dataesr/scientific-paragraphs-categorization huggingface dataset:
For data analysis, a first logical gate was based on side scatter and CD45 intensity, followed by a second gate on the patient-specific LAIP to identify leukemia cells and on CD3 for T cells. At least 200,000 events in the live cells gate were acquired per sample. Analysis of human samples was performed using a Canto II flow cytometer equipped with 405, 488 and 633 nm lasers, or using a LSR Fortessa flow cytometer equipped with 355 nm, 405, 488, 561 and 640 nm lasers (both from BD Biosciences). Analysis of mouse samples was performed using a Gallios flow cytometer equipped with 488, 638 and 405 nm lasers (Beckman Coulter). Each acquisition was calibrated using Rainbow Calibration Particles (Spherotech) to correct for day-to-day laser intensity variations. Data were processed using FCS 4 Express (De Novo Software), FlowJo v.
9. 8. 5 (Tree Star) or Kaluza (Beckman Coulter). Representative plots with gating strategy and controls are shown in Supplementary Figs. 1  and 2. Differences in percentages were used to calculate sample clustering, using correlation coefficient as distance measure and Ward's method for agglomerative clustering. An ANOVA F-value was used to rank the relative influence of each marker in determining clusters. Heatmaps were elaborated using the pheatmap package  50. High-dimensional analysis of flow cytometry data from the entire validation sample cohort (72 samples, 36 from diagnoses and 36 from relapses) was performed using the Barnes-Hut-stochastic neighbor embedding (BH-SNE) dimensionality reduction algorithm downscaling each sample to 5,000 CD3 - events. BH-SNE was visualized on MATLAB (MathWorks, Inc.
Human Th1 cytokines (IL-2, IL-6, IL-10, IFN-γ and TNF-α) were quantified in murine sera using Human LegendPlex 5-plex (BioLegend) according to the manufacturer's instructions. For each time-point and each experimental condition the sera of three biological replicates were analyzed. For each studied cytokine, a high-sensitivity standard curve was generated by serial dilutions of recombinant proteins. Data were analyzed using LEGENDplex v. 7. 0 (BioLegend). Leukemia blasts in vitro culture. Leukemia blasts were cultured in X-Vivo 15, 5% HS, 1% P/S, 1% G for 1 week in the presence or absence of human recombinant cytokines: IFN-γ (10 ng μl -1 ), TNF-α (5 ng μl -1 ), IFN-α (5 ng μl -1 ), IL-10 (10 ng μl -1 ) and IL-6 (10 ng μl -1 ). At 3 and 7 days after stimulation, cell surface expression of HLA class I, HLA-DR and -DP was analyzed on the leukemia blast population identified as described above.
In case of not-normally distributed data, the Wilcoxon matched-pair signed rank test at 95% CI was used. A P < 0. 05 was set as threshold for significance. If more than two groups were tested, a one-way ANOVA test with the Bonferroni correction was used. All statistical analyses were carried out using the GraphPad Prism v. 7. 0a software. Animal numbers were chosen according to the variability observed in pilot experiments and on the basis of leukemia cell availability. In all in vivo experiments, at least three biological replicates per group were tested. Regression analysis between relapse modalities and known clinical variables was performed through a univariate model, calculating for each variable of interest the odds ratio with the associated 95% CI. Reporting Summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Acknowledgements This work was supported by the  Italian Ministry of Health  (no. RF-FSR-2008-1202648  to K. F. , F. C. and  C. Barlassina , no. RF-2011-02351998  to F. C. and L. V. , no. RF-2011-02348034  to L. V. and  TRANSCAN HLALOSS  to L. V. and K. F. ), by the  Italian Ministry of University and Research  (no. MIUR-2015NZWSEC-001  to C. Bonini), by the  CARIPLO Foundation  (no. 2009-2665  to K. F. , A. R. and  C. Barlassina ), by the  Associazione Italiana per la Ricerca sul Cancro  (IG no. 18458  to C. Bonini, IG no. 12042 to K. F. and F. C. and Start-Up Grant no. 14162  to L. V. ), by the  ASCO Conquer Cancer Foundation  ( 2014 Young Investigator Award  to L. V. ),  EU- FP7  ( SUPERSIST  to  C. Bonini ), the  Deutsche José Carreras Leukämie Stiftung  (grant nos. DJCLS R 15-02  and  DJCLS 01 R/2017  to K.
