dataesr/scientific-paragraphs-categorization huggingface dataset:
00 0. 73 4. 00 15. 58 1. 87 Vinograd [34] SAD-B19 1. 55 0. 82 1. 63 17. 19 0. 00 Wee [15] SAD-B19 2. 72 0. 00 5. 62 17. 55 1. 99 Allen Institute [35] CVS-N2c 7. 16 0. 00 17. 17 14. 32 3. 58 this dataset CVS-N2c 0. 00 15. 99 Beier SAD-B19 0. 00 13. 47 Brown SAD-B19 0. 00 11. 97 Fu SAD-B19 0. 00 14. 18 Gehrlach SAD-B19 0. 00 15. 93 Graham interneuron CVS-N2c 0. 00 15. 25 Graham projection CVS-N2c 0. 00 16. 23 Hafner SAD-B19 0. 00 17. 55 Kim SAD-B19 0. 00 13. 43 Pouchelon-P30-P42 CVS-N2c 0. 00 16. 03 Pouchelon-P5-P10 CVS-N2c 0. 00 16. 15 Sun SAD-B19 0. 00 12. 90 Takatoh SAD-B19 0. 00 16. 34 Vinograd SAD-B19 0. 00 16. 28 Wee SAD-B19 0. 00 15. 70 Allen Institute CVS-N2c 0. 00 16. 15 https://doi. org/10. 1371/journal. pone. 0278053. t001 https://doi. org/10. 1371/journal. pone. 0278053. t002.
Electron microscopy For scanning and transmission electron microscopy, PBMCs were cultured in 6-well plates and collected 24 h after infection with T. gondii tachyzoites at MOI = 1. Adherent cells were collected using a scraper, washed in 1x PBS and fixed in 0. 1 M phosphate buffer (pH 7. 2) containing 4% paraformaldehyde and 1% glutaraldehyde. Cells were fully dehydrated in a graded series of ethanol baths (50°À 70°À 90°À 100°). For the scanning electron microscopy, a polymerization step preceded the sectioning of samples with a microtome. Observation and data were obtained thanks to the assistance of the IBiSA Electron Microscopy Facility (University of Tours, France).
Statistical analysis GraphPad Prism Ò software (version 7. 05) was used for data analysis. Based on distribution, tested using Shapiro-Wilk test, nonparametric tests (Wilcoxon, Mann-Whitney or Kruskal-Wallis followed by a Dunn's multiple comparisons test) or parametric paired t-test were performed. All statistical tests were two-sided and a value of P < 0. 05 was considered statistically significant.
DGNP/TE vaccine induces mild humoral immune response Squirrel monkeys were first vaccinated by the nasal route to induce mucosal and systemic immune responses. To assess the mucosal humoral immune response, presence of IgA and IgG was explored by endpoint ELISA in faeces of squirrel monkeys before and after vaccination at day 0 and 6, 12, and 24 months after vaccination. Irrespective of time or status (before vaccination, vaccinated or infected), no IgA or IgG was detected in the faeces of saimiris (data not shown). Systemic humoral immune responses were explored in sera of squirrel monkeys. Serum IgA and IgG were analysed by endpoint ELISA before and 6, 12, and 24 months after vaccination compared with infected subjects (Fig. 2 ). Among the few squirrel monkeys showing a weak IgA titre (>day 0 titre) after vaccination, only three subjects had an IgA titre of 400 at 1 year after the full protocol.
A similar cell mortality was observed in each group: 15-20% with TLRs antagonists and 9-19% with NLRs antagonists (data not shown). Regarding T. gondii recognition by TLRs, their functionality was assessed by secretion of TNF-a, IL-1b and IL-6. Fig. 5  shows the IL-6 secreted by squirrel monkeys' PBMCs in response to T. gondii stimulation, both with TE (median = 120. 3 pg/mL [95. 24-159]) and live RH tachyzoites (median = 272. 5 pg/mL [166. 5-327. 8]). A significant decrease in IL-6 was observed when specific TLRs antagonists (see Supplementary Table  S2 ) were added (Fig. 5B-H ), except for TE-stimulated PBMCs in the presence of TLR1/2 antagonist (Fig. 5A ). IL-6 secretion decreased when PBMCs were stimulated by TE and live RH parasites respectively to 90. 17 and 243 pg/mL in the presence of antagonist for TLR4 (Fig.
