dataesr/scientific-paragraphs-categorization huggingface dataset:
Results Participant data collected from 230 patients between April 2006 and February 2009 were analysed. Patient characteristics are shown in Table  1. Patients were 47. 4 years of age on average. Eighty-seven percent of participants were male. The average duration of HIV infection was around 16 years and time since initiation of anti-retroviral therapy was 11. 2 years. Time since diagnosis of facial lipoatrophy was 5 years. Previous treatment of facial lipoatrophy was found in 39. 4% of patients (NEW-FILL W in 75% of cases). CD4 count was greater than or equal to 350 CD4/mm3 in 74. 5% of patients; almost 85% of patients had a viral load of less than 400 copies/ml and almost 60% had a viral load of less than 50 copies/ml. The most frequently observed combinations of antiretroviral agents were Data on 911 sessions of injections were collected on the 230 patients, i.
Furthermore, clinicians need not rely upon expensive and complicated diagnostic procedures and equipment to assess the need for patient intervention. In this study, the primary criterion to assess the impact of lipoatrophy was the subjective perception of patients. It can be seen that this criterion is extremely useful in the clinical assessment of need for lipoatrophy correction, and may be a better indicator of treatment need than medical assessment procedures commonly used in clinical trials such as DEXA scan, bioimpedance or sonography. For instance low sensitivity poses a problem for the use of sonography to detect LD in the clinical routine as a single exam  [24]. Treatment safety data concur with the findings of previous studies  [26] [27] [28] [29]. Immediate adverse events were reported by around 8% of patients, with ecchymosis, pain and skin redness being the most common.
Acknowledgements Grading of Photographs : Bruno Lalanne ,  Frédéric Mouly ,  Thierry Secchi. Additional Investigators :  Mojgan Bonarek ,  Jannick Chamberlin ,  Christophe Compagnon ,  Jacques David ,  Jacqueline Fabre ,  Reza Farhad ,  Karine Lacombe ,  Francoise Lucas ,  Frédérique Olivier-Masveyraud ,  Vlad Negulescu ,  Hervé Raspaldo ,  Michel Volstein.
To test for the presence of statistically significant (significance level < 0. 05) joinpoints and to estimate their value, we used the package "ljr" from the CRAN repository  [31]. In particular, the used function tests, based on the likelihood ratio test statistic, the null hypothesis of j joinpoint(s) versus the alternative of j + 1 joinpoint(s). The p-value is determined by a Monte Carlo method  [32]. We allowed for up to three possible joinpoints (j max = 3) and set as significance level < 0. 05). All the other statistical analyses were performed using STATA.
Acknowledgements The work reported was partly undertaken while  Dr Ronco  was hosted as Visiting Scientist by the  International Agency for Research on Cancer. Dr Baussano  is on leave from the  University of Piemonte Orientale, Novara, Italy. The research leading to these results has received funding from the  Italian Ministry of Health  ( L138/2004  project " NTCC Nuove tecnologie per lo screening del cervicocarcinoma ") and from the  European Community 's  Seventh Framework programme  ( FP7/2007-2013)  under grant agreement No. 242061  (acronym PREHDICT). The NTCC study was also financially supported by the  Regional Administrations of Piemonte, Toscana, Veneto  and  Emilia Romagna  and by the  Agenzia di Sanità Pubblica of Lazio. The funding sources did not have any role in the writing process of this manuscript.
In vivo caspase 3-positive cell quantification Immunohistochemical-stained slides were digitized using a Panoramic 250 Flash digital microscope (P250 Flash, 3DHisTech, Budapest, Hungary). Whole slides were scanned using brightfield scan mode with a 20X/NA0. 80 Zeiss Plan-Apochromat dry objective, and images were acquired with a two megapixel 3CCD color camera (CIS Cam Ref#VCC-F52U25CL, CIS Americas Inc. , Tokyo, Japan), achieving a 0. 22 mm/pixel resolution, corresponding to a Â 56. 09 magnification at the highest optical resolution in conventional microscopy. Panoramic Viewer and HistoQuant software were used for viewing and analyzing the digital slides, respectively (RTM 1. 15. 0. 53, 3DHisTech). A minimum of 12 annotations per slide covering 480% of the entire tissue were analyzed using the same profile file with the following characteristics: noise reduction (median filter strength ¼ 3), object definition (HSV: 44oHueo115, 36oSaturationo196, 5oVa-lueo250; filtering by size: valid objects415 mm 2 ) and object separation according to a 10-pixel distance between the center points of the two objects.
