dataesr/scientific-paragraphs-categorization huggingface dataset:
4 in the USA extracted from a national administrative database percentage of treated 2/10 (20. 0) Providers (1 study 90 ): 90 Data on antibiotic use for patients with acute otitis externa patients MMR 2. 3 among providers in different clinical specialties (otolaryn- gologists, emergency departments physicians, paediatri- cians) in the USA percentage of non- 1/10 (10. 0) Clinics (1 study 91 ): 91 Data on inappropriate use of systemic antibiotics for chil- compliant MMR 2 dren with otitis media with effusion among 19 clinics in prescriptions the USA number of antibiotics 1/10 (10. 0) Geographical areas (1 study 92 ): 92 whose prescription is MMR 15 restricted and requires specific information confirming the diag- nosis in order for the patient to be reim- bursed by the health system.
PD2a1 and PD2b1 Integrate Input from MBON-ɑ2sc and PNs during Olfactory Stimulation Our anatomical data indicate that PD2a1 and PD2b1 integrate olfactory information from the very broadly tuned MBON-ɑ2sc and PNs encoding food odors. To directly measure the olfactory tuning of PD2a1 and PD2b1 neurons, we performed whole-cell electrophysiology, which is more sensitive than calcium imaging. We targeted GFP-labeled PD2a1 and PD2b1 neurons for in vivo recording, followed by stimulation with a large battery of different odorants (Figure  6C ; STAR Methods). As expected, we found that PD2a1 and PD2b1 neurons were broadly tuned, responding to almost all odors at the test concentrations (Figure  6C' ). Response variability was not noticeably greater than other LH neurons  (Frechter et al. , 2018). Apple cider vinegar drove the highest response, consistent with strong DM1 and/or VA2 inputs identified by EM.
We also tested two attractive monomolecular odorants, ethyl acetate and isoamyl acetate. We again found that silencing MBON-ɑ2sc attenuated odor responses in PD2a1 and PD2b1 (Figures  6H  and 6I ; see Figure  S8D  for the genotypic control). These results confirm that PD2a1 and PD2b1 integrate input from PNs and MBON-ɑ2sc. They also show that direct (PN) and indirect (MBON) pathways have different relative strengths for different odors. PD2a1 and PD2b1 Neurons Are Required for Olfactory Approach Behavior Our functional and behavioral data demonstrate that PD2a1 and PD2b1 are modulated by and necessary for aversive olfactory  memory retrieval. However, our EM reconstruction and electrophysiological characterization revealed that these neurons respond strongly to apple cider vinegar, an appetitive odor.
STAR+METHODS Detailed methods are provided in the online version of this paper and include the following: annotated synapses on PNs in the LH and Nadiya Sharifi for 4% of the MBONɑ 0 2 cable. Finally we thank Marta Zlatic, Glenn Turner and his group, and the Jefferis and Preat groups for many insightful comments on the manuscript. d KEY RESOURCES The enhancers used to create split-GAL4 hemidrivers were created based on annotations for PD2a1 and PD2b1 in a GAL4 expression pattern database  (Jenett et al. , 2012). The enhancer hemidriver lines were created using Gateway cloning. All transgenic fly lines were generated by either Bestgene or Genetic Services.
Immunohistochemistry Throughout this study we used two different immunohistochemistry (IHC) protocols. Figures  1F, 2A , 2B, and S5A used Protocol 2 while all other IHC data was processed using Protocol 1. For neurons filled during electrophysiology, see protocol for electrophysiological recording below. See Key Resources Table for antibodies used. Protocol 1 IHCs were performed as described  (Kohl et al. , 2013). Fixation was in 4% paraformaldehyde for 20 minutes. Blocking was performed with normal goat serum overnight at 4 C. Primary and secondary antibody stains were incubated at 4% for 48 hours each. After incubation with both primary and secondary antibodies, the brains were washed with 0. 5% Triton X-100 at room temperature. All specimens were mounted in Vectashield (H-1000) (Vector Laboratories, Burlingame, CA, USA).
Memory graphs were subjected to statistical analysis using 1-way ANOVA followed by Newman-Keuls pairwise comparisons between the experimental group and its controls. ANOVA is robust against slight deviations from normal distributions or the inequality of variances if the sample sizes are similar between groups which was the case in our experiments. Therefore, we did not systematically test our data for normality or verify variance homogeneity prior to statistical tests, but we rather adopted a uniform analysis strategy for all our data ANOVA results are given as the value of the Fisher distribution F(x,y) obtained from the data, where x is the number of degrees of freedom between groups and y is the total number of degrees of freedom of the distribution. Statistical tests were performed using the GraphPad Prism 5 software.