5C, D ); to 105. 1 and 187. 9 pg/mL for TLR8 antagonist (Fig. 5E, F ) and to 94. 57 and 187. 8 pg/mL for TLR9 antagonist (Fig. 5G, H ). The same tendency was observed with related enriched APCs but this was not significant (data not shown). For TNF-a and IL-1b measurement, no difference was observed (50 pg/mL and 20 pg/mL respectively) irrespective of the cell stimulation conditions i. e. no stimulation versus TE or RH +/-antagonists (data not shown). Toxoplasma gondii recognition by NLRs was assessed by measuring IL-1b secreted by PBMCs or related enriched APCs in response to live RH T. gondii in presence of specific antagonists of NLRP3 and caspase-1. As shown in Fig. 6A , a high but not significative increase of IL-1b was noted 82. 66 pg/mL  [39. 18-117. 8 ] 4 h p. i. compared with cells alone  (44.
Humoral and cellular immune responses induced by the vaccination were followed throughout the immunisation process. Although data recording was performed on animals of different sex and from different zoos, no difference in immune responses was observed also suggesting there was no impact of diet, enrichment and/or husbandry which allowed to subjects to be considered as one group. The immune response was recorded only for adults (8+/-6 years) since  Nehete et al. , (2013)  demonstrated that specific differences exist in immune function of lymphocytes between young (3-4 years), adult (8-10 years) and old (16-19 years) squirrel monkeys. Due to field conditions, samples of few animals could not be collected each time and the blood samples could only be performed at times of medical procedures.
, 2017). We used a specific NLRP3 inhibitor MCC950 that directly binds to the ATPase domain of the protein and that was described in mouse and human macrophages, to block NLRP3 inflammasome activation and IL-1b production  (Zahid et al. , 2019). NLRP3 protein sequence of Saimiri boliviensis boliviensis has been added recently in GenBank (XP_010344136. 1). Our results are consistent with the data obtained in mouse and human and we demonstrated a reduced release of IL-1b in T. gondii infected-PBMCs treated with this NLRP3 inhibitor. Consistent with the results in human and mouse, we did not observe cell pyroptosis after infection. A cell-permeable, selective and irreversible inhibitor of caspase-1 induced significant inhibition but at a similar level as observed with the NLRP3 inhibitor in our culture conditions.
Acknowledgments We are grateful to all the partner zoos who have trusted us to take their animals into the vaccine protocol to face potential fatal toxoplasmosis and thank them for all their contributions. We want to thank  Champrépus Zoo  (DVM  Delphine Macquet  and  Mr Lebreton ),  La Palmyre Zoo  ( DVM Thierry Petit ),  Beauval Zoo  (DVM Baptiste Mulot and DVM  Antoine Leclerc ) and  La Flèche Zoo  ( DVM Margot Chandenier ) for their guidance and enlightening discussions. We are grateful to  Dr L. Lantier  for English proofreading. Thanks to  Virginia GIROD-DAVID ,  Pau Molina Vila  and  Romain Lacoste  from the primatology station, CNRS  UPS846 ,  Le Rousset ,  FRANCE. We want to thank  Sonia Georgeault  for the electronic microscopy data acquisition and analysis obtained at  IBiSA Electron Microscopy Facility of the University of Tours , France as well as  Julia Salazar-Gustavsson  and  Charlotte Benard  for the providing of Mabtech ELISA test samples.
This study was granted by  Vaxinano SAS , Lille, France and was supported by the  Ministry of Higher Education, Research and Innovation  in the context of the CIFRE PhD thesis n°2018/1860 of PC funded by [include explanation of abbreviation and country] (ANRT). DB is founder,  CEO  and  CSO of Vaxinano , SAS, CH and PC are employees of VAXINANO. Other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments We thank all actively contributing members of the  ECNM  and the  AIM  for their contributions in this project. The ECNM and AIM members who provided significant contribution to the discussion and the preparation of the proposals in this manuscript are listed as coauthors on this document. All authors contributed equally by discussing the available literature, by providing unpublished data, and/or by providing and discussing case reports. All authors contributed substantially by writing and/or extensively reviewing parts of the manuscript. All authors approved the final version of the document.