These settings allowed the automatic segmentation of the detected objects and the measurement of the number of detected objects per mm  2. Statistical analyses were performed on individual raw data using unpaired t-tests to compare the MAb-treated group to the PBS-treated group. Values are expressed as mean ± s. e. m. Po0. 05 were considered statistically significant. Collagen I detection by second-harmonic generation FL lymph nodes or cells were embedded in tissue-freezing media and frozen at À 80 1C. Then 5-mm sections were cut on a cryostat at À 20 1C. The slides were mounted in Fluorescence Mounting Medium (DAKO). Collagen detection was performed using a two-photon microscope 7MP upright microscope (Zeiss). Excitation light was provided by a Chameleon Ultra II Ti:Sapphire laser (Chameleon Ultra, Coherent Inc.
, Palo Alto, CA, USA) tuned to 830 nm. The average laser irradiation after the microscope objective was measured with an Ultracompact Laser Power Meter (New Focus Corp. , Irvine, CA, USA), which ranged from 0. 5 to 2 mW. The secondharmonic generation images were detected through a bandpass filter SP 485 (collagen emission, Semrock, Rochester, NY, USA). Images were acquired using a Â 40 oil immersion objective (NA ¼ 1. 4, Plan-Apochromat; Zeiss). All images were acquired with standardized conditions for gain and offset (brightness and contrast). Unprocessed images were analyzed using the Region Measurements function of the Metamorph software (Universal Imaging, Downingtown, PA, USA), which calculates the integrated fluorescence intensity for the entire image. For FL patient studies, institutional ethical approval from Inserm U1037 and informed consent were obtained in compliance with the Helsinki protocol.
ACKNOWLEDGEMENTS This study was supported by an institutional grant from the  INSERM, Canceropole Grand Sud-Ouest ,  INCA Pair Lymphome and Roche. We thank  Raphael Duran ,  Marie-Noelle Paludetto  ( CRCT, INSERM UMR1037 ) for performing preliminary experiments,  Amandine Blanc  ( CRCT, INSERM UMR1037 ) for technical assistance Sophie Allart and  Astrid Canivet  ( Imaging core Facility, CPTP, INSERM U1043, Toulouse, France ) and  Maryline Calyse  ( ANEXPLO/CREFRE, Service de Zootechnie, Toulouse, France ). We thank  Scientific Scripts  (http://www. scientificscripts. com/)for English proofreading. Trastuzumab (TTZ, Herceptin), Rituximab (RTX, Mabthera) and Obinutuzumab (GA101) were provided by  Genentech (San Francisco, USA) ,  Roche  ( Boulogne Billancourt, France ) and  Roche Glycart (Schlieren, Switzerland) , respectively.
Histopathological analysis One week after hemodynamic studies, mice were killed by cervical dislocation; hearts were collected at dedicated time points. Each heart's weight was measured and normalized with body weight or with tibia length, in order to minimize variations. Organs were fixed in Finefix (Milestone medical, Italy), paraffin embedded and cut into 4 mm sections. Cross sections were taken from the midventricular plane of the heart, and from the plane between the mid-ventricle and base of the heart. Sections were stained with Hematoxilin-Eosin-Saffranin (HES), Sirius Red (SR) and examined using conventional light microscopy and quantified using HISTOLAB software.
In the present study, long-term maintenance of overall cardiac physiological function was observed after low dose irradiation, with alterations scored as Class I by the International Small Animal Cardiac Health Council (ISACHC). However, mild decreased ejection fraction (EF) and shortening fraction (FS) were seen, consistent with clinical data  [5]  and with other in vivo experimental data  [30, 31]. These observations are not consistent with other experimental reports obtained in rats and mice after exposure to high dose of ionizing radiation and in which increase in EF and SF was shown  [32] ;  [33]. The significance of this discrepancy between the effect induced by high and low doses of irradiation remains to be investigated but in any case, the reported variation remains in the physiological range, suggesting occurrence of compensatory mechanisms.
Acknowledgments We thank  Olivia Bawa  and  Benoit Petit  for excellent technical assistance in histology and IGR-SCEA for animal care. We thank  Pr MJ McKay  for critical reading of the MS and English edition. We thank the  Department of LIPA  for the use of ultrasonographic system (Aplio, Toshiba). Inserm  U1030  is a member of the  Laboratory of Excellence LERMIT  supported by a grant from  ANR  ( ANR-10-LABX-33 ).