In general, both hemispheres could be recorded simultaneously. Olfactory stimuli were triggered by switching a valve to direct 30% of the total flow for 2 s through bottles containing odorants diluted in paraffin oil. Final dilution in the airflow was 1:2000. We recorded two series of responses to octanol and methylcyclohexanol, in alternating order, each separated by a 2 min interval, but only the first response to each odorant was kept for analysis. Data analysis was performed with MATLAB software. For each recording, a DF/F0 time trace trace was calculated from an ROI surrounding the PD2a1 and PD2b1 projections. The baseline F0 value was calculated from the 2 s period preceding the switch of the valve. The response integral was calculated as the integral of the time trace during 10 consecutive time points following the onset of odor response (approx.
Sparse EM Reconstruction and Neuron Identification Neurons were reconstructed by 'tracing' in a full female adult Drosophila melanogaster brain volume (x,y,z resolution 4 nm x 4nm x 40 nm) that had been acquired by serial section transmission EM  (Zheng et al. , 2018) , wherein the authors provide detailed sample preparation, EM acquisition and volume reconstruction protocols. Tracing aimed to generate a neuronal skeleton that represents the branching of neurons and the locations of their synapses, rather than a volumetric reconstruction. Manual neuronal tracing through EM serial sections was performed in CATMAID (http://www. catmaid. org) (Saalfeld et al. , 2009) , a Web-based environment for working on large image datasets that has been optimized for tracing and online analysis of neuronal skeletons  (Schneider-Mizell et al.
Ambiguities and uncertainties in each neuron were flagged as it was traced, all neurons were subsequently and iteratively proofread and edited by an expert tracer until completion at least in the region of interest (see below). Gap junctions could not reliably be identified in this dataset. MBONs-ɑ2sc and MBON-ɑ 0 2 were found by tracing downstream of extant reconstructed Kenyon cells  (Zheng et al. , 2018)  within the appropriate MB compartment  (Aso et al. , 2014a). Identity was verified with visual comparison to confocal stacks collected in  Aso et al. (2014a). Identification of PD2a1 and PD2b1 cell types began with tracing downstream of right-side MBON-ɑ2sc. 23. 95% of 1837 total outgoing connections from the right-side MBON-ɑ2sc axon in the LH were traced into 70 substantial neuronal arbors (> 300 mm of cable; data not shown).
Visual inspection identified candidates for two PD2a1 neurons, which were traced to identification. This provided the location of the PD2 primary neurite tract (see Figure  S7 ; nomenclature from  Frechter et al. , 2018). In insect brains, the majority neuronal cell bodies are positioned outside of the neuropil proper, in the cortex, and invaginate the neuropil via a primary neurite before branching. The primary neurite tract that a neuronal cell type takes is consistent between members of the type and between brains (S. F. and G. S. X. E. J. , unpublished data). No similar tract that might have also contained our neurons of interest could be found after thorough visual scanning through the EM data, nor was there any indication from NBLAST clustering of LH neurons in the FlyCirciuit database  (Chiang et al.
, 2016)  of reconstructed skeletons against MCFO data from this study and the FlyCircuit database  (Chiang et al. , 2011). Scores for our 7 putative PD2a1 and PD2b1 neurons were higher than for other candidate neurons in the PD2 tract and other MBON-ɑ2sc targets (data not shown). All 7 PD2a1 and PD2b1 neurons and the ipsilateral MBONs-ɑ2sc and MBON-ɑ 0 2 were fully traced 'to completion' ex nihilo, with synapse annotation. The contralateral MBONs-ɑ2sc was traced to identification, but completed within the LH. 'Completion' does not necessarily mean that absolutely all cable has been reconstructed and postsynapses and presynapses annotated, as a small minority of processes and connections may not have been resolved due to ambiguities in the image data. Many uniglomerular, excitatory projection neurons of the medial antennal lobe tract had been identified in the present EM volume, and traced outside the MB calyx only to identification, not completion  (Zheng et al.
ACKNOWLEDGMENTS This work was supported by  MRC LMB  graduate studentships and  Boehringer Ingelheim Fonds PhD fellowships  (to M. -J. D. and A. S. B. ) and a  Janelia  graduate research fellowship (to M. -J. D. ), ERC starting (211089) and consolidator (649111) grants and core support from the  MRC  ( MC-U105188491 ) (to G. S. X. E. J. ),  Agence Nationale de la Recherche  funding of the MemoNetworks and MemoMap projects (to P. -Y. P. and T. P. ) and the  Labex Memolife PhD fellowship  (to G. B. -G. ), the  Howard Hughes Medical Institute  (to A. W. and G. M. R. ), a  Wellcome Trust   collaborative award  ( 203261/Z/16/Z  to G. S. X. E. J. , D. B. , and G. M. R. ), and a Cambridge Neuroscience-PSL collaborative grant supported by the  Embassy of France in London  (to G. S. X. E. J. ). This work was also supported by the  HHMI Janelia Visiting Scientist Program.
