dataesr/scientific-paragraphs-categorization huggingface dataset:
A. S. is a postdoctoral fellow of the Fund for Scientific Research Flanders (FWO,  12G3616N ). H. S. is a PhD fellow of the Fund for Scientific Research Flanders (FWO,  1125416N ). K. H. was funded by the  Agency for Innovation by Science and Technology, IWT. J. -S. L. and H. K. G. were funded by  Global Frontier  project of the  National Research Foundation of Korea  ( NRF-M3A6A4-2010-0029785 ),  National Research Council of Science & Technology (NST)  grant of the  Korea government (MSIP)  ( CRC-15-04-KIST ), and  KRIBB   Research Initiative Program. F. D. was supported by a grant of the  German Research Foundation/Deutsche Forschungsgemeinschaft  ( DI 1731/2-1 ). I. H. was supported by intramural funds of the  University of Kiel , the  German Research Foundation  ( HE5415/3-1 ) within the EuroEPINOMICS framework of the  European Science Foundation  and the  German Research Foundation  (DFG,  HE5415/5-1, HE5415/6-1 ).
C. F. is supported by a grant from the  National Institute of General Medical Sciences  ( GM54899 ). A. A. is supported by a grant from the  National Institute of General Medical Sciences  ( GM118647 ). The  Solve-RD  project has received funding from the  European Union 's  Horizon 2020 research and innovation programme  under grant agreement No  779257  (to V. T. and P. D. J. ).
All data generated or analysed during this study are included in this published article (and its supplementary information files). Human sequence (variant) data that support the findings of this study have been deposited in ClinVar and are accessible through the accession codes: ID:402133, ID:402134, SCV000808053, SCV000808054, SCV000808055, SCV000808056, SCV000808057, SCV000808058 and SCV000808059. All other relevant data are available from the corresponding authors on request.
First, additional investigations should be done to improve the formalism and hypotheses of microscopic diffusion (see e. g. Turcotte et al. 1998; Schlattl 2002; Gorshkov & Baturin 2008 , 2010). Comparisons between evolutionary codes from various groups (such as in  Lebreton et al. 2007; Montalbán et al. 2007 ) could be pushed at the level of accuracy of helioseismology and provide crucial insights by pinpointing the intrinsic differences between each model, regardless of their (dis)agreement with the Sun. Second, further analyses using higher degree modes such as those derived from recent MDI datasets  (Reiter et al. 2015)  could prove very useful to revisit studies such as those of Di  Mauro et al. (2002) ;  Lin & Däppen (2005) ;  Vorontsov et al. (2013)  to constrain the upper parts of the convective envelope, the equation of state and the abundance of heavy elements (see also  Vorontsov et al.
Acknowledgements AM and GB acknowledge support from the  ERC   Consolidator Grant funding scheme  (project  ASTEROCHRONOMETRY , G. A. n. 772293). We gratefully acknowledge the support of the  UK Science and Technology Facilities Council (STFC). S. J. A. J. S. is funded by the  Wallonia-Brussels Federation ARC  grant for Concerted Research Actions. The work of  V. K. Gryaznov ,  I. L. Iosilevskiy  and  A. N. Starostin  was supported by  RAS   Scientific Program I. 13  "Condensed matter and plasma under high energy density conditions". This article used an adapted version of InversionKit, a software developed within the HELAS and SPACEINN networks, funded by the  European Commissions's Sixth and Seventh Framework Programmes. PE and GM acknowledge support from the  Swiss National Science Foundation  through the grant  200020-172505.
e n 0, ( ) 0 on (14c) n n n 0 In Eqs (  13 ) and (  14 ), vector n is normal to the boundary ∪ ∪ Γ = Σ Σ Σ 0 1 2 lat where Σ lat is the lateral surface of the straws. The cell problems (  14 ) are computed numerically by means of the Finite Element Method using commercial software COMSOL Multiphysics ®. The computations are performed in 3-D on a single unit cell with periodicity conditions. Problems in Eq. (  14a ) and (14c) are solved with module Coefficient Form PDE in Mathematics while problem in Eq. (  14b ) is solved with module Creeping flow in Fluid Flow. The geometry has been meshed with Free Tetrahedral elements, sufficiently small to ensure accuracy. To account for the corrugation on the cell problems, similar cell problems are computed for the square array of infinite cylinders with corrugated lateral surface and values of the tests-fields hence obtained are substituted into Eq.
