dataesr/scientific-paragraphs-categorization huggingface dataset:
e. spoligotyping and 24-loci MIRU-VNTR typing. The study included 130 MDR-TB isolates, recovered from as many patients from Pakistan, between January 2013 and June 2015. Conventional drug susceptibility testing was performed using the standard 1% proportion method on the Löwenstein-Jensen medium, as described elsewhere. Spoligotyping was performed with a commer-cially available kit (Mapmygenome India Ltd. , Madhapur, India) according to the manufacturer's protocol. MIRU-VNTR analysis was carried out at 24 loci, as described earlier. Phylogenetic clades of M. tuberculosis were assigned according to signatures provided in the SITVIT database (http://www. pasteur-guadeloupe. fr:8081/SITVIT_ ONLINE). Spoligotypes were obtained for 127 (97. 8%) isolates. Based on a SIT number in the SITVIT database, all isolates presented 53 different profiles split into 14 clusters (n = 88, 69.
Conclusions To accelerate development of improved treatments for agitation, novel measures are needed to better capture behaviors that are of most concern to patients and caregivers. Operationalizing the IPA criteria is a needed first step, for diagnosis and to establish entry criteria for clinical studies. Some Task Force members advocated developing a single measure that reflects agitation as a unitary phenomenon. Since the development of new scales from whole cloth will result in additional regulatory challenges the consensus was that the best approach moving forward is to use existing datasets to construct an evidencebased single novel measure of agitation by selecting item subsets of existing scales (e. g. , NPI-C or CMAI) that best reflect the IPA criteria and the situations in which agitation occurs.
In other words, using our approach we may study predominantly the transformed cells from virtually all patients. In this study we analyzed 55 consecutives PDX obtained as described above. Other study, use PDX as PDAC tumor avatars as well as cell lines derived from PDX. Authors clearly shows that patients derived models are representing the heterogeneity of PDAC and exhibits the same mutational landscape and transcriptomic profile than the original tumor. Low passages PDX models are clustered together with the primary tumor in unsupervised analysis showing a good picture of the primary tumor phenotype  21. Unsupervised transcriptome analysis reveals two clusters of PDAC. RNA from 55 PDX was hybridized on Affymetrix arrays in duplicate. An unsupervised hierarchical clustering of the data obtained by an Euclidian distance, after the replicative averaging, of the 110 transcriptome (55 patients in duplicate, the correlation matrix of samples is provided in Supplementary Table  1 ) reveals 2 main groups of PDAC, one containing 12 patients (cluster 1) and the other one contains the 43 remaining (cluster 2) (Fig.
Supervised transcriptome analysis reveals E2F-highly dependent and E2F-lowly dependent clusters of PDAC. Then, because the E2F activated pathway appears as a classifier of PDAC, we tried to select all the patients with a significant high E2F target expression level. Therefore, we selected a set of 196 transcripts (see Supplementary Table  4 ) which expression is dependent of E2F transcriptional activity from the Molecular signatures database (MSigDB) 3. 0. 22 and performed a supervised clustering on the same set of PDX. Using this clustering criteria we observed that 4 PDX (CRCM12, CRCM91, CRCM76 and CRCM110) switched from cluster 1 to E2F low and 7 PDX switched from cluster 2 to E2F high (CRCM22, CRCM79, CRCM82, CRCM84, CRCM87, CRCM88 and CRCM94) indicating a more precise E2F-dependency classification as showed in Fig.
In Fig. 2c  are represented all the 55 patients and the strategy seems to be efficient since all the E2F high patients (in red) are well differentiated from the E2F low (in blue). Only 5 patients resulted in false positive (in gray). Finally, we validated the 24-genes E2F signature in external cohort of PDAC from the TCGA consortium. From the original signature composed by 24 markers, data weren't available for three markers (LOC100505633, DLEU7-AS1, and RHBDL2). The 24-genes signature is able to discriminate two clusters of patients named respectively TCGA E2F high and TCGA E2F low. Surprisingly, the DFS and OS of the 17 TCGA E2F high patients are reduced compared to the TCGA E2F low subgroup (Supplementary Figure  3 ).
