dataesr/scientific-paragraphs-categorization huggingface dataset:
All sporozoite reads were aligned directly to the P. vivax reference genome and processed with the same parameters as described above. De novo transcript assembly. We used all non-duplicated reads that mapped to the P. vivax reference genome to de novo assemble transcripts with Trinity 38 (version 2. 1. 1) using the stranded library option (-SS_lib_ type RF). Each sample was processed and analyzed independently. All de novo assembled transcripts were then mapped to the P. vivax PlasmoDB reference genome with GMAP 39 using -k 13 (a kmer of 13), -n 0 (chimeric transcripts are given two paths) and -f sampe (paired-end read data). In a separate analysis, we combined all non-duplicated reads from all three clinical infections in a single dataset and de novo assembled transcripts using the same parameters as above.
We calculated the read coverage for each transcript, taking into account the strand information: we first separated + and -encoded transcripts based on the GMAP output as well as + or -strand-originating reads based on the initial Tophat mapping. We then used Bowtie2 to align + strand read pairs to + strand transcripts, and -strand read pairs to -strand transcripts. Chimeric transcripts that aligned to two different places in the genome were split and handled as separate transcripts. Protein-coding gene predictions. We used Transdecoder 40 (version 3. 0. 0) to predict open reading frames (ORFs) from each de novo assembled transcript and determine its encoding amino acid sequence. We used the default settings and only considered ORFs encoding for at least 100 amino acids. We further filtered the results and only considered the longest predicted protein-coding sequence of each transcript.
Based on these results, we classified each de novo transcript into one of three categories: complete protein-coding genes for transcripts containing a start and stop codon, partial protein-coding genes (lacking either a start codon, a stop codon, or both), and noncoding genes (i. e. , for transcripts encoding less than 100 amino acids). Comparison with current P. vivax annotations. To compare the amino acid sequences of the predicted protein-coding genes with the current P. vivax protein annotations, we used reciprocal BlastP searches. First, we used BlastP to find, for each predicted protein-coding transcript, the most similar annotated protein(s) in the P. vivax reference genome. Then we did the reverse operation to find the most similar predicted protein-coding transcript(s) for each annotated P.
vivax gene. For both BlastP analyses, we considered amino acid sequences that were more than 90% identical over more than 90% of the length and with an e-value < 0. 001. If one transcript and one annotated gene matched each other reciprocally, we classified the predicted protein-coding gene as previously annotated. If one transcript and one annotated gene matched each other only in one search, and not the reciprocal search, but mapped to the same genomic location, we interpreted the predicted protein-coding gene as a protein isoform or a possible misannotation. Finally, if one transcript did not match any annotated protein-coding gene in either search, we classified the transcript as a potentially novel protein-coding gene.
We considered any transcripts mapping to the same location but with different encoding amino acid sequences as potential protein isoforms. To identify variations in 5′-or 3′-UTR, we looked for transcripts with identical protein-coding sequences but differences in 5′-or 3′-ends greater than 50 bp. Noncoding RNAs. All transcripts without an ORF of at least 100 amino acids were categorized as noncoding. We used BlastN searches against the entire nt NCBI database to find similarity between these transcripts and annotated rRNA, snRNA, snoRNA and tRNA. We defined antisense noncoding RNAs as transcripts that overlapped known P. vivax protein-coding genes over at last 30% of their length but on the opposite strand.
Acknowledgements We would like to thank all patients and healthcare workers involved in this study and the staff of the  Malaria Molecular Epidemiology Unit at the Institut Pasteur in Cambodia and of the National Center for Parasitology, Entomology and Malaria Control in Cambodia  for their collaboration and sample collection. We also thank  Alejandra Gonzalez-Tobon  for the sporozoite isolation. This work was funded by a  National Institutes of Health -NIAID  award to DS ( R01A103328 ). Additional support was provided by a  PTR award  from the  Institut Pasteur  to DM ( PTR 490 ). The sporozoite work was sponsored by  NIAID  grant  1U19AI089702.
