. 7 The absence of genetic data from locations that have reported Zika virus and are connected to Angola by air travel meant that we could not unambiguously infer the geographical origin of the Angolan outbreak with phylogenetic analysis alone. We therefore analysed the global incidence of Zika virus infection and human mobility data to independently investigate the probable source of Zika virus in Angola. Two factors were considered here as contributing to a high risk of exporting the virus to Angola: a high local incidence of Zika virus and high numbers of air passengers travelling to Angola. The monthly number of passengers to Angola from countries reporting Zika virus was estimated on the basis of worldwide ticket sales data from the International Air Transport Association for Jan 1, 2015, to Dec 31, 2017.
Results Between December, 2016, and October, 2018, serum samples were collected from 54 patients with sus pected Zika virus, who were notified to the Angola Ministry of Health after clinical examination (appendix p 12). Three cases of Zika virus infection were detected by routine surveillance using real-time RT-PCR (figure  1 ). The earliest case detected by routine Ministry of Health surveillance was identified in December, 2016, (immediately after real-time RT-PCR surveillance was initiated), and the latest in May, 2017. Data for the time between presence of symptoms and collection of the sample were available for two positive cases (figure  1 ). Although suspected cases of Zika virus infection were reported across Angola (figure  2A ), all confirmed cases of Zika virus infection were residents of, or had travelled to or through, Luanda or the neighbouring province of Bengo (figures 1, 2A).
Namibia Maximum likelihood phylogenies suggested that the three Zika virus strains formed a single, well supported monophyletic clade within the Asian lineage of Zika virus that is circulating in the Americas (bootstrap score 0•96; appendix p 9). Thus, the Zika virus outbreak in Angola probably resulted from a successful introduction of the virus followed by autochthonous transmission within Angola. Our phylogenetic analyses suggest that Zika virus was probably introduced to Angola from Brazil (figure  3 ), possibly from the southeast of Brazil, where the most closely related virus to the Angola Zika virus clade was sampled (accession number KY559016; posterior prob ability 0•99). The estimated date of the most recent common ancestor of the Angola Zika virus sequences is June, 2016 (Bayesian 95% credible interval January-October, 2016; figure  3 ).
Discussion In this multi-component outbreak investigation, we characterised the first known outbreak of Asian lineage Zika virus in continental Africa. Although surveillance, genetic, and clinical data were individually scarce, together these independent lines of evidence provide a cohesive picture of the outbreak of Zika virus infection in Angola. We report data for five cases of Zika virus infection between December, 2016, and October, 2017, and confirmed by real-time RT-PCR. The three Zika virus genomes that we sequenced represent the first Asian lineage genomes reported from Africa, and the first genome isolated from a case with Zika-virus-associated microcephaly in Africa. Our phylogenetic analyses showed that Zika virus was probably introduced to Angola from Brazil and then circulated for 17-28 months.
Acknowledgments We thank the participants who participated in this study and the  WHO Angolan country office  for sharing information about suspected  Zika For GitHub  see https://github. com/arbospread/Zika_Angola/ and microcephaly cases. This research was supported by a  Sir Henry Dale Fellowship  ( 204311/Z/16/Z ), internal  Higher Education Funding Council for England Global Challenges Research Fund  ( 005073 ), the  Africa Oxford Initiative  (AfiOx-48 and AfiOx-60),  John Fell Research Fund  ( 005166 ), and by the  Medical Research Council  ( MR/S0195/1  and  2018/14389-0 ), O  Conselho Nacional de Desenvolvimento Científico e Tecnológico  ( 440900/2016-6  and  440685/2016-8 ),  Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior  ( 88881. 130757/2016-01 , 88887. 130716/2016-00 ,and  88881.
130728/2016-01 ), the  European Research Council  ( FP7  grant agreement  614725-PATHPHYLODYN ), and the  Oxford Martin School. C-HW  is supported by the  UK Medical Research Council and Cancer Research UK  ( ANR00310 ). We thank  Patrícia Alvarez Baptista  and  Antonio Gomes Pinto Ferreira  ( Fundação Oswaldo Cruz, Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos, Rio de Janeiro, Brazil ) for donating Bio-Manguinhos reagents, and  Jorge Muñoz-Jordan  and  Gilberto Santiago  ( CDC ) for donating real-time reverse transcription PCR reagents.
casei BL23 developed tumors, compared to 100% of mice receiving either PBS or L. lactis MG1363 (Figure  1A ). These results confirm the absence of any positive effect of L. lactis MG1363, which is consistent with previous reports  (Bermudez-Humaran et al. , 2005; Cortes-Perez et al. , 2007). We then determined bacterial location after i. n. administration using Syto 9 bacterial staining. We mainly found L. casei BL23 in NALT and stomach (Figure  1B ) 24 h and 48 h after administration. Despite a higher L. casei BL23 concentration was observed (2069 events/µl as mean in NALT vs. 950 events/µl as mean in stomach) in NALT than in stomach 24h post inoculation; we compared the effect on tumor onset in function of the route of bacterial administration (oral vs. i. n. ). We confirmed previous data obtained with recombinant bacteria showing no protective effect following oral bacterial administration (Figure  1C ).