Acknowledgments: We gratefully acknowledge the many co-workers and colleagues from our own team and from outside that over many years have contributed to this work. In particular, the collaborative efforts and discussion with  Karl Lohner ,  Georg Pabst ,  Martin Hof ,  Mariana Amaro ,  Marina Rautenbach ,  Robert Vácha ,  Jarbas Resende ,  Rodrigo Verly , and their teams are much appreciated. The financial contributions of the  Agence Nationale de la Recherche  (projects TRANSPEP  07-PCV-0018 ,  ProLipIn 10-BLAN-731 , membraneDNP  12-BSV5-0012 , MemPepSyn  14-CE34-0001-01 , InMembrane  15-CE11-0017-01 ,  Biosupramol 17-CE18-0033-3  and the  LabEx Chemistry of Complex Systems   10-LABX-0026_CSC ), the  IRTG Soft Matter Science (Freiburg, Strasbourg) , the  Marie-Curie Research and Training Network 33439  of the  European Commission BIOCONTROL , the  University of Strasbourg , the  CNRS , the  Région Alsace  and the  RTRA International Center of Frontier Research in Chemistry , and the  French Foundation for Medical Research (FRM)  are gratefully acknowledged.
Data were considered significantly different when p < 0 05. 2. 6. Evaluation of the NPL Tolerability. The tolerability of the NPL was studied throughout the experiment. The animals were weighed before the first nasal administration and before sacrifice. The percentage of variation was calculated, and statistical tests (one-way ANOVA with Tukey's post hoc test) were performed to determine the effect of NPL on the weight variation. The behavior of the rats was also observed with particular attention being paid to sneezing, nose bleeds, runny nose, or watery eyes during the 15 minutes following nasal administration; anxiety, pain-related disorders (aggressiveness, lack of movement, hunched posture, piloerection, ear position, eye tightening, and grooming), and death were also recorded until sacrifice.
The expected immediate adverse effects, including sneezing, nose bleeding, runny nose, and watery eyes, were observed and recorded for 15 minutes after nasal administration. The anxiety-and pain-related behaviors and endpoints including aggressiveness, lack of movement, hunched posture, piloerection, ear position, eye tightening, or grooming were observed throughout the in vivo genotoxicity assessment. Finally, the percentage of mortality was also recorded. 6 Journal of Nanomaterials damage (data This is consistent with the absence of ROS induction (Figure  3 ) and of genotoxicity without hOGG1 (Figure  4 ). At the organism level, the toxicity of a nanomaterial could be due to an accumulation in a specific cell type, tissue, organ, or compartment (e. g. , bloodstream) and could lead to the synthesis of inflammatory mediators or complement activation  [14].
Acknowledgments The authors would like to thank  Dr. Michael Howsam  for critically reading the manuscript and  Mrs. Hafssa Jaddi ,  Mr. Smaïl Talahari , and  Mr. Gonzague Dourdin  for their technical assistance. This work did not receive specific funding and was performed with the support of the  University of Lille , the  INSERM , the  CHU Lille , the  Pasteur Institute of Lille , and the  University of Artois.
Acknowledgments: We thank the many colleagues around the world who have used DRIT and especially those field and laboratory workers in Canada, Europe and the  USA  that have contributed samples during enhanced rabies surveillance. Specifically, we recognize the leadership and technical expertise of F. Cliquet,  ANSES ;  M. Niezgoda ,  L. Orciari  and  P. Yager ,  CDC ;  C. Fehlner-Gardiner ,  CFIA ;  T. Buchanan ,  Ontario Ministry of Natural Resources ;  M. Gagnier ,  Ministère des Forêts, de la Faune et des Parcs du Québec ;  J. Goltz ,  New Brunswick Department of Agriculture, Aquaculture and Fisheries ; the enhanced rabies surveillance efforts of the  USDA, APHIS, Wildlife Services  state programs, and leadership in wildlife rabies management of  R. Chipman  and  K. Nelson  from the  Wildlife Services' National Rabies Management Program.