Statistical Analysis Statistical analyses were performed by using the Statcalc module of Epi Info 3. 5. 3 (Centers for Disease Control and Prevention, Atlanta, GA, USA) to calculate the χ 2 values for the incidence rate trends calculated for each country. PASW Statistics software 17. 0 (IBM, SPSS Inc. , Armonk, NY, USA) was used to perform Pearson correlation analyses. The relative risk (RR) and the 95% CI of the risk were calculated by using either the Mantel-Haenszel χ 2 test or Fisher's exact test. The statistical significance of the χ 2 values was evaluated at α = 0. 05. The attack rates of R. felis infection and malaria were calculated for each country, site, sex, and age range. In contrast, the incidence rates of R. felis infection and malaria for S 1-2 were calculated monthly and yearly from June 13, 2010 through October  13, 2011.
Acknowledgments We thank the villagers who participated in this study. We also thank  Masse Sambou ,  Aliou Diallo ,  Khadim Leye ,  Babacar Ndao ,  Malick Diop ,  Arsène Mabika ,  Marielle Bedotto ,  Denis Pyak  and  Annick Bernard  for technical support. This study was funded by the  Agence National de Recherche  grant  2010  (MALEMAF),  Foundation Mediterranée Infection, Fondation Mérieux , and a collaborative grant to  Josselin Thuilliez ,  University of Paris, Paris, France. Dr Mediannikov  is an infectious disease specialist and research scientist working at the  Unit of Research on Emergent Infectious and Tropical Diseases in Marseille, France and Dakar, Senegal. His main research interests include vector-borne diseases and medical entomology. Dr Socolovschi  is a physician of infectious diseases and tropical medicine at the  Medical School of Marseille, France.
3547), anti-RAB7 (No. 9367), anti-RAB8 (No. 6975), anti-RAB9 (No. 5118), anti-RAB11 (No. 5589) and anti-EEA1 (No. 3288). Non-targeting (NT) shRNAs in the MISSION RNAi pLKO. 1-puro vector were obtained from Sigma-Aldrich. Several shRNA sequences targeting rat PC1/3 (accession number NM_017091) were tested. TRC sequences for shRNAs against human and mouse PC1/3 were modified to target the rat PC1/3 sequence using the Addgene pLKO shRNA design recommendation (see web link below). The most effective sequence used in this paper was 59-AATTAT-GACCCAGAGGCTAGC-39, which targets 21 nucleotides start-ing at position 757 in the gene and corresponds to a modified version of TRCN0000032922. This sequence was cloned into the pLKO. 1 vector using the protocol available at http://www. addgene. org/tools/protocols/pLKO/.
Confocal Microscopy and Co-localization The NR8383 cells were grown in culture flasks on coverslips and stimulated as described in text. The cells were treated and observed with an Olympus FV1000 inverted confocal laserscanning microscope as previously described with minor modifications to the protocol  [34]. Primary antibodies were incubated in a moist chamber overnight at 4uC. Coverslips were mounted with SlowFade Gold Antifade Reagents (Life Technologies). Olympus Fluoview software (version 1. 6b) was used for image acquisition. The images were further processed and analyzed using ImageJ  [35, 36]  with Bio-Formats plugin  [37]. Statistical analysis was performed using GraphPad Prism 5 software.
ELISA Cells were plated at densities of 2. 5610 5 or 5610 5 cells/ml in serum-free F12K medium overnight at 37uC in a humidified atmosphere containing 5% CO 2. The medium was subsequently changed, and the cells were stimulated with vehicle or 100 ng/ml LPS without serum for the indicated times. The medium was collected and cleared of cells and cell debris by centrifugation at 800 g for 5 min. Cytokines were measured using ELISA kits specific for rat TNF-a (BD biosciences), IL-1b and IL-6 (R&D Systems) according to the manufacturers' instructions. Statistical analysis was performed using GraphPad Prism 5 software.
PC1/3 and Most Common TLRs are Expressed in NR8383 Cells Although various macrophage cell lines are available, little information was available regarding their PC1/3 expression. The human macrophage cell line THP-1 was shown to express PC1/3, however, THP-1 cells need to be stimulated with phorbol 12myristate 13-acetate (PMA) to induce PC1/3 expression  [10]. We have screened various cell lines and discovered that NR8383 cells, originally derived from rat alveolar macrophages  [32, 33] , express PC1/3 but not PC2 (Figure  1B ). We confirmed that the resulting RT-PCR product was PC1/3 by sequencing (sup. data Figure  S1 ). This observation agrees with previous data obtained using isolated rat alveolar macrophages and splenic macrophages  [11]. Moreover, NR8383 cells were shown to be sensitive to TLR ligands, notably LPS  [24]  and polyI:C  [41] , making them a good cellular model in which to examine the role of PC1/3 in TLRbased activation of macrophages.