As shown in the synthesis made by Picard-Meyer for the 2004-2009 period, the sampling of such programs involved blood and saliva samples from more than 300 bats on 18 sites  [41]. In such cross-sectional surveys, the bats were sampled on various sites throughout France and no data from marked individuals were available to allow a longitudinal study. This study proposes the first longitudinal survey of EBLV-1 in mono-specific serotine colonies, the main bat species found infected by this lyssavirus. Multi-state models, a category of capturerecapture analysis, have been used to attempt explaining EBLV-1 virus exposure. Originally developed for estimating the abundance of animal populations, capture-recapture methods have recently attracted attention in the field of veterinary epidemiology  [42, 43].
When appropriate data are available, capture-recapture models can also be used directly to estimate disease-associated mortality and epidemiological parameters, such as infection and recovery rates  [44]. In this study, as the serological status of individuals could change, data were analyzed using a multistate capture-recapture approach  [45]. Multistate models indeed allow individuals in a population to be distributed across multiple sites or among different disease states  [46, 47]. More precisely, we used multievent capture-recapture models  [48] , an extension of multistate models, to determine the factors influencing bat rabies transmission while accounting for imperfect detection and uncertainty in disease states. Survival, capture, transition and judgment probabilities were assessed by hypothesizing, based on lyssaviruses literature, that EBLV-1 exposure in bat maternity colony was driven differently according to the age of individuals and the period of time.
Field data collection Capture-recapture sessions were completed in summer (July and August) and spring (May) between 2009 and 2015 (during 7 years) for site A, and between 2011 and 2015 (during 5 Captures were held at nightfall, when serotine bats are known to leave their roost to forage. Harp traps were used because they are the most suitable device when a large number of animals can be expected  [52]. Moreover, these traps are considered the most effective for capturing bats without harming them  [53]. Traps were placed at the exits of the roof from where the bats usually emerged. To avoid injury, they were handled carefully and firmly by trained people wearing gloves and adequately vaccinated against rabies. As soon as the bats were removed from the traps, they were placed temporarily in cotton bags and then held in the palm of the hand with fingers curled around the body  [54].
To address this particular issue and to allow the use of such a dataset, an extension of the multistate capture-recapture framework was used. This extension is known as the multievent model  [47, 67]. When an individual is observed in the field, its status can still remain unknown or uncertain, e. g. sex status  [68] , reproductive status  [69]  but also epidemiological status  [42, 47]  and such a model accounts for uncertainties in the assessment of a state. The different probabilities assessed during the study were as follows: • Survival probability (ϕ): the probability that an individual (with "POS" or "NEG" status) remains alive over a given period of time. • Recapture probability (p): the probability that a living individual (with "POS" or "NEG" status) is encountered during a capture session.
• Transition probability (ψ): the probability that, over a given period of time, an individual "moves" from one serological state to another, i. e. from seronegative to seropositive status ("NEG" to "POS") or from seropositive to seronegative status ("POS" to "NEG"), or remains in its current state. • Judgment probability (δ): the probability that an "INC" status individual had a seropositive ("POS") or seronegative ("NEG") status. The models were fitted using the E-SURGE program  [70]. Both sites were maternity colonies mainly composed of females with roost site fidelity and juvenile males leaving the colony at the end of their first summer  [71] , males were consequently discarded from the dataset to avoid bias in the survival analysis. Multiple capture sessions were conducted occasionally within the same season (between 2 and 5), and the detection/non-detection data were merged into a single capture session per year and season.
The year "y" and/or season "s" (spring/summer) effects and their interaction were considered with regard to recapture probabilities as weather variations are suspected to impact trapping efficiency. Possible interactions with the serological status were also assessed to determine whether there were any specific infection patterns. All model combinations to estimate survival, transition, capture and judgment probabilities fit accordingly. Akaike's Information Criterion with a correction for small sample sizes (AICc) was used to assess the relative model fit. The model with the lowest AICc was selected as the model that fitted the data best  [75]. When the ΔAICc was lower than 2 (Δi = difference between AICc and the lowest AICc value), the most parsimonious model was selected (i. e. the one with the fewest variables).
Of the 5 positive samples, one was demonstrated as effectively infectious, showing that RNA in the mouth cavity can be concomitant to virus excretion. One initially seronegative animal was captured several times in succession. Saliva was found RNA positive 3 days later and, when captured again 1 year later, the animal was again found seropositive, supporting the hypothesis that seropositivity persists for a long time after infection or that alternate subclinical infection occurred. The risk of cross-contamination regarding the four RNA positive samples collected during the same capture session can't be completely ruled out with certainty although usual precautions to avoid false-positive PCR results were strictly followed during bat handling and in the laboratory. However, the raw-data of this capture shown that the RT-PCR positive swabs were collected and analyzed intercalated with RT-PCR negative swabs, suggesting that laboratory cross-contamination is unlikely.