Data collected and study period Sentinelles network uses case definition proposed by the study group for Lyme borreliosis (ESGBOR)  [12] , which includes EM. Cases with suspected EM less than five centimeters in size are included in the definition, except when a tick bite and a delay of less than two days between the date of the bite and the date of diagnosis are mentioned. For each LB case reported by a SGP, data are collected from a standardized questionnaire to describe the clinical manifestations, including the presence of an erythema migrans, its size (in centimeters) and expanding nature, aspect, number of lesions, presence of other clinical manifestations, blood serological test prescription for this episode as well as the history of tick bites preceding the symptoms. Basic characteristics of the patients such as age and sex are also collected.
Analysis We described the LB cases and characteristics of the SGPs who reported the cases. The proportion of EM episodes for which a LB serology was prescribed was calculated by year over the study period and the trend was evaluated with Cochran-Armitage tests. To assess the association between each factor and serological test prescription, we subsequently conducted a descriptive analysis and a series of bivariate multilevel logistic regression models. Multilevel models were used to take into account the hierarchical structure of our data (episodes within SGPs) and the non-independence of observations within SGPs. In our final model, adjusted odds ratios and their 95% confidence intervals were estimated using a multivariable multilevel logistic regression model. Since information on EM size and its expanding nature was not collected in 2009 and 2010, the analysis of factors associated with the prescription of a LB serological test has been limited to cases reported from 2011 onwards.
Ethics approval and consent to participate The protocol was conducted in agreement with the Helsinki declaration. Ethical approval was obtained from the French Data Protection Agency (CNIL #471393) and the French ethical research committee (Comité de protection des personnes -CPP). The French Sentinelles Network database is built and used in accordance with French legislation on health data collection and treatment. It contains pseudonymized data of the patients of the general practitioners participating in the network, except for those patients who object. This study is therefore exempt from informed consent by each patient. This research work was conducted by members of the Sentinel Network team, so no special request was needed to access the database.
For each picture, cells were defined and for each cell the total fluorescence intensity of lumogallion and LysoTracker was calculating by addition of pixel intensity and normalized by cell surface to obtain mean intensity fluorescence per µm 2. The degree of colocalization between fluorophores was calculated with Colocalization Studio package of Icy Software by pixel based evaluation of the Pearson correlation coefficient. Western blots. After the week of pre-treatment on 24 wells culture plate, differentiated PBMCs were exposed 4 h to vehicle (PBS), or to AH diluted to a final concentration of 50 µg Al/ml or to a whole vaccine (Engerix ® 20, GSK) adjuvanted on AH (500 µg AL/ml) with the appropriate dilution to obtain the same final concentration of 50 µg Al/ml. Positive and negative controls were obtained by using autophagy modulators that were respectively Rapamycin (Rapa) at 100 nM or Chloroquine (CQ) at 100 µM.
Protein bands were quantified by ImageJ© software (V1. 53i, Wayne Rasband and contributors, National Institute of Health, USA)  63  and normalized to β-actin, which served as an internal control. Autophagic function was assessed via changes in the expression of commonly used proteins (LC3, p62) and LAP function via specific components (Rubicon, NOX2). LC3 and especially LC3-II and SQSTM1/p62 are generally associated to autophagosomal membrane and used as marker of this cellular compartment presence. LC3-II/LC3-I ratio is usually a good indicator of autophagy activation state  35. Cytokines assay. The same cell cultures performed for western blot were used for cytokines assay. After 4 h of treatment (described previously in the western blot section), the culture medium was used to perform a semi-quantification of an 11 excreted cytokines panel: interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-18, CXCL1, CCL2, CCL4, TGFβ, and TNF-α.
Positive controls were obtained by H 2 O 2 treatment 45 min at 500 µM before data collection. ROS were stained by addition of H 2 DCFDA 45 min at 5 µM simultaneously with positive controls. Results were visualized using a fluorescent plate reader allowing fluorescence readings at 530 nm after excitation at 485 nm along a matrix of 5 × 5 on each wells surface. After data recording, cells were lysed in 100 µl of 95 °C TR3 solution then the total amount of protein was measured using a BCA protein assay kit. Fluorescence of H 2 DCFDA was finally normalized by the total amount of proteins of each well. Mitochondrial metabolism evaluation. Differentiated PBMCs were exposed 4 h to AH or to the vaccine diluted at the same final concentration of 50 µg Al/ml. After Al treatments, cells were washed and kept in seahorse buffer along the measurement.
