dataesr/scientific-paragraphs-categorization huggingface dataset:
Patient Population This study is an observational case-control study performed at the University Hospital of Bordeaux. Fifty patients with POAG (20 men, 30 women, mean age 61. 9 +/-6. 9 years) and 50 age-and sex-matched controls (20 men, 30 women, mean age 61. 9 +/-7. 0 years) were prospectively included. This research followed the tenets of the Declaration of Helsinki. Participants gave written consent for the participation in the study. The design of this study was approved by the Ethical Committee of Bordeaux (Comité de Protection des Personnes Sud-Ouest et Outre-Mer III) in March 2012. This study was registered on the website http://clinicaltrials. gov/ (identifier NCT01621841).
Measurement of DTI metrics along the optic radiations From the DTI data, the distortions induced by eddy currents were first corrected, then a diffusion tensor model was fitted at each voxel using Olea Medical ® software to generate fractional anisotropy (FA) maps and to investigate the microstructural integrity of the optic radiations. The optic radiations were identified using deterministic tractography between two seed-regions of interest (ROIs) over the proximal and distal optic radiations according to previously published method and landmarks  29. The proximal ROI was placed near the lateral geniculate nuclei, while the distal ROI was placed just anterior to its termination in the visual cortex. Fiber tract propagation was terminated for FA<0. 2 and angle<35° based on agreed-upon thresholds.
DTI could represent a future way to explore central nervous system of glaucomatous subjects, leading to a better understanding of the pathophysiology and, potentially, to help clinical trials evaluate new therapeutic strategies based on neuroprotection or brain repair. Green boxes are the markers placed manually on anterior and posterior parts of the optic radiations. Green lines are optic radiations automatically reconstructed by the Olea Medical ® software. Red boxes are markers manually placed to manually deleted fibers outside the expected area.
Gene expression analysis by quantitative PCR Real-time qPCR was performed in a Light Cycler 480 (Roche Diagnostics, Risch, Swiss) using the LC FastStart DNA Master SYBR Green I kit (Roche Diagnostics). Amplification was initiated with an enzyme activation step at 95°C for 10 min, followed by 40 cycles consisting of 20s of denaturation at 95°C, 15s of annealing at the temperature appropriate for each primer, and 10s of elongation at 72°C. Primers used to amplify cDNA are listed in Table  1. Data were analyzed using LC 480 Software (Roche Diagnostics). The relative genes expression were normalized to the GAPDH reference gene.
They were covalently linked with fluorescein isothiocyanate (FITC) or indodicarbocyanin (Cy5) at the 5 0 -end (Thermo Fischer Scientific GmbH, Ulm, Germany). All the following steps were performed in the dark, a volume of 150 μl of hybridization solution was added to each well and cells were pelleted at 4000g for 15 min. Non-specific binding of the probe was removed by incubating the bacterial cell suspension at 37°C for 20 min in a washing solution (64 mM NaCl, 20 mM Tris-HCl, pH 8. 0, 5 mM EDTA, 0. 01% SDS). Cells were pelleted and resuspended in phosphate-buffered saline (PBS, pH 7. 2). Aliquots of 100 μl were added to 0. 5 ml of FACS Flow (Becton Dickinson, Franklin Lakes, New Jersey) for data acquisition by flow cytometry. Cell enumeration was performed by combining one group Cy5-probe with the Eub338 FITC-probe in one hybridization tube.
Methodology We have been conducting sociological research into the Calanques National Park since 2008. This began in the context of two research programmes, one focused on the consultation process surrounding the creation of the park  (Deldrève and Deboudt, 2012)  and the other interested in land-and sea-based uses of the territory of the future park  (Tatoni et al. , 2013)  (Figure  1 ). This paper is based on a corpus that combines data collected during direct observation and from a qualitative survey (using semi-structured interviews). Between 2008 and 2012, we observed thirty-two dialogue meetings and conducted two hundred and thirty interviews with managers, experts, actors from the non-profit sector, and participating and non-participating users of the Calanques and surrounding islands.