Material and Methods PDAC samples and cell culture. Patients were included under the Paoli Calmettes Institute clinical trial NCT01692873 (https://clinicaltrials. gov/show/NCT01692873). Three expert clinical centers collaborated on this project after receiving ethics review board approval. Consent's forms of informed patients were collected and registered in a central database. The tumor tissues used for xenograft development was deemed excess to that required for the patient's diagnosis. All the samples were anonymized. Two types of samples were obtained, namely Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) biopsies from patients with unresecable tumors, and tumor tissues from patients undergoing surgery. Fifty five xenografts were included. PDAC samples were mixed with 100 µl of Matrigel (BD Biosciences) and implanted with a trocar (10 Gauge, Innovative Research of America, Sarasota, FL) in the subcutaneous right upper flank of an anesthetized and disinfected mouse.
Gene expression microarrays. Total RNA was purified from xenografts using TRIzol ® Reagent (Gibco, Life Technologies) according to the manufacturer. RNA Integrity Number (RIN) was calculated using the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA). RNA samples that reached a RIN over 8 were used for microarray hybridization (GeneChip; Affymetrix Inc. , Santa Clara, CA). The Genechip ® Human Gene 2. 0 ST Arrays were washed and stained using the Affymetrix GeneChip fluidic station 450 (protocol EukGE-WS2v5_450) and were scanned using a GeneChip scanner 3000G7 (Affymetrix Inc. , Santa Clara, CA). GeneChip operating software version 1. 4 (Affymetrix Inc. , Santa Clara, CA) was used to obtain chip images and for quality control. Microarray analysis was performed in duplicate for each PDX samples by the CHU de Québec Research Center Gene Expression Platform (Quebec City, Quebec, Canada).
For each sample, the mean of duplicates is used for further computational analysis. Hierarchical clustering of complete linkage with the Euclidian metric (for samples) and Pearson correlation (for genes) was performed by the use of BRB-array tools version 4. 6. 0 (http://linus. nci. nih. gov/BRB-ArrayTools. html). The robustness (R) indices and the discrepancy (D) indices (BRB-array tools) were calculated to give an indication concerning the reproducibility of the clusters. Effect of ly101-4B on the transcriptome of MiaPaCa2 cells was analyzed after the treatment with 25 µM for 24 h on the Affymetrix platform as described above. The Gene Expression Omnibus (GEO) (http://www. ncbi. nlm. nih. gov/geo) accession numbers corresponding to our dataset are GSE55513 (17 samples) and GSE89792 (38 samples).
43. Two indices of the clustering robustness are provided. The R index measures the reproducibility of the cluster. An index R of 1 means perfect reproducibility. The D index measures the number of discrepancies (additions or omissions) comparing an original cluster to a cluster that best matches the perturbed data. An index R of 0 no discrepancies despite data perturbation. The heatmap illustrations were made on GENE-E software (version 3. 0. 204; Broad Institute, Cambridge, MA, USA). Differentially expressed genes between the AHC clusters were identified using permutation t-test with welch correction. The pvalues were adjusted for false discovery rate using Benjamini & Hochberg method  44. The threshold of significance was set at adjusted-p-value < 0. 05. Gene set enrichment analysis (GSEA) was performed using the Broad Institute platform and statistical significance (false discovery rate) was seated at 0.
Statistical analysis. The overall survival and relapse-free survival were analyzed using the Kaplan-Meier log-rank test to assess differences in survival. A t-test was used to assess the statistical significance of mean differences between two groups. The IC50 values were calculated from a log ([drug]) versus normalized response curve with robust fit using GraphPad Prism software v5. 0 (GraphPad Software). Data for cell viability assays were analyzed using one-way repeated analysis of variance (ANOVA) with Dunnett post-hoc test for multiple comparisons. A p-value < 0. 05 is considered significative.
Fluorescence microscopy image acquisition and analysis Cells were grown at 37 °C/5%CO 2 in CY to OD 595 nm 0. 3, transferred to microscope slides, and observed at 37 °C on an Olympus BX61 microscope equipped with a UPFLN 100O-2PH/1. 3 objective and a QImaging Retiga-SRV 1394 cooled charge-coupled-device camera or an Olympus IX81 microscope equipped with a UPFLN 100O-2PH/1. 3 objective and a Hamamtsu Orca Flash4 camera. Image acquisition was performed using the software packages Volocity. Images were analyzed using the open-source softwares MicrobeTracker  (Sliusarenko et al. , 2011)  and Oufti  (Paintdakhi et al. , 2016)  and processed with Adobe Photoshop CS5 and Image J. Demographs integrate the signal values in each cell. The cells were sorted by their length value and the fluorescence values were plotted as a heat map.