Animals and Samples From April to December 2017, a total of 369 cats with access to outdoors from veterinary medical centres, animal shelters and colonies from four Portuguese continental NUTS (Nomenclature of Units for Territorial Statistics) II, were studied (Table  1 ). Peripheral blood (1-2 mL) was obtained by cephalic or jugular venipuncture from each animal and collected into EDTA and serum-separating tubes. Serum, plasma, and buffy coat were obtained from each animal by centrifugation and stored at -20 • C until used in serological analyses (serum and plasma) and DNA extraction (buffy coat). Whenever available, individual data were recorded for each cat. Of these, 350 serum and buffy coat samples had been previously used in an epidemiological study regarding exposure to P. perniciosus saliva and the presence of Leishmania infection  [15].
This work was partially supported by Bayer Animal Health, Germany and Global Health and Tropical Medicine Center (UID/Multi/04413/2013) and by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316. AP and CM have the support of the Portuguese Ministry of Education and Science (via Fundação para a Ciência e a Tecnologia, I. P. ), through a PhD grant (SFRH/BD/116516/2016) and an Investigator Starting Grant (IF/01302/2015), respectively. PV, TS and TL are supported by ERD funds, project CeRaViP (16_019/0000759) and UNCE 204072.
Funding: This work was partially supported by Bayer Animal Health, Germany and Global Health and Tropical Medicine Center (UID/Multi/04413/2013) and by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316. AP and CM have the support of the Portuguese Ministry of Education and Science (via Fundação para a Ciência e a Tecnologia, I. P. ), through a PhD grant (SFRH/BD/116516/2016) and an Investigator Starting Grant (IF/01302/2015), respectively. PV, TS and TL are supported by ERD funds, project CeRaViP (16_019/0000759) and UNCE 204072.
PATIENTS AND METHODS Data collection -Surveillance of human listeriosis in France is based on mandatory reporting of cases to Santé Publique France since 1999 and voluntary submission of Lm strains to the National Reference Center for Listeria (NRCL)  (20). The exhaustiveness of this reporting is estimated by capture-recapture at least 87%  (1). All cases declared between January 1999 and June 2018 with mention of "endovascular infection", "aneurysm" "aneurysmal infection", "cardiac device" "pace-maker", "vascular device", "endocarditis", "infected thrombus" and "endovascular infection" were included. In addition, all patients with similar mentions whose strains had been sent to the NRCL between 1993 and 1999, before the mandatory reporting era, were also included. No case of myocarditis was identified.
Characterization of Lm isolates -Characterization of all Lm isolates was performed in the context of epidemiological surveillance of listeriosis. For species identification of isolates collected before January 2017, we used the API-Listeria identification microgallery (bioMérieux, Marcy l'Etoile, France). For isolates collected after January 2017, MALDI-TOF mass spectrometry was performed using a microFlex LT/SH MALDI-TOF MS instrument (Bruker Daltonics) as previously described  (25). The MALDI BioTyper (MBT) compass explorer software v4. 1. 60 (Bruker Daltonics, Bremen, Germany) was used for spectra analyses and comparison with the MALDI BioTyper Reference library (database [DB-5989] MS; Bruker Daltonics) for automatic species identification. API-Listeria or MALDI-TOF mass spectrometry were combined to hemolysis test on horse blood agar and incubated 24 hours at 37°C  (26).
Genome sequencing was performed as previously described  (27). Multilocus sequence typing (MLST) clonal complexes (CCs)  (28) , PCR serogrouping  (29)  and core genome MLST (cgMLST) profiles  (30)  were deduced from genome assemblies using the BIGSdb-Lm platform (http://bigsdb. pasteur. fr/listeria). Histological analyses -Four µm thick sections of paraffin-embedded tissue samples were stained with hematoxylin-eosin (HE). Lm was labeled by immuno-histochemistry (IHC) using a polyclonal rabbit antiserum that detects Lm serotype 1a/b (Listeria O I/II antiserum Seiken kit; Denka Seiken Co. , Tokyo, Japan) and a goat anti-rabbit antibody coupled to peroxidase (EnVision+, Dako), followed by hematoxylin counterstaining. Images were captured with the cellSense software on an Olympus IX81 microscope equipped with an x100 objective.