Among the users interviewed who did not participate in the consultation process, 125 were met directly onsite, primarily in one land-based area and three sea-based locations. The chosen land area -the Marseilleveyre massif between the Mont-Rose and Marseilleveyre Calanques -is one of the entry points into the Calanques closest to Marseille. The first sea-based location is a popular diving spot called Les Farillons, within the Riou archipelago. The second is Sormiou Bay, the largest natural anchorage area in the Calanques, famous among yachters; the third location is a natural anchorage zone in the Frioul archipelago particularly near the main town harbours. We recorded the interviews and meetings, and all interviews were transcribed. We then thematically analysed this data-set manually and using nVivo© software.
The second principle required the representation of a majority of users and activities from the sites. In keeping with these procedural norms, members of the GIP managerial team specifically identified groups of people who appeared most organized and legitimate. As a result, the aforementioned recreational users of the Calanques -who are both active and resourceful -were essentially first in line. When the National Park was created, there were no recent data on the types of people that visit the Calanques. Thus, the wide variety of social backgrounds of such visitors and the diverse activities they take part in were not identified as part of the dialogue process. Further, no effort was made to redress the imbalance caused by the overwhelming presence of certain users in this process. This same group, whose leaders belonged to both user and resident organizations, did not shy away from exerting their influence.
Using manual curation based on the known biological, physiological or functional relevance to the disease of the candidate genes, we were left with a single homozygous variant in the PIK3R4 gene, named herein VPS15: p. Arg998Gln, c. 2993G4A, Chr3:(GRCh37):g. 130422672C4T. The variant and its cosegregation with the phenotype in the family was confirmed by Sanger sequencing. Overall, deleterious or potentially pathogenic homozygous or compound heterozygous variants were not found in 382 patients with presumed ciliopathy and yet unknown molecular origin (our databases and the databases of three laboratories specialized in ciliopathies and other rare genetic diseases) and in 7,360 patients screened for other rare diseases (Institut IMAGINE). The PolyPhen-2 (polymorphism phenotyping v2) software, a tool analysing impact of amino acid substitutions on protein structure and function  13  , predicts that this R998Q substitution is 'probably damaging' with a HumVar score 0.
Nowadays, new ciliopathy causative genes are very likely to be identified in very few if not unique families. One explanation could be that the gene involved may code for an essential protein for which only a very limited number of mutation sites may be tolerated, the remaining mutational sites being probably lethal. Here, we report the first family with a missense mutation in the VPS15/PIK3R4 gene. In metazoan (mouse and Drosophila), VPS15 is an essential gene  11, 12. The R998Q substitution is predicted to be probably damaging by the PolyPhen-2 programme  13. Indeed, arginine is a positively charged polar amino acid, frequently involved in saltbridges and important for protein binding sites. Thus, a change from an arginine to a glutamine that is polar and uncharged is certainly not neutral.
Variant filtering was performed with the VaRank programme 36 using stringent criteria excluding (i) non-pathogenic variants defined in dbSNP 138, (ii) variants represented with an allele frequency of more than 1% in dbSNP, the Exome Variant Server, the Thousand Genomes Project Catalog and the ExAC database, (iii) variants found in the homozygous state or more than once in the heterozygous state in 70 control exomes, (iv) variants into 5 0 -UTR (untranslated region), 3 0 -UTR, downstream, upstream or intron locations without local splice effect prediction, (v) synonymous variants without local splice effect prediction. This step reduced the number of genetics variants to 1,085, 793, 1,124 and 2,009 variants, respectively, per proband (Supplementary Table  1 ). The variant and its cosegregation with the phenotype in the family was confirmed by Sanger sequencing.
The cilia length from the base to the tip was measured using the ImageJ program on confocal images, and the length of each primary cilia was determined for 120 to 200 cells per sample (ctrl1, ctrl2, ctrl3, II. 1, II. 3, II. 5 and BBS4 À / À ). Transient transfection for GFP-2XFYVE HRS and VPS15-HA plasmids. The fibroblasts cells were cultured to be 60% confluent the day of transfection in Nunc Lab-Tek chamber slides (Thermo Scientific). Five hundred nanograms of plasmid was transfected using the DNA transfection reagent (jetPEI, Polyplus transfection) according to the protocol for adherent cells. After 24 h, the fibroblast cells were washed three times in PBS, then the cells were fixed for 30 min at room temperature with 4% paraformaldehyde, rinsed three times in PBS for 5 min each, stained with DAPI and confocal fluorescence microscopy was done.