Acknowledgments We would like to thank all the people directly or indirectly involved in this extensive work. We acknowledge the skilled technical support provided by the serology team ( Anouck Labadie ,  Laetitia Tribout , and  Jonathan Rieder ), the molecular biology team ( Melanie Biarnais  and  Jean-Luc Schereffer ) and the field team ( Jean-Michel Demerson  and  Christophe Caillot) of the Nancy Laboratory for Rabies and Wildlife. We are also grateful to all the volunteers of the CPEPESC Lorraine. Our special thanks go to the house owners who allowed regular access to their property. We are also grateful to  ANSES , the  French Ministry of Agriculture's Directorate General for Food (DGAL) , and to the  French Ministry of the Environment  for their support.
Sequencing and bioinformatics analysis All samples' alignment ranged from 85%-98%. Almost 98% of the target at 1X depth was covered for all samples and more than 85% of the target was covered at 30X depth. Exome data was uploaded to the NIH Short Read Archive repository (https://www. ncbi. nlm. nih. gov/sra) (BioProject accession number: PRJNA325830; Short Read Archive-SRA accession number: SRP114508). RPL-234 data analysis revealed 15944 sequence variants (Fig  1 ). 249 of these were novel (24685 when all the genes/exons were considered throughout the genome). One splice-site variant was found which was not confirmed by direct sequencing (false positive). Among novel RPL-234, 128 variants (51%) induced a protein change while 7839 (31. 7%) affected the rest of the genome (All-Ex). The statistical comparative analysis of these proportions revealed that the RPL-234 list is strongly enriched by this kind of variants (128 variants observed with 99 expected, p = 0.
After 48 h of incubation, CFSE-labeled RL cells were resuspended in DAPI (2 μg/ml) followed by flow cytometric analysis. Cell death (E) and cell proliferation (F) were measured using DAPI and CFSE assays, respectively. Data are expressed as mean ± SD of three independent experiments. (G-H) CFSE-labeled RL cells were cultured in the presence of 10 nM VCR in a complete RPMI medium, or with conditioned mediumfor 48 h. then CFSE-labeled RL cells were resuspended in DAPI (2 μg/ml) followed by flow cytometric analysis. Cell death (G) and cell proliferation (H) were measured using DAPI and CFSE assays, respectively. Data are expressed as mean ± SD of one experiment performed in triplicate. One-way ANOVA statistical test was used for multiple comparisons applying Holm-Sidak method. **p≤ 0. 01, ***p≤ 0.
Mcl-1 upregulation via IL6/Jak/Stat pathway Our data indicated that RL cells, by direct contact with neutrophils, induced the latter to undergo activation as determined by the increase in the expression of several activation markers (Supplementary Table  1 ). We examined whether activated neutrophils in our co-culture conditions release IL6 cytokine that may have a direct effect on Mcl-1 induction through the activation of the Jak/Stat pathway as previously described  [35]. IL6 concentrations were quantified in the supernatant of our different culture conditions using ELISA and were detectable (0. 32 pg/ ml) only when RL cells were exposed to vincristine in the presence of neutrophils. Then we detected the phosphorylation level of Stat-3 in RL cells using flow cytometry at different times.
Cell proliferation of CD19 positive population was measured using CFSE assay followed by flow cytometric analysis. Data are expressed as mean ± SD of at least four independent experiments performed in triplicates. The data are presented relative to the control. (B) CFSE-labeled RL cells were cultured alone or together with neutrophils in the presence or absence of CD44 blocking antibody (1 μg/ml) treated with 10 nM VCR. Cell proliferation of CD19 positive population was measured using CFSE assay followed by flow cytometric analysis. Data are expressed as mean ± SD of three independent experiments performed in triplicates. The data are presented relative to the control. (C) Relative expression of Bcl-2 family members (Bcl-xL, Bcl-2, Mcl-1) in RL cells. RL cells were cultured alone or together with neutrophils at N:T ratio 10:1, in the presence or absence of 10 nM VCR.