, 2013). Of interest, SGK1 was not equally expressed in other T cells subsets, especially Th1, Th2 and in vitro TGF-β-induced Treg (iTreg). IL-23 has the capacity to induce and maintain the expression of SGK1 in Th17 cells. Using protein-protein interaction analysis from a large database, FOXO1 was identified as a transcriptional factor that had a downstream role in the expression of SGK1. SGK1 promoted phosphorylation of FOXO1, which led to reduced FOXO1 activity and increased IL23r mRNA expression and induction of RORγt, a major regulator of Th17 differentiation  (Wu et al. , 2013). The second study by Kleinewietfeld et al. reported similar results: CD4 + T cells cultured in a medium with increased salt concentration regulated SGK1 expression, and thus promoted Th17 differentiation  (Kleinewietfeld et al.
Clinical Studies Four published studies were found  (Salgado et al. , 2015; Sundström et al. , 2015; Jiang et al. , 2016; Marouen et al. , 2017). Three examined the relationship between the intake of sodium chloride and the development of RA, and one examined the relation between sale intake and disease severity. The first study used data from a large cohort of early RA from the Netherlands (EIRA study) and analyzed the impact of sodium consumption on the development of RA among smokers according to the level of sodium intake  (Jiang et al. , 2016). Sodium intake was evaluated by means of a self-report questionnaire. As expected, smoking status was found to be associated with anti-citrullinated protein antibody (ACPA)positive RA, but only in those with medium or high sodium intake [odds ratio (OR): 1.
Funding The study was funded by the  Austrian Science Fund , Project  I-2114-B27  ( ERA-Net: MELTRA-BBB ), I  3335-B27  and the  European Union ,  Marie Curie Actions -ITN ; Project  NEUROKINE 316722 ; E. S. was supported by postdoctoral fellowships for research abroad from the  Uehara Memorial Foundation  and the  Kanae Foundation for the Promotion of Medical Science.
Background: We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods: Patients received avelumab (10 mg/kg)-a human anti-PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of December 31, 2016, 51 patients were treated and followed for a median of 24. 2 months (range, 16. 1-31. 5). Most patients had cutaneous (n = 28 [54. 9%]) or ocular (n = 16 [31. 4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (n = 26 [51. 0%]). The confirmed ORR was 21. 6% (95% CI, 11. 3-35. 3; complete response, 7.
Study design and patients JAVELIN Solid Tumor is an ongoing, international, multicenter, multicohort, open-label, dose-escalation and dose-expansion, phase 1 trial of avelumab in patients with advanced solid tumors (NCT01772004). In this phase 1b, dose-expansion cohort, eligible patients had histologically or cytologically confirmed stage IIIC or IV unresectable melanoma (according to the American Joint Committee on Cancer/Union for International Cancer Control [AJCC/UICC] TNM staging system, 7th edition)  [22, 23]  and were required to have progressive disease after ≥1 prior standard therapy for metastatic disease. Other eligibility criteria included an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; age≥18 years; adequate hematologic, hepatic, and renal function; no evidence of brain metastases; and an available fresh or archival tumor specimen.
Acknowledgments The authors thank the patients and their families, investigators, coinvestigators, and study teams at each of the participating centers, at  Merck KGaA, Darmstadt, Germany , and at  EMD Serono, Billerica, MA, USA  (a business of  Merck KGaA, Darmstadt, Germany). UK has received honoraria from and is a member of advisory boards for  AstraZeneca ;  Bristol-Myers Squibb ;  Merck, Sharp & Dohme ;  Merck KGaA ; and  Pfizer. JMM reports consultancy for  Merck, Sharp & Dohme and Amgen ; reimbursement for travel and accommodations from  EMD Serono  and  Merck, Sharp & Dohme ; other relationships with  Amgen, EMD Serono , and  Merck KGaA ; honoraria from  Genentech  and  EMD Serono ; JMM's institution received research funding from  Merck KGaA ,  Sanofi ,  Novartis, Polynoma, Immunocore, Amgen , and  AstraZeneca.
The Toxoplasma gondii genome codes for two WD-40 repeat proteins of the PROPPIN family We performed homology searches in the T. gondii genomic database (www. toxodb. org) using Atg18 from Saccharomyces cerevisiae as a query, and we identified two putative homologues: TGGT1_288600 and TGGT1_220160 (Fig  1A ). Reverse BLAST analysis showed these two proteins had homology for members of the yeast PROPPIN family, namely yeast Hsv2 and Atg18. Both Toxoplasma proteins contain a putative WD-40 repeat domain (Fig  1B ) within which the conserved FRRG lipid-binding motif of PROPPINs  [8]  was identified (Fig  1B ). These two proteins had similar percentages of sequence similarity when comparing them individually with S. cerevisiae Atg18, either when considering the whole protein, or solely the WD-40 domain (Fig 1A ).