Detailed echography data were reported in 27 cases. Twenty-six patients (26/27, 96%) had major criteria for endocarditis, with typical oscillating valvular vegetation (n=17) and/or cardiac abscess (n=7) or prosthetic valve dehiscence/ new paravalvular regurgitation without vegetation or abscess (n=3). One remaining patient had a thrombus on his mono-ventricular assistance device, that was retained as a minor criterion for endocarditis in the context of concomitant fever, inflammatory syndrome and Lm documentation on this thrombus (Table  3 ). Laboratory features -Lymphopenia (lymphocyte count < 1000 cells /mm 3 ) was reported in 15/36 (42%) patients (10/21 (48%) and 5/15 (33%) patients with vascular infections and endocarditis, respectively). C-reactive protein level < 20 mg/L was only reported in one patient with vascular infection.
The relevant laboratory features are summarized in Tables  2  and 3. Microbiological data -All infections were culture-proven, and the 71 strains were analyzed in the NRCL. Microbiological features are detailed in Tables  2  and 3. One patient with aneurysmal infection was infected with an avirulent Listeria species, Listeria innocua, evidenced in a per-operative sample. All others had L. monocytogenes collected. Blood cultures: Blood cultures were performed in all patients with endocarditis and in 27/42 (64%) patients with vascular infections. They were positive in 26/29 (90%) patients with endocarditis, and in 10/27 patients (37%) with vascular infections, including 5 who were reportedly afebrile (5/10, 50%).
Acknowledgements We thank  Dr. Isabelle Serre  ( Gui Chauliac University Hospital, Montpellier, France ),  Dr. Valérie Hervieu  ( Edouard Herriot University Hospital, Lyon, France ),  Dr. Beatrice Luciani-Laillou  (Périgueux, France) and  Dr. Luc Marcellin  ( Hautepierre University Hospital, Strasbourg, France ),  David Hardy  and  Magali Tichit  ( Experimental Neuropathology Unit, Institut Pasteur, Paris ) for their contribution to histopathology studies, as well as  Giulia Nigro  ( Molecular Microbial Pathologenesis Unit, Institut.
Phase 1 will be a case study in the two hospitals involved in the study, exploring knowledge of and support for PA practice among medical staff. Through interviews and documental analyses, the PA support dynamic will be evaluated with regard to PA prescription. Phase 2 will be a one-year observational study among 693 cancer patients. Quantitative medical, social, dispositional and psychological data, PA practices and preferences, will be collected at diagnosis, and six months and one year thereafter. Phase 3 will be a retrospective study, evaluating societal and policy factors, as well as unexpected factors playing a role in PA levels and preferences among cancer patients. For this phase thirty patients will be identified six months after inclusion on the basis of their PA profiles. Quantitative data will provide the main dataset, whilst qualitative data will complete the picture, enabling determinants of PA practice and their interactions to be captured throughout the cancer trajectory.
Ethics approval Verbal informed consent will be obtained from each participant and they will be allowed to withdraw at any time without any consequences. Data will be made anonymous and only the first letter of the first name and surname and a number attributed to each patient will be recorded. This research complies with the Helsinki declaration and is registered with the French National Commission for individual privacy (CNIL) and to the French committee for individual protection (CPP). This research is registered on clinicaltrials. gov (NCT03919149).
Data analysis The interviews will be fully transcribed and the content will be analyzed using both deductive methods (based on the Guide to good prescribing  [33] ) and inductive methods, where the interview content will be coded in the different dimensions of the model. Data will be interpreted by crossing responses obtained from the medical staff, to see which dimension of the Guide to good prescribing  [33]  can be applied, and to determine cancer patient trajectories. In addition, between and during the interviews, the means deployed to prescribe or support PA will be collected and analyzed, to enrich the data for each case.
Scales The questionnaire will include four main sections and different scales: medical and socio-economic variables, personality traits, situational variables and physical activity. The scales will be chosen on the basis of their validation in French and their suitability to PA and cancer patients, when available. Medical data will be completed by the clinical research assistant, and will include: patient care plan, actual patient trajectory (treatment completion, frequency, type), symptoms and complementary treatment (fatigue, pain, nutrition). Sociological variables will include age, gender, education, socio-professional category, professional activity, marital and socio-economic status, and place of residence. An 11-item scale to evaluate precariousness and health inequality (EPICES scores,  [37] ) will explore all the dimensions of precariousness.