After 48 hours of incubation, the cells were collected and labeled with anti-human CD19 thenfixed and permeabilized. Later, the intracellular labeling of anti-apoptotic Bcl-2 family members was performed by flow cytometry. Data are expressed as mean ± SD of at least three independent experiments performed in triplicates. (D) RL cells were cultured alone or together with neutrophils at N:T ratio 10:1, in the presence or absence of 10 nM VCR. ABT-199 (10 nM) or MIM-1(10 μM) inhibitors were added to the culture system. After 48 h of incubation, cells were labeled with anti human-CD19 then resuspended in DAPI (2 μg/ml) followed by flow cytometric analysis. Cell death of CD19 positive population was measured using DAPI assay. Data are expressed as mean ± SD of three independent experiments performed in triplicates.
Tumor cells have previously been shown to influence the phenotype and properties of cells present in their microenvironment, in particular through the polarization of tumor infiltrating neutrophils  [10, 41]. In our study, exposure to cytotoxic chemotherapy did not modify the expression levels of activation markers of neutrophils such as CD11a, CD11b, CD18, CD32 and CD66b, while EDTA and cells were labeled with anti-human CD19 and anti-human CD38. The number of events in CD19+ Annexin V-/PI-population was measured by double staining with annexin V-FITC and PI, followed by flow cytometric analysis. Data are expressed as mean ± SD of three independent experiments performed in triplicates. One-way ANOVA statistical test was used for multiple comparisons applying Holm-Sidak method. **p≤ 0. 01    (E-F ) CLL cells were co-cultured with autologous neutrophils at different N:CLL ratios for 24 h, in the presence or absence of (E) 25 μM Ibrutinib (10 patients) or (F) 50 μM Idelalisib (10 patients).
Flow cytometric analysis of surface antigens-Cells were collected and washed in PBS with 4% FBS. Cells were incubated with fluorochrome-conjugated purified monoclonal antibodies at 4 0 C for 30 minutes. Later, cells were washed with PBS-4% FBS and the relative levels of surface antigens were assessed by FACS analysis on LSRII (BD Biosciences (San Jose, CA, USA)) using FACS Diva or Flowjo softwares.
Expression microarray studies RL cells were cultured alone or together with neutrophils at a N:T ratio of 10:1, in the presence or absence of 10 nM vincristine for 2 hours at 37 0 C. RL cells were negatively purified (≥ 90 % pure) after labeling the cells with anti-human CD15-Biotin (Miltenyi Biotec) then anti-Biotin Microbeads (Miltenyi Biotec) followed by magnetic column separation (LD Columns, Miltenyi Biotec). RNA was extracted using Qiamp RNeasy mini kit (Qiagen). After RNA amplification with total prep RNA amplification kit (Ambion), cRNA was hybridized on human HT-12 v4 beadchip (Illumina). Chips were scanned with an Illumina iScan and data was analyzed using GeneSpring and Ingenuity softwares. Microarray data have been deposited in the GEO database under accession number GSE69255.
Analysis of patient samples and clinical data To determine the clinical relevance of our findings in patients with lymphoid malignancies, we analyzed two models: the protective effect of autologous neutrophils on CLL cells ex vivo, and the correlation between peripheral neutrophils counts and patient outcome in patients with follicular lymphoma. Peripheral blood on EDTA was obtained from patients (aged 58-90 years) diagnosed with CLL according to standard criteria. Procedures were conducted under the approval of Lyon Hospital Ethics committee with all patients signing informed consent. CLL cells were isolated by Ficoll density-gradient centrifugation and purity was verified by CD19 labeling (≥ 90% CD19positive). CLL cells (2x10 5 cells/mL) were cultured alone or with autologous neutrophils, isolated as described above, at different N:CLL ratios.
Chemotherapeutic agents (vincristine and fludarabine) or targeted therapies (ibrutinib and idelalisib) were added to the cultures. After 24 hours, the percentage of viable CLL cells (Annexin V negative/PI negative) was determined by double staining of the cells with Annexin V-FITC/PI. Correlations between neutrophil blood counts at diagnosis and clinical outcome in patients with follicular lymphoma were determined on a retrospective series of 367 consecutive patients receiving their first line treatment in the Hematology Department of the Hospices Civils de Lyon. Initial and follow-up data were collected from routine hospital charts according to French Ethics Requirements.