NK Cells Mediated a Cytotoxic Effect of L. casei BL23 Toward Cancer Cells Because of the well-known role of IL-2 in NK cell proliferation and the cytotoxic activities of these cells on tumor development  (Takagi et al. , 2001) , we assessed the systemic expression of NK cells. A negative correlation between tumor size and NKP46+ cells was found confirming the necessity of NK cells in tumor protection (r 2 = -0. 86, p < 0. 0001, Supplementary Figure  S3H ). More interestingly, there was a significant negative correlation between local NKp46 expression and tumor size (r 2 = -0. 94, p = 0. 016, Supplementary Figure  S3I ). This correlation was specific to L. casei BL23 treatment since no correlation was observed between NK cells and tumor size in control PBS-treated mice (data not shown). We further analyzed cytotoxicity activity of NK on TC-1 cells in vitro.
Isolation and growth conditions In April 2016, an unidentified bacterial strain was isolated from the human ileum of a patient with Crohn's disease and provisionally named Ileibacterium massiliense  [7]. Tentative identification was done using MALDI-TOF MS on a Microflex LT spectrometer (Bruker Daltonics, Bremen, Germany) as previously described  [8]. The obtained spectra (Fig. 1 ) were imported into MALDI Biotyper 3. 0 software (Bruker Daltonics) and analysed against the main spectra of the bacteria included in two databases (Bruker Daltonics) and constantly updated MEPHI databases (http://www. mediterranee-infection. com/ article. php?larub=280&titre=urms-database). This strain was cultured routinely on Columbia sheep-blood agar (Biomerieux, Marcy l'Etoile, France) at 37°C under anaerobic conditions.
Strain identification To identify this bacterium, the 16S rRNA gene was amplified using the primer pair fD1 and rP2 (Eurogentec, Angers, France) and sequenced using the Big Dye® Terminator v1. 1 Cycle Sequencing Kit and 3500xLGenetic Analyzer capillary sequencer (Thermofisher, Saint-Aubin, France) as previously described  [9]. The 16S rRNA nucleotide sequence was assembled and corrected using CodonCode Aligner software (http://www. codoncode. com). The 16s rDNA gene sequence of strain Marseille-P3115 exhibited a 90. 7% sequence similarity with Mogibacterium neglectum ATCC700924 T (GenBank accession no. AB037875), the phylogenetically closest species with a standing in nomenclature (Fig. 2 ). We consequently classify this strain as a member of a new species within the new genus Alterileibacterium, family Clostridiales XIII.
Genomics Genomic DNA of the bacterium was sequenced using the MiSeq Technology (Illumina Inc, San Diego, CA, USA) with the matepair strategy as previously described  [10]. Total information of 5. 1 Gb was obtained from a 544K/mm 2 cluster density with a cluster passing quality control filters of 96. 8% (10 139 000 passing filter paired reads). Within this run, the index representation for A. massiliense was determined to 4. 43%. The 449 618 paired reads were trimmed using the Trimmomatic software  [11] ; GapCloser  [12]  was used to reduce gaps, then assembly was carried out with the Spades software  [13]  in two scaffolds. The genome of strain Marseille-P3115 is 1 450 823 bp long with a 35. 9 mol% G+C content. The degree of genomic similarity between A. massiliense strain Marseille-P3115 and closely related species was estimated using the OrthoANI software  [14].
Values among closely related species (Fig. 4 ) ranged from 63. 39% between Eubacterium saphenum strain ATCC49989 T (GenBank ACON01000001) and Eubacterium pyruvativorans ATCC BAA-574 T (GenBank FNBF01000001. 1) to 83. 43% between Mogibacterium diversum ATCC700923T (RefSeq NZ_CP027228. 1) and Mogibacterium pumilium ATCC700696 T (RefSeq NZ_CP016199. 1) When the isolate was compared to these closely related species, values ranged from 64. 02% with Eubacterium pyruvativorans ATCCBAA574 T (GenBank FNBF01000001. 1) to 68. 04% with Mogibacterium timidum ATCC33093 T (GenBank JALU01000001. 1).
Acknowledgments:  Manuel Scimeca  is the recipient of a fellowship from the  "Fondazione Umberto Veronesi" (FUV). Rita Bonfiglio  is the recipient of a fellowship from  "Centro Universitario Cattolico" (CUC). We would like to thank  Harpreet Kar Lamsira  for the language editing. Authors wish to thank  Mirco Polletta  for drawing the Graphical Abstract.
This model consists in a 3D-printed adult upper airways replica connected to a porcine respiratory tract placed in a sealed enclosure. This experimental set-up allow to induce passive ventilation of lungs by inducing negative pressures within the enclosure (applying the same physical principle as intrapleural negative pressures observed in human breathing). Breathing pattern are easily and reproducibly controllable. Two RR were tested (i. e. 15 and 25 cycles/min) to experimentally assess 5 respiratory physiological measurements: MIF, TV, MV, R and C. Results obtained demonstrated that the breathing pattern of the IPF ex vivo model was varying in the same magnitude compared to in vivo data of IPF-suffering patients. Then, 81m Kr planar scintigraphies were used to assess homogeneity of gas-ventilation of the developed IPF ex vivo model.
Materials. A stereolithographied adult replica of upper airways, including larynx, was made by three-dimensional printing technology. This Ear-Nose-Throat (ENT) replica was obtained by reconstruction from CT scan images of a healthy subject. Data were obtained from Saint-Etienne teaching hospital. At arrival each patient received an information note explicitly stating that their date could be used for research purposes. Furthermore, written consent from patient is obtained in the Radiology ward. Lastly, use of such data was supervised by the Ethic Committee of Saint-Etienne hospital. It integrated laryngeal structures to mimic vocal folds resistance. This 3D-printed replica was anatomically, geometrically and aerodynamically validated using several techniques (endoscopy and CT scans) and was previously used for several nasal and pulmonary aerosol deposition studies  41, 42, 49, 57.