Life habits (tobacco, alcohol, substance use) and PA practice before diagnosis will help to identify inter-determinant relationships. Medical data (co-morbidities, fatigue, sleep, pain) will also be collected from patients' perspective. Personality traits will be approached via two validated scales: Trait Hope  [38]  and Trait Optimism  [39]. Trait Hope will be assessed using the Dispositional Hope Scale  [40] , validated in French  [38]. The Trait Hope Scale contains four "agency" items, four "pathway" items, and four "filler" items. Respondents will be asked to rate the items on an 8-point Likert scale ranging from 1 "definitely false" to 8 "definitely true". The Life Orientation Test-Revised (LOT-R,  [39] ), comprises six items and four fillers, and will be rated on a 5-point Likert scale, ranging from 1 "strongly disagree" to 5 "strongly agree".
Data analysis The analyses will be performed using SPSS and SAS software. Basic descriptive statistics, including means, standard deviations and frequencies will be calculated. A comparison of PA levels will be made across groups of patients depending on their hospital site and cancer localization. An identification of PA profiles and trajectories during the study will be conducted using a latent class growth analysis  [47]. Relationships between the individual and interpersonal variables of the socio-ecological model will be tested using multilevel structural equation modeling. Profiles of PA practice among cancer patients will also be approached through the qualitative data collection, to identify further societal and policy factors, using Nvivo software.
ecdc. europa. eu/en/disease-vectors/surveillance-anddisease-data/mosquito-maps). The vectorial status of mosquitoes was inferred from experimental data using infections in laboratory and/or viral detections in field-collected populations. This review follows the PRISMA Journal Publishing protocol workflow  [18] ; the PubMed and Web of Science databases were screened from 11 January to 15 August 2019, with keywords presented on Supplementary File 1. Full-text articles in English language containing information on mosquito vector competence were selected. Articles in other languages containing critical information were included in the data set as "identified by other sources". The PRISMA flow chart is described in Figure  1.
In addition, autologous bone therapy may fail, due to preterm transplant resorption  [9, 10]. MSCs have been shown to be present in almost every tissue  [11]. Due to their limited number in tissues, MSCs have to be isolated from the original tissue and expanded ex vivo in clean rooms (class A in B)  [12À14]. Different protocols for Good Manufacturing Practice (GMP)-compliant isolation and expansion of MSCs have been described previously [15À21], but there is a lack of information on the suitability of pre-clinical protocols for experimental settings and animal models and their translation for GMP-compliant manufacturing of MSCs for clinical trials. We present the validation and translation of a standardized pre-clinical protocol  [12]  for isolation and expansion of MSCs for a clinical trial for reconstitution of alveolar bone (Jaw bone reconstitution using a combination of autologous mesenchymal stem cells and biomaterial prior to dental implant placement; MAXILLO-1 [EudraCT number 2012-003139-30; ClinicalTrials.
gov identifier NCT02751125]) as an example for translation of manufacturing protocols for clinical trials in other indications. Expanded MSCs for clinical applications are classified as an advanced therapy medicinal product (ATMP) according to the European Medicines Agency (EMA) regulation number 1394/2007 of the European Commission (EC)  [22]. In this study, we describe the translation of a previously established protocol for GMP-compliant largescale expansion of bone marrow (BM)-derived MSCs  [12]  to produce clinical doses of 50À100 million MSCs for jawbone reconstruction prior to dental implant surgery for 11 patients participating in the clinical trial MAXILLO-1. The MSCs expanded according to the GMP-compliant protocol used in this study have previously been tested for their osteogenic in vivo bone formation potential in pre-clinical models  [23, 24].
Ethical approval and participating manufacturing and clinical centers BM (validation runs) was collected from volunteer healthy donors after written informed consent was obtained according to the Declaration of Helsinki and approval by the Ethics Committee of Ulm University (ethical approval numbers 21/10 and 24/11). The clinical trial MAXILLO-1 (Jaw bone reconstruction using a combination of autologous MSCs and biomaterial prior to dental implant placement) was approved by the Norwegian ethical committee (2013/1284/ REKvest) and by the Norwegian Medicines Agency (13/12062-15). The clinical trial followed the European guidelines for advanced therapeutic medicinal products. The EudraCT number of the trial was 2012-003139-50 and the trial was incorporated in the database ClinicalTrials. gov with the identifier NCT 02751125.