Statistics Flow cytometry data were analyzed using BD FACSDiva™ software and FlowJo, LLC data analysis software. The sample size (n) for each experimental group/ condition represent biological replicates and indicated in each figure legend. Results were expressed as the mean ± SD of at least three independent experiments, each performed in triplicates. One Way Anova test (Sigma Plot ® , Systat Software) and Student's t test were used for comparison among groups, and p-values were reported. Some experiments were performed once in triplicate. For in vivo experiments, results were expressed as median ± S. E. M. Response to treatment according to international response criteria  [47]  were compared using the Chi2 test. Comparison of overall survival data of patients were assessed using the Log-Rank test.
(E-F) CFSE-labeled RL cells and neutrophils were co-cultured on opposite sides of porous PET inserts. Neutrophils (N) were placed inside the inserts whereas CFSE-labeled RL cells were placed in the wells, or to inserts with complete RPMI medium as a control. VCR at 10 nM was incorporated at the initiation of culture on CFSE-labeled RL cells. After 48 h of incubation, CFSE-labeled RL cells were resuspended in DAPI (2 μg/ml) followed by flow cytometric analysis. Cell death (E) and cell proliferation (F) were measured using DAPI and CFSE assays, respectively. Data are expressed as mean ± SD of three independent experiments. (G-H) CFSE-labeled RL cells were cultured in the presence of 10 nM VCR in a complete RPMI medium, or with conditioned mediumfor 48 h. then CFSE-labeled RL cells were resuspended in DAPI (2 μg/ml) followed by flow cytometric analysis.
Safety and tolerance evaluation Safety and tolerance of L-AmB in patients with ICU-acquired severe sepsis were assessed by recording the incidence of related adverse events occurring during the 28-days study period. Other safety data (biological parameters, vital signs. ) were also described in the analysis. Adverse events were tabulated according to "Preferred Term" and "System Organ Class" using the MedDRA classification version 11. 0. Tables presented the number of patients with adverse events as well as the frequency of adverse events.
Other outcomes Candida colonization (lung, gastrointestinal tract, urine, mouth, pharynx and anus as well as the injury, wound or drain) was assessed at day 1 and then twice a week. Data on the use of antifungal agents were collected and invasive fungal infections according to the EORTC/MSG criteria were reported. Vital signs and SOFA score  [28]  were collected at day 1, 2, 3, 8, 14, 21 and 28 or at the end of the study. Morbidity criteria defined as length of ICU and hospital stay, and survival were also collected.
The phenyl-sulfonamide moiety of compound 1 displays additional hydrophobic interactions with an extension of the SPD304 binding pocket surrounded by L129, L43, L270, I268 and I127. This binding mode of compound 1, compared to the binding mode of SPD304, would not only hinder the positioning of the side chain of Y119 of the disrupted TNFα monomer  17  but also the side chains of L57, L157 and V123 of the disrupted TNFα monomer. To illustrate the alternate binding mode of compound 1 on TNFα, we explored the whole surface of the structure of human trimeric TNFα (PDB ID: 1TNF) to identify an additional binding pocket at the surface of the homotrimer that contains tryptophan residues (Fig. 3b ). After a careful visual inspection, a pocket has been identified at the junction of the three TNFα subunits that is conserved in the homodimeric structure cocristallized with SPD304 (PDB ID: 2AZ5).
HEK-Blue ™ TNFα reporter cell line and QUANTI-Blue ™ were obtained from InvivoGen (Toulouse, France). 7 weeks-old female Balb/C mice were obtained from Charles River Laboratories (L' Arbresle, France). Mice used in all experiments were handled according to the guidelines and protocols were approved by the ethical commitee of Paris Descartes University, France. In silico screening. Structure preparation. The binding site has been defined at 4 Å around the co-crystallized SPD304 ligand in the structure of the TNFα dimer (PDB id: 2AZ5, Supplementary Fig. 1 ). Hydrogen atoms were added using Chimera  38. Compound collection. The 900,000 compounds Chembridge screening compound collection was retrieved from www. hit2lead. com. After an ADME-tox filtering using FAF-drugs2  39  , 700,000 compounds were selected to constitute our commercially available drug-like compound collection.