Bioinformatic analyses Sequence alignments were performed using the multiple sequence comparison by log-expectation algorithm of the Geneious software suite v5. 3. 3 (www. geneious. com). The phylogenetic tree was built with the same software suite using Jukes-Cantor genetic distance model, and unweighted pair group method with arithmetic mean for tree building. Domain searches were performed in the Pfam database (http://pfam. xfam. org/).
Virulence assays in mice Survival experiments were performed on groups of 6 mice per parasite cell line. Six to eight weeks old female C57BL/6 mice, purchased from Laboratory Animal Center of Wenzhou Medical University, were infected by intraperitoneal (i. p. ) injection of 1 000 tachyzoites freshly harvested from cell culture. ATc (Cayman CAS:13803-65-1) was added to the drinking water at a final concentration of 0. 2 mg/ml and the solution changed every 36 hrs. The water bottle containing ATc was wrapped in aluminum foil to prevent precipitation of ATc due to light. Mice survival was checked twice daily until their death, endpoint of all experiments. On day 10 postinfection, sera from surviving mice was monitored for immune response by immunoblotting against tachyzoites lysates. Data were represented as Kaplan and Meier plots using GraphPad Prism 6.
Acknowledgments We wish to thank  B. Striepen  and  M. Cipriano ,  S. Lourido ,  D. Soldati-Favre ,  L. Sheiner ,  V. Carruthers ,  JF Dubremetz ,  W. Sullivan  and  P. Bradley  for their kind gift of cell lines, plasmids or antibodies. We also thank the " Montpellier Ressources imagerie " platform for providing access to their microscopes.
Work in S. B. 's laboratory is supported by a grant from  Agence Nationale de la Recherche  ( ANR-13-JSV3-0003 ) and core support from the  Fondation pour la Recherche Medicale  ( Equipe FRMDEQ20130326508 ) and the  Labex Parafrap (Agence Nationale de la Recherche)  ( ANR-11-LABX-0024 ). Work in F. T. 's laboratory is supported by grants from the  National Natural Science Foundation of China  ( 81672052 ), the  Zhejiang Natural Science Funds for Distinguished Young Scientists  ( LR17H190001 ) and Zhejiang Xinmiao talent plan (2017R413062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
For all these reasons, we report herein the characterization of the first virulent leptophages at the phenotypic, genomic, and proteomic levels. We also demonstrate that these leptophages use lipopolysaccharides (LPS) as a receptor on bacterial cells. A general analysis of LE3 and LE4 genomes did not reveal significant similarities with other viral genomes, suggesting they may constitute a new group of phages. We also searched for related prophages in Leptospira genomes available in public databases, leading to the identification of novel circular plasmids in a clinical isolate.
S4 ) probably due to the emergence of phages overcoming this resistance. RLE4, as well as the parent susceptible strain, were sequenced on an Illumina platform. Mutations that were detected in sequenced strains were mapped against the L. biflexa reference genome (Fig. 3C ). A single-nucleotide polymorphism (C->T at position 2,100,832) was identified. This mutation causes a premature stop codon in the gene LEPBIa2019 which encodes a probable acetyltransferase. This nonsense mutation leads to a truncated protein of 30 kDa instead of 37 kDa for the native protein. Attempts to complement RLE4 with wild-type LEPBIa2019 were unsuccessful (data not shown). Interestingly, LEPBIa2019 is located in the rfb/O-antigen locus of the LPS that could be part of a large operon. To confirm this initial observation, we generated a deletion mutant of LEPBIa2019 by allelic exchange in L.
Leptophage genome analysis. To date, the 73,622-bp genome sequence of the temperate phage LE1 is the only genome of a phage infecting Leptospira to be available in public databases  8. Here, we present the first complete genome sequences of lytic leptophages. The genomes of LE3 and LE4 are composed of 48,288 bp and 47,866 bp of double-stranded DNA, respectively, and have a GC content of 37. 3%; similar to that of L. biflexa (38. 6%) and LE1 (38. 5%). In total, the genome of LE3 and LE4 had respectively 83 and 81 ORF, with all the ORF on the same strand (Fig. 4 ). Whole-genome sequence alignments reveal that the phages LE3 and LE4 are closely related (95% identity at the nucleotide level and 78 shared ORF), but are genetically distinct from LE1 (Fig. 4 ). In terms of gene repertoire, LE3 has only four genes encoding hypothetical proteins that do not have clear homologues in LE4 while three genes, also encoding for hypothetical proteins, are predicted to be unique to LE4.