Statistical analysis Statistical analysis was performed using GraphPad Prism 7. 01 Software for Windows. D'Agostino & Pearson normality test was performed for each dataset to test for normal distribution of data. In case of normal distribution, data were compared using the unpaired t test with Welch's correction; for datasets not passing the D'Agostino & Pearson normality test, data were compared using the Mann-Whitney U test. Kruskal-Wallis test was used for multiple-parameter analyses. Differences were considered as significant for P < 0. 01 because of multiple testing of the dataset. The correlation between multiple parameters was assessed, computing Spearman correlation (r values) for every pair of the following datasets: time between end of aspiration and end of seeding (h), age (y), aspiration volume (mL), aspiration volume without heparin (mL), white blood cell count ([WBC]/mL), mononuclear cell count ([MNC]/mL), % MNC of WBC, % CD34+ in BM aspirate, harvest density of MSCP0 (cells/cm 2 ), harvest density of MSCP1 (cells/cm 2 ), doubling time of MSCP0 (h), doubling time of MSCP1 (h), population doublings in P0, population doublings in P1, cumulative population doublings, CFU-F/10 6 BM-WBC, CFU-F/ 10 6 MSCP0, CFU-F/10 6 MSCP1, MSCP0 harvested/ mL BM aspirate seeded and MSCP1 harvested/mL BM aspirate seeded.
Donor characteristics Overall, 13 aspirations were performed in the context of the clinical trial MAXILLO-1 and 21 aspirations of BM were performed for validation. Production of two of the 13 aspirates for clinical trial MAXILLO-1 was stopped at passage 0 for patients 1-05 and 1-10 because the overall harvest of 0. 9 £ 10 6 and 1. 2 £ 10 6 cells in passage 0 was not sufficient to start passage 1. In accordance with this, no CFU-F/10 6 BM-WBCs were detected (data not shown). One BM from the validation was split (identification [ID] 7585) and two BM aspirates from patients within MAXILLO-1 had to be discarded (ID 1-05 and 1-10) due to lack of CFU-F in the aspirate and growth of the culture during the passage 0 growth phase (data not shown). Information on shipping and donor characteristics are presented in Supplementary Table  5  and Supplementary Figure  1  and summarized in Table  1.
Acknowledgments We appreciate the excellent assistance of  Gisela Baur ,  Thomas Becker ,  Sarah Chester ,  Dorothee Erz ,  Silva Hopfensitz  and  Christina Sp€  ath from the  Institute for Transfusion Medicine, University Hospital Ulm  and of the study coordinator  Marianne Emblem Lehmann  from  Haukeland University Hospital, University of Bergen. We would like to thank  Dr. Daniel F€  urst from  Institute for Transfusion Medicine, University Hospital Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service  for statistical advice. This work was supported by the  European Union 's  Seventh Framework Programme  for research, technological development and demonstration (grant number  HEALTH-2009-1. 4. 2-241879 (REBORNE) ). The materials presented and views expressed here are the responsibility of the author(s) only.
found no significant effect of splenectomy on overall survival or NRM in a large cohort of splenectomized patients undergoing allogeneic SCT with either reduced intensity conditioning (RIC) or MAC (n=180) registered in the EBMT registry database and nor did the retrospective Center for International Blood and Marrow Transplant Research (CIBMTR) study. 34, 35 Moreover, given the potential splenic effects of JAK inhibitor therapy, alternative methods of reducing bulky splenomegaly are possible. Lastly, it is unknown what effect pre-transplant spleen removal will have on immune reconstitution. In general, it is the view of the authors that pre-transplant splenectomy cannot be routinely recommended although it is clear that individual patient-stratified assessment should occur. Lowdose splenic irradiation prior to transplantation has been explored in small cohorts of patients, but overall there is insufficient evidence on this strategy.
PATIENTS AND METHODS Dutch, English, French, German, and Scottish transplant centers were asked to participate in this retrospective study; 30 of them agreed. We collected data from 280 SOT recipients with chronic autochthonous HEV infection who were treated with ribavirin monotherapy between September 2009 and March 2018. Chronic hepatitis was defined as a persistent replication of HEV for at least 3 months. Patients who had persistent increase in liver enzyme levels lasting for >3 months before first screening for HEV and diagnosis and who were treated before the third month after diagnosis were considered to have chronic hepatitis. Patients who were treated during the acute HEV phase and those without a complete follow-up (ie, <6 months' follow-up after ribavirin cessation) were excluded (n = 25).