Acknowledgements This research is supported financially by  Agence Nationale pour la Recherche (ANR)  and  I For Lyme. Authors also acknowledge  Entraide aux Malades de Myofasciite à Macrophages  ( E3M ) and, BioSanté editions for their supports. Dr M. -O. David  and  Mr L. Angrand  are acknowledged for scientific discussion, advice for redaction and careful proofreading.
Genomic data and maximum likelihood tree generation All available MPXV sequences were downloaded from GenBank while excluding sequences from countries with five or fewer sequences, leaving Austria, Belgium, Canada, Colombia, France, Germany, Italy, Peru, Portugal, Slovakia, Slovenia, Spain, Switzerland, United Kingdom, and the USA. Sequences with ambiguous dates in the month column, with a sample collection earlier than January 2022, and flagged as being low quality by Nextclade  (17)  were excluded. Given that the 2022 epidemic was found to be driven by MPXV clade II, lineage B  (14, 18) , any sequences not part of lineage B were also excluded, resulting in 3013 genome sequences included in our analysis. A temporally-resolved phylogeny was created using a modified version of the Nextstrain  (19)  monkeypox workflow (https://github.
com/nextstrain/monkeypox), which aligns sequences against the MPXV_USA_2021_MD (accession ON918611) reference using nextalign  (17) , infers a maximum-likelihood phylogeny using IQ-TREE  (20)  with a GTR nucleotide substitution model, and estimates molecular clock branch lengths using TreeTime  (21). The resulting phylogeny specific to this dataset can be found at https://nextstrain. org/groups/blab/monkeypox/hmpxv1.
Data Sources Data on the number of reported mpox cases per region per month were downloaded from OWID (https://ourworldindata. org/; last accessed on February 13 2023). Population sizes for each country were downloaded from the World Bank (https://data. worldbank. org/indicator/SP. POP. TOTL) and aggregated based on respective countries and then regions as described in the previous section. To compare vaccination rates with changes in Rt, we accessed publicly available vaccination counts from the CDC (https://www. cdc. gov/poxvirus/mpox/response/2022/vaccines_data. html) as well as the cumulative percentage of high risk individuals vaccinated  (22). In order to account for the development of immunity, we followed the CDC method of assuming the development of immunity took two weeks following vaccination (22).
Estimated importation intensity We estimated the monthly importation intensity of mpox between the five selected global regions between May and December 2022 using air travel data, estimated regional prevalence and regional human population size. The monthly estimated importation intensity (EII) is an estimate of the number of mpox cases imported into each region during a given month, calculated as , 𝐸𝐼𝐼 𝑎 (𝑡) = 𝑖 !=𝑎 ∑ 𝑃 𝑖 (𝑡) 𝑇 𝑖 × 𝑛 𝑖 →𝑎 (𝑡) where (EII for region a at month t is computed using the estimated mpox prevalence in a 𝑃 traveling from region i to region a (adapted from Fauver et al. (33) ). The sum over every global region excluding domestic travel. We used the prevalence estimates obtained from case data as described in the previous paragraph.
MASCOT GLM To analyze the transmission dynamics within and between each global region, we used an adapted version of MASCOT  (34). MASCOT is an approximate structured coalescent approach (35) that models how lineages coalesce (share a common ancestor) within the same locations and migrate between locations. We used generalized log-linear models  (36)  to estimate whether estimated regional mpox prevalence and air passenger volumes are predictive of MPXV effective population sizes and migration rates over time, respectively. Additionally, in order to account for differential underreporting by month, ten additional effective population size predictors were added, one for every month of the time period studied from April 2022 through January 2023. Empirical predictors were obtained via data sources described above.
The model included error terms to account for observation noise and omitted predictor variables. We implemented a MASCOT-GLM  (36)  analysis with BEAST2 (37) software, allowing the effective population sizes and the migration rates to change every week. We performed effective population size and migration rate inference using an adaptive multivariate Gaussian operator  (38)  and ran the analyses using an adaptive Metropolis-coupled MCMC (39) using four chains with a length of. For this analysis, we employed equal temporal subsampling to enrich for 2. 5 × 10 8 undersampled regions by randomly choosing a max of 11 sequences per region per calendar month via Augur filter  (40) , resulting in 587 included sequences. No alignment masking was conducted for MASCOT analyses.