Acknowledgements We warmly thank the members of the family for their participation. We thank  J. L. Mandel  and the financial support of the  Centre Regional de Genetique Medicale de Strasbourg  and the  Caisse d'Assurance Retraite et de la Santeau Travail Alsace-Moselle. We also thank  RETINA France  ( 100 Exomes Program ) and FORMICOEUR for their constant and strong support. We thank the teams of  Professor N. Katsanis  and  Dr E. Davies  ( Duke University, USA );  Professor F. Hildenbrandt  ( Howard Huges Medical Institute and Harvard Medical School, USA ) and  Dr J. M. Rozet  ( Fondation Imagine, France ) for sharing data from their ongoing sequencing programs. We thank  D. Klionsky  ( University of Michigan, USA ),  H. Riezman  ( University of Geneva, Switzerland ) and  H. Stenmark  ( Oslo University Hospital, Norway ) for sharing strains and antibodies.
We thank  B. Rinaldi ,  D. Stuber  and  L. Kuhn  ( CNRS/UDS, Strasbourg, France ) for technical help and  R. Poncelet-Bach  for schematic representation of cilia trafficking. This work was funded by  INSERM  (to H. D. and S. B. ),  CNRS  (to S. F. ),  Universitede Strasbourg  (H. D. , S. F. and IDEX 2015 Attractiviteto S. B. ),  Agence Nationale de la Recherche  ( ANR-13-BSV2-0004  to S. F. ) and  AFM-Telethon  ( AFM-SB/CP/2013-0133/16551  to S. F. ). The mass spectrometry instrumentation was granted from  Investissement d'Avenir program  (NetRNA  ANR-10-LABX-36 ). The zebrafish work (C. E. and U. S. ) was funded by  Deutsche Forschungsgemeinschaft , ( DFG Str439/5-1  and  DFG RO2173/5-1 ) and  Bundesministerium fur Bildung und Forschung  ( 01ZX1407A ).
Introduction As previously described in mAbs, a debate is in progress regarding whether the nomenclature of therapeutic antibodies would be based henceforthor noton the percentage of nucleotide sequence identity between the genomic DNA encoding the variable regions of a given antibody and the closest human variable gene sequence in the international ImMunoGeneTics information system Ò (IMGT Ò ) database. 1  The International Nonproprietary Names (INN) are assigned by the World Health Organization (WHO) and, up to now, for monoclonal antibodies that have been more or less humanized (hereafter called "recombinant antibodies" for simplification), WHO has distinguished chimeric (-xi-), humanized (-zu-) and fully human (-(m)u-) antibodies,  2  based on the genetic origin of the variable domains of the antibody.
Acknowledgments and disclosures This work was supported by the  French Higher Education and Research Ministry  under the program " Investissements d'Avenir " grant agreement:  LabEx MAbImprove   ANR-10-LABX-53-01. We thank  Dr. Paul Parren  and  Dr. Alain Beck  for their helpful comments. The authors declare no competing financial interests that are directly relevant to the content of this article.
Introduction The pooled or meta-analysis of regional brain volumes derived from T1-weighted MRI data across multiple sites is reliable when data is acquired with similar acquisition parameters  [1, 2, 3]. The inherent scanner-and sequence-related noise of MRI volumetrics under heterogeneous acquisition parameters has prompted many groups to standardize protocols across imaging sites  [1, 4, 5]. However, standardization across multiple sites can be prohibitively expensive and requires a significant effort to implement and maintain. At the other end of the spectrum, multisite studies without standardization can also be successful, albeit with extremely large sample sizes. The ENIGMA consortium, for example, combined scans of over 10,000 subjects from 25 sites with varying field strengths, scanner makes, acquisition protocols, and processing pipelines.
The remaining ROIs are reported in the supplemental materials. Test-retest reliability, defined as ICC(1,1)  [35] , was computed across each site and protocol for the selected metrics using the "psych" package in R  [36]. The between-site ICC(2,1) values were computed following the procedure from previous studies on multisite reliability  [35, 1]. Variance components were calculated for a fully crossed random effects model for subject, site, and run using the "lme4" package in R. Using the variance components, between site ICC was defined as  (12)  and an overall within-site ICC was defined as  (13)  Scaling factors between sites were estimated using ordinary least squares from the average of the scan-rescan volumes, referenced to average scan-rescan volumes from the UCSF site. The OLS was run with the intercept fixed at 0.