When we quantified the integrated optical densities of EEA1 and RAB5 (pixel intensity x area), we observed no significant difference between NT shRNA and PC1/3 shRNA. This means that the overall cellular signals are comparable. However, mean pixel intensities for EEA1 were lower in PC1/3 shRNA than NT shRNA cells (4263 vs, 6668, respectively, p = 0. 009 Student's t-test). In addition, there was an increased peripheral labelling in PC1/3 shRNA compared to NT shRNA cells (3366% vs 2264%, respectively, p = 0. 01 Student's t-test). Together these data are indicative of a broader distribution of EEA1 labeled endosomes, but also of their closer proximity to the PM. We also verified tested the expression levels of EEA1 (Figure  8A ) and RAB5 (Figure  8B ) by western blotting and observed an increase in EEA1 expression but a decrease in RAB5 expression.
Acknowledgments We are grateful to  Drs. Marc Pallardy  ( CEA, Paris ) and  Sandrine Lacour  for providing the NR8383 cell line used in this study, to  Dr. Christine Lavoie  ( UdeS, Sherbrooke ) for providing material and assistance for confocal microscopy and to  Christian Slomianny  ( UniversiteLille 1 ) for electronic microscopy.
Cell treatment DC were cultured during 18 hours in the presence of several concentrations of Ca 2+ as following; RPMI at 0. 4 mM, RPMI with BAPTA 10 mM to obtain Ca 2+ free solution, RPMI with CaCl 2 2 mM and RPMI with CaCl 2 4 mM. TLR agonists (LPS (50 ng/ml), zymosan (25 mg/ml) and TNF-a (20 ng/ml)) as well as Ca 2+ inhibitors such as Thapsigargin (750 nM), D609 (100 mM) and 2-APB (100 mM) were added directly to immature DC for 18 hours in individual wells. All drugs and chemicals were purchased from Sigma-Aldrich (St Quentin Fallavier, France). Cells were harvested, washed and used for analyses in flow cytometry, mixed culture reaction or spectrofluorometric analysis. For reagents suspended in dimethyl sulfoxide (DMSO), an equal volume of DMSO was added to control cultures. At the concentrations used, DMSO has no inhibitory or stimulatory effects on DC (data not shown).
Excitation light at the two-excitation wavelengths maxima of Fura-2 (340/380 nm) was chopped by a monochromator (Cairn Optoscan, UK). The excitation protocol was a 50 ms excitation at each wavelength every 2 s. Excitation light was directed through a 606 oil immersion objective with a numerical aperture of 1. 4 (Nikon Plan Apo, France). Fluorescence emissions at 510620 nm were detected by a photomultiplier tube (PMT) placed on the side of the microscope. The analogical signals of PMT were digitized by a Digidata 1322, a converter (Axon Instrument, USA) at a sampling frequency of 2 kHz. This numeric signal was analyzed using Clampex 8. 2 (Axon Instrument, USA). Background fluorescence was determined at 340 and 380 nm from an area of the dish free of cells after experiment and was routinely subtracted.
Flow Cytometric Analysis Dendritic cells were incubated at 4uC with saturating concentrations of fluorochrome-conjugated mAbs (CD80, CD86, CD83, CD25, HLA-DR and DC-SIGN) in the dark for 30 min, washed twice with PBS, fixed in 0. 5% PFA-PBS solution and analyzed with a FACSCanto (Becton Dickinson, France). Dead cells were gated out on the basis of their light scatter properties. Data were analyzed with Diva Software. For intracellular detection of IFN-c, cells were incubated in Golgistop solution (Becton-Dickinson) for the last 5 hours of culture; next the cells were permeabilized with BD cytofix/ cytoperm solution (Becton-Dickinson, France) and finally labeled with an APC-coupled antibody specific for IFN-c (Becton-Dickinson, France) according to the manufacturer's instructions.
Statistical analysis Statistical analyses were performed using a nonparametric Mann -Whitney test with XLSTAT 2007 software. For all tests, a p-value of ,0. 05 was considered statistically significant. B ) and IFN-c (panel C) were measured in supernatants of DC treated by maturating agents (TG (750 nM), LPS (50 ng/ml), zymosan (25 mg/ml) or TNF-a (20 ng/ml)) for 18 h in the presence of 100 mM 2-APB. In each graph, the black line represents the mean of 7 experiments, (*p,0,05). doi:10. 1371/journal. pone. 0061595. g004.