Early mpox spread in Western Europe sparks prolonged outbreaks in Southern Europe, North America and South America Following initial detection in the UK on May 7, 2022, the number of mpox cases reported worldwide grew rapidly (Fig. 1 ). In early May, reported cases were found mainly in Western and Southern, and then Central, Europe where the epidemic peaked around mid-July (Fig 1A  , B ). Beginning in mid-May, however, cases began to be reported in North America, which ultimately led to the largest number of reported cases of any global region studied, peaking at the beginning of August. Around the same time as the North American peak, cases were detected and started rising in South America, which substantially contributed to the later tail of the 2022 mpox epidemic. Similarly, the number of sequences collected increased as more cases were detected, with heterogeneity between regions and North America ( primarily the US) submitting the largest number of sequences to GenBank.
Rapid early spread characterized by significant underdetection of cases In order to analyze within-region transmission dynamics, improve robustness to sampling bias, and enhance inference via the joint integration of genomic and epidemiological metadata, we then employed an approximate structured coalescent (MASCOT) with a generalized linear model (GLM) approach with estimated prevalence and air passenger data as empirical predictors on 587 sequences (Supp. Fig 3). We also included a predictor for each month within the time period studied to account for potential changes in case detection over time. The included sequences were subsampled with equal temporal weighting to increase representation of undersampled regions such as Central Europe (Supp Fig. 1 ). The MASCOT-GLM subsampling scheme is different from the subsampling for the DTA analysis as the structured coalescent is more robust to differences in sampling across regions and is subsequently informed by regional prevalence  (49, 50).
Together, these findings highlight the significant effect of behavioral change among men who have sex with men and other high-risk communities in curbing the epidemic as well as push for a prompt public health response that includes early vaccination campaigns in order to maximize the population-level effectiveness of vaccines. Our study has noteworthy limitations. Our genomic data only cover a small selection of countries and regions, suggesting that we are missing transmission events that involve unsampled countries, especially from regions such as Asia, Oceania, and Africa. Additionally, the changing availability of genomic sequencing, as well as unequal sampling across the regions study affect the probability that a case shows up as a sequence in our dataset through the period studied.
Funding MIP and MF are ARCS Foundation scholars. MF was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE1762114. T. B. is a Howard Hughes Medical Institute Investigator. This work was supported by NIH NIGMS award R35 GM119774 to T. B. Analyses were completed using Fred Hutch Scientific Computing resources (NIH grants S10-OD-020069 and S10-OD-028685).
Introduction: As part of the EU Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections, an initiative has been launched to build the European AMR Surveillance network in veterinary medicine (EARS-Vet). So far, activities included mapping national systems for AMR surveillance in animal bacterial pathogens, and defining the EARS-Vet objectives, scope, and standards. Drawing on these milestones, this study aimed to pilot test EARS-Vet surveillance, namely to (i) assess available data, (ii) perform cross-country analyses, and (iii) identify potential challenges and develop recommendations to improve future data collection and analysis. Methods: Eleven partners from nine EU/EEA countries participated and shared available data for the period 2016-2020, representing a total of 140,110 bacterial isolates and 1,302,389 entries (isolate-antibiotic agent combinations).
, 2022a). Drawing on the EARS-Vet milestones achieved so far, the objective of this study was to pilot test surveillance by EARS-Vet. Specifically, we aimed to (i) assess available data from partner countries, (ii) perform cross-country analyses for selected bacteriaantibiotic combinations, (iii) identify potential challenges, and (iv) formulate recommendations for future improvement of EARS-Vet data collection and analysis.
Data sources Upon signature of a data sharing agreement, 11 partners from nine European countries participated in the EARS-Vet pilot study and shared their available data for the years 2016 to 2020. The majority of partners retrieved data from national monitoring systems of AMR in bacterial isolates from diseased animals, the structures and operations of which have been described previously  (Mader et al. , 2022b). Additional data on companion animals were retrieved in Germany from LABOKLIN GmbH & Co KG, a large private veterinary diagnostic laboratory providing services in the whole country, and in Italy from a large veterinary referral hospital (AniCura Istituto Veterinario Novara) receiving animal patients from Northern Italy and subcontracting bacteriology testing to a private clinical laboratory (Idexx).