45), a Semrock filter set for GFP (Ex: 482BP35; DM: 506; Em: 536BP40) a LED light source (Spectra X Light Engine, Lumencor), a sCMOS camera (Neo sCMOS, Andor) and a chamber thermostated at 37 °C. Fluorescence images were capturated and processed using Nis-Elements AR software (Nikon). GFP fluorescence images were false colored green and overlaid on phase contrast images.
In the meantime, a population of sfGFPop-LytA remains associated to the former parental division site, which corresponds to the new poles of the daughter cells (v). We also investigated in real-time the localization of sfGFPop-LytA during cell division in a microfluidic system. sfGFPop-LytA was pulseinjected on cells before extensive wash with CY medium. The Fig. 6. Localization of LytA and cell wall cleavage sites. A. The CBD is sufficient to trigger localization of LytA. Wild-type cells in exponential growth phase were incubated with sfGFPop-LytA or sfGFPop-LytA CBD recombinant proteins (10 µg/mL). Merge image of fluorescence and phase contrast views are showed. Scale bars: 2 µm. Demograph representation of the signal profile of sfGFPop-LytA and sfGFPop-LytA CBD in cells sorted by increasing cell length (MicrobeTracker, MATLAB).
Acknowledgements This work used the platforms of the Grenoble Instruct-ERIC centre (ISBG;  UMS 3518 CNRS-CEA-UGA-EMBL ) with support from  FRISBI  ( ANR-10-INSB-05-02 ) and GRAL ( ANRS-10-LABX-49-01 ) within the  Grenoble Partnership for Structural Biology  (PSB). The electron microscopy facility is supported by the  Rhône-Alpes Region , the  Fondation pour la Recherche Médicale (FRM) , the fonds  FEDER , and the  GIS-Infrastructures en Biologie Santé et Agronomie (IBISA). J. B. received a PhD fellowship from the  French Ministry of Education and Research. We thank  Kousik Sundararajan  for assistance with  TEM (Hilde Kolstad, Norway) Yves Brun ,  Erkin Kuru  and  Michael van Nieuwenzhe (Bloomington University)  for providing HADA and  Guy Schoehn  for support. We are grateful to  André Zapun  for helpful discussions.
A phase 3 trial for the treatment of refractory or resistant infection in transplant patients is ongoing. Letermovir, a novel non-nucleoside CMV inhibitor targeting the viral terminase complex, was approved by the FDA in 2017 for the prevention of CMV infection in bone marrow transplantation. In this population, a phase 3 randomized trial is showing a superior efficacy of letermovir compared with placebo in preventing CMV disease  52  with myelotoxicity and nephrotoxicity rates similar to those of placebo. Successful outcome was reported with compassionate use of letermovir in a lung transplant patient with CMV-resistant disease  53. Letermovir was also shown to be effective in treating CMV viremia in kidney transplant recipients  54  , and a clinical trial comparing letermovir with valganciclovir for the prevention of CMV disease in donor-positive/recipient-negative kidney transplantation is starting (ClinicalTrials.
gov identifier: NCT03443869). However, caution should be exercised in treating CMV infection with letermovir alone, as in vitro studies have shown rapid emergence of resistance on treatment  55. The lipid-conjugated analogue of cidofovir, brincidofovir, has high oral availability and less nephrotoxicity than cidofovir. Efficacy has been low in prevention in hematopoietic stem cell transplant patients, and few data are available in SOT recipients  56. Moreover, Faure et al. reported two cases of acute kidney injury in SOT patients who received brincidofovir  57.
Cytomegalovirus In vitro tests have been developed to detect the release of interferon-gamma (IFN-γ) induced by stimulation of lymphocytes by CMV antigens. The most used test is QuantiFERON-CMV assay (Qiagen Ltd. ), a commercially available enzyme-linked immunosorbent based assay  59. Several studies showed that positivity of QuantiFERON-CMV at the end of prophylactic valganciclovir correlates with lower incidence of CMV disease  60, 61  and that patients with low viremia were more likely to have spontaneous clearance if they had positive QuantiFERON-CMV  62. However, data showing the use of this test in daily practice were missing. Recently, Kumar et al. reported the results of an interventional study using QuantiFERON-CMV in real-life practice  63. Patients were enrolled at completion of treatment for the first episode of CMV reactivation, and a QuantiF-ERON-CMV test was done with results available within 3 days.