Scaling Factor Validation Scaling factor estimates were validated under the assumption of scaled, systematic error, in 2 ways: first, by simulating power curves that take into account the uncertainty of the scaling factor estimate, and second, by a leave-one-out calibration. For the simulation, we generate data for each of the 20 sites included in this study. Subcortical gray matter volumes (scGMV) for each site were generated for two subject groups based on a small standardized effect size (Cohen's d) of 0. 2, which reflects the effect sizes seen in genomics studies. Age and gender were generated as matched covariates, where age was sampled from a normal distribution with mean and standard deviation set at 41 and 10 years, respectively. Gender was sampled from a binomial distribution with a probability of 60% female to match typical multiple sclerosis cohorts.
Coefficients were set on the intercept as 63. 135 cm 3 , β 10 as -. 95 cm 3 , covariates Z Age as -. 25 cm 3 /year and Z Gender as 4. 6 cm 3. scGM volumes were generated in a linear model using these coefficients and additional noise was added from the residuals, which were sampled from a normal distribution with zero mean and standard deviation 5. 03 cm 3. Next, the scGM volumes were scaled by each site's calculated scaling factor and gaussian noise from the residuals of the scaling factor fit of that particular site were added. (15)  The simulated dataset of each individual site was modeled via OLS, and an F score on X Group was calculated following our proposed statistical model:  (16)  A power curve was constructed by running the simulation 5000 times, where power for a particular p-value was defined as the average number of F values greater than the critical F for a set of false positive rates ranging from 1e -4 -1e -2.
In  [44] , researchers developed a method to more accurately estimate partial volume effects using only T1-weighed images from the ADNI dataset. This approach resulted in higher classification accuracy between Alzheimer's disease (AD) patients and mild cognitively impaired (MCI) patients from normal controls (NL). Designing optimized pipelines that are robust for each site, scanner make, and metric, is outside the scope of this paper. However, Kim and colleagues have developed a robust technique for tissue classification of heterogeneously acquired data that incorporates iterative bias field correction, registration, and classification  [45]. Wang and colleagues developed a method to reduce systematic errors of segmentation algorithms relative to manual segmentations by training a wrapper method that learns spatial patterns of systematic errors  [46].
Methods such as those employed by Wang and colleagues may be preferred over standard segmentation pipelines when data acquisition is not standardized. Due to its wide range of acquisition parameters and size of the dataset, our approach could be used to evaluate such generalized pipelines in the future. The above derivation of power for a multisite study defines hard thresholds for the amount of acceptable scaling factor variability (CV a ) using scaled, systematic error from MRI. Many factors contribute to the CV a cut-off, such as the total number of subjects, total number of sites, effect size, and false positive rate. In Figure  7 , we show the distribution of experimental CV a values across all Freesurfer aseg ROIs to reference while comparing power curves of various sample sizes. The maximum CV a value is 9% which, with enough subjects and sites, falls well below the maximum acceptable CV a value.
Alternatively, multisite studies employing our approach can use the results of our direct-volume calibration (the estimates of CV a for each ROI) to estimate sample sizes based on our proposed power equation and bias measurements without acquiring their own human phantom dataset to use in calibration. To our knowledge, this is the first study measuring scaling factors between sites with nonstandardized protocols using a single set of subjects, and deriving an equation for power that takes this scaling into account via mixed modeling. This study builds on the work of  [31] , which investigated the feasibility of pooling retrospective data from three different sites with non-standardized sequences using standard pooling, mixed effects modeling, and fixed effects modeling. [31]  found that mixed effects and fixed effects modeling outperformed standard pooling.
The equation for power we outlined in this study along with our measurements of variability between sites should help researchers undestand the trade-off between protocol harmonization and sample size optimization, along with the choice of outcome metrics. Our statistical model and bias measurements enables collaboration between research institutions and hospitals when hardware and software adaptation are not feasible. We provide a comprehensive framework for assessing and making informed quantitative decisions for MRI facility inclusion, pipeline and metric optimization, and study power. Vlaanderen). AG and BD are supported by the Research Fund KU Leuven (OT/11/087) and the Research Foundation Flanders (G0A1313N). MRI acquisitions in Hospital Clinic of Barcelona were funded by a "Proyecto de Investigación en Salut" grant (PI15/00587.