Acknowledgments Authors wish to thank the  Etablissement Francais du Sang du Centre Atlantique of Tours  for providing blood samples from healthy donors,  Professor M. HOTH  ( Saarland University ),  Doctors F. ROUSSEL  ( Facultes Universitaires Notre-Dame de la Paix, Namur ),  Prof. D. ANGOULVANT  ( Tours University ) and T. DOMANSKI ( AACC, Arnold, MD ) for helpful discussion and English revision of the text.
Acknowledgements We are grateful to  G. Brownlee  for providing the original plasmids for the influenza type A virus reverse genetics system and  R. Frade  ( Saint Antoine Hospital, Paris, France ) for the SK 93/2 cells. We thank  D. Marc  ( INRA, Tours, France ) for anti-NS1 polyclonal antibodies,  V. Frigard  for technical assistance,  D. Marc ,  G. Abou-Jaoudé ,  D. Moisy  and  S. Munier  for helpful discussions and critical reading of the manuscript.
Background-The Immune Epitope Database (IEDB), originally focused on infectious diseases, was recently expanded to allergy, transplantation and autoimmunity diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We utilize a combined tutorial and metaanalysis format, which demonstrates how common questions, related to diabetes epitopes can be answered. Results-A total of 409 references are captured in the IEDB describing >2,500 epitopes from diabetes associated antigens. The vast majority of data were derived from GAD, insulin, IA-2/ PTPRN, IGRP, ZnT8, HSP, and ICA-1, and the experiments related to T cell epitopes and MHC binding far outnumbers B cell assays. We illustrate how to search by specific antigens, epitopes or host. Other examples include searching for tetramers or epitopes restricted by specific alleles or assays of interest, or searching based on the clinical status of the host.
BACKGROUND The present study illustrates how the Immune Epitope Database and Analysis Resource (IEDB), originally focused on infectious diseases  [1] , can be used to analyze epitope data related to type 1 diabetes (T1D) chosen as an exemplary disease. A combined tutorial and meta-analysis format demonstrates how common questions related to diabetes epitopes can be addressed using the IEDB and then also discusses the results of these queries. T1D is characterized by autoimmune-mediated destruction of insulin-producing pancreatic beta cells, leading to insulin deficiency. CD4 + and CD8 + T cells have been implicated in T1D pathogenesis  [2] , and islet cell antibodies are diagnostic markers of disease. Mapping of diabetes associated auto antigens and epitopes enables the development of diagnostics to monitor beta cell autoimmunity and the design of novel immunoregulatory therapeutics  [3, 4].
Epitope data captured relates to either well defined minimal/optimal epitopes, or larger and less well-defined epitope-containing regions (20-50 residues), and "partial epitopes" including amino acid residues within epitopes identified as key for binding to immune receptors. Molecular structures that were tested for immune recognition but found to be unreactive are also reported as "negatives. " Epitope reports can be subject to experimental biases and limitations, which may in turn result in the perpetuation of certain biases in the literature. The assay-centric nature of the IEDB was designed to support the scientific community, representing the data globally (analogous to Pub-Med) without arbitrary value judgments, but simultaneously providing a platform for selective inquiry and analysis.
Commonly reported diabetes-associated antigens To identify diabetes associated antigens, we compiled the proteins which were the source of epitopes characterized in the references described above, removing proteins not derived from mammals, as they were sources as experimental controls (such as peptides from influenza). We next analyzed the nature of epitopes described for the most frequently reported antigens. For example, entering 'GAD' in the Molecule Finder we generate a list of available records for individual GAD entries (including all isoforms) (Figure  1A ). The first entry in this list, 'glutamate decarboxylase 1 isoform GAD67, PROTREE [PT10001739], Homo sapiens' represents the high node on the Protein Tree for all human GAD proteins. The Protein Tree is a unique feature developed by the IEDB which organizes individually curated GenBank entries by sequence homology and thereby allows gathering of related records.
To date, 305 structures associated with positive data (epitopes) are reported from a total 127 references. Human GAD epitopes were defined in several host species including, human, mouse and rabbit. T cell assays outnumber B cell assays by nearly 4 to 1. While a relatively high number of MHC binding records are available, only 2 positive ligand elution assays were reported. Records associated with related antigens (e. g. mouse GAD) can also be queried directly using the Protein Tree feature, accessible through the IEDB Molecule Finder [use 'Highlight in Tree']. Because the Protein Tree is organized by species, if different species (ex. mouse or rat) are considered, separate queries for each must be performed. Figure  1B  also shows the Protein Tree highlighting mouse GAD. Detailed data can be retrieved from the results summary table (Figure  1 ), by clicking on blue values that represent live links.