Quantitative digital image analysis of immunohistochemical staining and statistical analyses Quantitative comparison of immunohistochemical staining was measured by ImageJ, a digital image analysis public domain software (U. S. National Institutes of Health, Bethesda, MD; available at: https://imagej. nih. gov/ij/) for all antibody tested in the study. Five microscopic fields were selected from control and DSS groups, photographed at the same magnification and then subjected to IHC profiler software analysis. The immunopositivity was expressed as a percentage of the total softwareclassified areas and the data obtained were plotted as histograms. Results were expressed as means ±SD; a P-value <0. 05 was considered statistically significant.
Weeds were controlled with bispiribac sodium. Three experimental conditions were included in the assay; no SA application (SA0, control condition), application of 1 mM SA (SA1), and application of 15 mM SA (SA15). These treatments were sprayed 10 and 17 days after anthesis. The SA solutions were prepared in distilled water with 50 ppm Tween-20 surfactant. The plots were sprayed in late afternoon hours, under wind conditions of less than 10 km•h -1. Regarding environmental conditions, the arable area evaluated was exposed to two diverse growing conditions: one was covered with plastic of 100 μm thickness between the second SA application and harvest (crop EP), and the other was grown in the open (crop E). Temperature values were recorded by an XR440 Pocket TM data logger (Pace Scientific Inc.
Funding This work was partially funded by the  Fundacioń Seńeca de la Regioń de Murcia Grupo de Excelencia   19900/GERM/15. This work is included in the framework of the collaboration between the  Spanish Research Council (CEBAS-CSIC)  and  CNRS-University of Montpellier by Projets Internationaux de Cooperation Scientifique  ( PICS-2015-261141 ). M. P. was sponsored by a predoctoral fellowship of the  Asociacioń Universitaria Iberoamericana de Postgrado  ( RR 631-2016 ) of the  University of Murcia (Spain). R. D. -P. was sponsored by a postdoctoral contract ( Juan de la Cierva de Incorporacioń   ICJI-2015-25373 ) from the  Ministry of Economy, Industry and Competitiveness of Spain. We thank the English expert reviewer ( Dr. David James Walker ) for revision of the English style and grammar.
Study Design This study was an open-label, single-ascending-dose, exploratory study of 12 patients approved by a certified medical ethics review board (clinicaltrials. gov ID: NCT02973672). The study primarily aimed to assess SGM-101 with respect to tolerability and performance in the intraoperative detection of PDAC lesions. Due to the exploratory nature of the study, sample size was not based on a formal calculation of statistical power. A doseescalating scheme with intravenous doses of 5, 7. 5 and 10 mg administered 48 or 96 h before surgery was used based on our preclinical data. 18 We included patients with elevated plasma CEA levels ([ 3 ng/mL) who had a clinical diagnosis of PDAC and were scheduled for surgical exploration. The exclusion criteria ruled out pregnancy, history of allergic reactions, impaired renal function, plasma CEA level higher than 300 ng/mL and a diagnosis of another malignancy within the last 5 years.
Subsequently, the fluorescence imaging system was used to identify NIR-fluorescent lesions. All lesions identified by visual/tactile methods and/or NIR fluorescence were resected if resection was surgically feasible and clinically relevant. Each resected lesion was marked on a case report form as fluorescent or non-fluorescent and as clinically suspected of malignancy or not. After resection, fluorescence imaging of the resected specimen (before and after slicing) was performed in the pathology department. The slice containing the peak fluorescence signal was imaged using the Pearl imager and corresponding software (LI-COR, Lincoln, NE, USA). The fluorescence signal in tumor and background tissue (tumorto-background ratio [TBR]) was quantified using ImageJ (version 1. 49b; NIH, Bethesda, MD, USA; http://imagej.
Safety Data One patient (ID no. 208) experienced mild, self-limiting abdominal discomfort and diarrhea on the day of SGM-101 administration (dose, 7. 5 mg), although these symptoms likely were not related to SGM-101. Causality could not be excluded. In the remaining patients, adverse events related to SGM-101 were not seen. After the surgical procedure, four severe adverse events were noted, all related to the surgical procedure or to disease progression.