Acknowledgments We thank the study participants, MR technicians, and acknowledge  Stephane Lehéricy ,  Eric Bardinet ,  Frédéric Humbert  and  Antoine Burgos  from the  ICM IRM facility (CENIR)  and the  CIC Pitié-Salpêtrière  for their expertise. Funding was provided by  R01 NS049477. Additional support was provided by  ICM F-75013 Paris, INSERM  and  IHU-A-ICM  ( ANR-10-IAIHU-06 ). BD is a Clinical Investigator of the  Research Foundation Flanders (FWO-.
ACKNOWLEDGMENTS This study was supported by  INSERM ,  Joint Transnational Call 2011 for "Integrated Research on Genomics and Pathophysiology of the Metabolic Syndrome and the Diseases arising from It" from l ' Agence Nationale de la Recherche (ANR) of France (PLT) ; the  Lefoulon-Delalande Foundation ; and the  Francophone Diabetes Society  (to OL). This study was further supported by the  German Research Foundation (DFG) :  CRC 1140  (to TBH) and  CRC 992  (to TBH),  Heisenberg program  (to TBH) and  HU 1016/8-1 ; by the  European Research Council-ERC  grant  616891  (to TBH) and grant  311255  (to PLT); by the  BMBF-Joint transnational  grant  01KU1215  (to TBH) and  STOP-FSGS 01GM1518C  (to TBH); by the  Else-Kröner Fresenius Stiftung-NAKSYS ; and by the  Excellence Initiative of the German Federal and State Governments (GSC-4, Spemann Graduate School  and  EXC294 ,  BIOSS II  to TBH).
We evaluated EuroTravNet (a GeoSentinel subnetwork) data from June 2013 to May 2016 on 508 ill travellers returning from Brazil, to inform a risk analysis for Europeans visiting the 2016 Olympic and Paralympic Games in Brazil. Few dengue fever cases (n = 3) and no cases of chikungunya were documented during the 2013-15 Brazilian winter months, August and September, the period when the Games will be held. The main diagnoses were dermatological (37%), gastrointestinal (30%), febrile systemic illness (29%) and respiratory (11%). We analysed travel-associated morbidity in ill travellers returning from Brazil and presenting at 22 EuroTravNet sites during June 2013 to May 2016. As the Olympic and Paralympic Games will take place during August and September, the cooler months in Brazil, we focused on the main vector-bone diseases reported during these months.
EuroTravNet and study inclusion criteria EuroTravNet, a subnetwork of GeoSentinel  [1] , comprises 22 European sites specialised in travel or tropical medicine that report clinician-based data on ill travellers  [2]. Sites enter anonymised data on demographics, travel history, reason for travel, pre-travel advice, hospitalisation, major clinical symptoms and final, clinician-verified diagnoses. In our study, only travellers with Brazil as a single country of exposure were included. Only confirmed and probable diagnoses were included and patients whose only travel was for 'migration' were excluded. Every patient had at least one diagnosis (from a list of 556 possible diagnostic codes). Diagnoses were based on the recognition of a specific causative pathogen using the best reference diagnostic tests available.
Background International mass gatherings pose a risk for communicable disease outbreaks and onward rapid, global spread of infection  [3]. The Olympic Games will take place mainly in Rio de Janeiro, Brazil, on 5-21 August 2016, followed by the Paralympic Games, on 7-18 September 2016. More than 400,000 visitors to the Games are expected  [4]. The European Centre for Disease Prevention and Control (ECDC) recently issued a health risk assessment for European citizens visiting the Games  [5] , based mainly on extrapolation of data obtained from the Brazilian population. Data on illness in travellers returning from Brazil will provide additional information on which to base an accurate risk assessment for Europeans attending the Games. A previous study on this topic was conducted by GeoSentinel (the Global Surveillance Network of the International Society of Travel Medicine) among travellers to Brazil between July 1997 and May 2013  [6].
Study Population and Follow-up for Cancer Incidence Detailed information on the study design, rationale and methods of the EPIC study, including assessment of diet and lifestyle factors, has been described previously  (17, 18). Briefly, between 1991 and 2000 more than 520,000 men and women aged 20-85 years were recruited in 23 centres throughout 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom). At recruitment, standardised dietary, lifestyle and socio-demographic questionnaires including information on physical activity, education, smoking, medical history and anthropometric data were collected. Blood samples were collected from participants at recruitment, immediately processed and fractionated into plasma, serum, white blood cells and red blood cells.