CT or MRI was used to distinguish ischaemic from haemorrhagic strokes. Definite ST was classified according to the Academic Research Consortium criteria. 7 Bleeding episodes were classified according to the Bleeding Academic Research Consortium (BARC) classification. 8 ll data were collected prospectively using standardised questionnaire and were entered into a central database. Follow-up was planned for 6 months after inclusion or until the time of death, whichever came first. All events were adjudicated by a local research committee that was unaware of treatment allocations. All thrombotic and bleeding events requiring medical attention were verified by research nurses who were blinded to the patient's study group by use of medical records obtained from referring family doctors and hospitals.
statistical analysis All calculations were performed using SPSS software (version 20. 00) and GraphPad prism (version 7. 0). Continuous variables were reported as means and SD or as medians and range (according to their distribution), and categorical variables were reported as count and percentages. Standard two-sided tests were used to compare continuous characteristics (Student's t-tests or Mann-Whitney U-tests) or categorical characteristics (χ 2 or Fisher's exact tests) among patient groups. As a Interventional cardiology measure of strength of the treatment effect, we calculated HR and 95% CI for 'Cohort B' versus 'Cohort H' by means of Cox's proportional hazards regression analysis. 1 ). The rate of definite ST at 30 days was low and not different between the two groups (three (0. 5%) patients in Cohort B vs two (0.
Sequence identification and domain characterization All amplifications to generate the full-length coding sequences of TLR3, 7, 8 and 9, RIG-I, MDA5, LGP2 as well as IFNa1 and partial bactin sequence were performed on cDNA obtained from liverextracted RNA, while the complete sequence of IFNb was obtained using RNA extracted from the poly (I:C) transfected FLuDero cell line. Internal coding regions were amplified by PCR using the AmpliTaq Gold DNA polymerase kit (Thermo Fischer Scientific). Different combinations of consensus and specific degenerate primers were designed using Primer3 (v. 0. 4. 0) based on alignments of orthologous mammal sequences (bat, equine, swine, feline, bovine and human) available in the GenBank database (Supplementary Table  1 ). The 5 0 -and 3 0 -terminal sequences were obtained by rapid amplification of cDNA ends (RACE) using the FirstChoice ® RLM-RACE Kit (Ambion, Inc.
). PCR and RACE products were cloned using the pCR™4-TOPO ® TA CLONING ® KIT (Invitrogen). The sequences obtained were confirmed by similarity analysis using the NCBI BLAST search (http://www. ncbi. nlm. nih. gov/BLAST). Structural domains of RLRs were identified using SMART software (http://smart. embl-heidelberg. de/) (Letunic et al. , 2015).
RLRs phylogenetic analysis The complete coding sequences for RIG-I, MDA-5, LGP2, IFNa1 and IFNb of representative Laurasiatherian and Euarchontoglires and of a marsupial (Monodelphis domestica) were downloaded from the NCBI Database. Three (IFNa1), nine (MDA-5, LGP2) and ten (RIG-I, IFNb) bat sequences were available (Supplementary Table  2 ). The sequences of D. rotundus obtained in this study were further added to each data set. After alignment and editing, the MEGA version 6. 0 software  (Tamura et al. , 2013)  was used to determine the best-fit amino acid evolutionary substitution model (Jones-Taylor-Thornton þ G þ F), and phylogenetic analyses were performed under maximum-likelihood criteria with 500 bootstrap replicates. All trees were rooted with the marsupial Monodelphis domestica or rodent Mus musculus sequences.
IFNb showed lower similarity with its mammalian homologs, ranging from 50 to 60% at the amino acid level. Through phylogenetic analyses, we then showed that all the D. rotundus sequences generated belonged to a single clade of chiropters (Supplementary Figs. S3  and S4 ). The phylogenetic trees generated were in agreement with the different mammalian orders. Nevertheless, for the RLRs, the relationships between these orders were weakly supported by bootstrap analysis (Supplementary Fig. S3 ). These sequences were submitted to GenBank under accession numbers MF121906eMF121914.
Acknowledgments This study was conducted within the  CAROLIA and BATIMMUNE  programs. CAROLIA was supported by  European funds (ERDF/ FEDER)  and assistance from the  R egion Guyane  and the  Direction R egionale pour la Recherche et la Technologie. BATIMMUNE was funded by the  Institut Pasteur  through a  Transversal Research Program  ( PTR499 ). This study also received a  European Commission "REGPOT-CT-2011-285837-STRonGer" grant  within the  FP7 and an "Investissementd'Avenir " grant managed by the  Agence Nationale de la Recherche  ( CEBA, Ref. ANR-10-LABEX-25-01 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Appendix A. Supplementary data.