COSINUS will also give us the opportunity to investigate the impact of other harm reduction tools in France and their combined effect with DCR on reducing HIV-HCV risk practices. Furthermore, we will be better able to identify PWID needs. Methods and analysis Enrollment in this prospective multi-site cohort study started in June 2016. Overall, 680 PWID in four different cities (Bordeaux, Marseilles, Paris and Strasbourg) will be enrolled and followed up for 12 months through face-to-face structured interviews administered by trained staff to all eligible participants at baseline (M0), 3 month (M3), 6 month (M6) and 12 month (M12) follow-up visits. These interviews gather data on socio-demographic characteristics, past and current drug and alcohol consumption, drug-use related practices, access to care and social services, experience of violence (as victims), offences, other psychosocial issues and perception and needs about harm reduction interventions and services.
MEthods And AnAlysIs study design This prospective, multi-center cohort study, which started in June 2016, will enrol a total of 680 PWID by October 2017 in four different French cities with different geographical and health characteristics (Bordeaux, Marseilles, Paris and Strasbourg). The study design and data collection tools were partly inspired by an evaluation of the Vancouver Downtown Eastside DCR (Insite)  26  and the Vancouver Injection Drug User Study. 27 Individual follow-up will last 12 months. PWID in the DCR in Paris and Strasbourg constitute the 'treatment' group (hereafter 'DCR-exposed'), while PWID already enrolled in harm reduction programmes constitute the 'control' group (hereafter 'DCR-unexposed'). These four cities were chosen because they were all candidates for the opening of DCR when the law permitting experimentation with DCR passed (Public Health Law from January 2016).
Data collection consists of face-to-face interviews (each lasting approximately 20-35 min) administered by a trained interviewer at baseline, 3 months, 6 months and 12 months. Data collection is coordinated by the logistics department of methodology and management (CMG) of ORS PACA -INSERM-IRD UMR1252 (SESSTIM) in Marseilles, under the supervision of the cohort's four PIs (Marc Auriacombe for Bordeaux, Perrine Roux for Marseilles, Marie Jauffret-Roustide for Paris and Laurence Lalanne-Tongio for Strasbourg), and is managed by each site investigator. Participants are compensated for their time with €10 worth of service vouchers after each of the four interviews.
In addition, to study the impact of the combined effect of different services (DCR, education about safe injection, other HR services) on the main outcome, we will use mixed-model regression analysis by adjusting for these different structural factors and other covariates. A Cox model-based approach (or duration models) will be used to study the impact of DCR attendance (or other HR services) for a certain event at a certain time (transition from injection to another mode of use, access to care). To take into account bias due to missing data and loss to follow-up, we will perform sensitivity analyses using the Heckman model, which adjusts for this potential source of statistical bias. 44 Analyses will be performed using several statistical software packages (SPSS V. 12. 0, Intercooled Stata V.
dIsCussIon The COSINUS cohort study is the first in France designed to assess the impact of DCR on HIV-HCV risk practices. It is important to note that DCR in France are seen as an additional tool to existing NEP and OMT programmes, as well as the recently education programme for safer injecting practices. 25 o date, most of the data published on the effects of DCR are from the Vancouver INSITE research team,  45  whose work greatly contributed to the preliminary design of our cohort study. However, the French and Vancouver contexts are very different in terms of substances available on the black market, access to OMT, sharing practices, sero-prevalence of HIV and HCV, and harm reduction policy. In France, an estimated 180 000 drug users are currently on OMT,  46  corresponding to an estimated coverage of 80% in urban areas.
66 The COSINUS cohort study will not only study the impact of regularly attendance in DCR on HIV-HCV risk practices in PWID in France, but will also assess the combined effect of DCR together with other HR services (eg, education about safer injection, access to OMT, social activities) on these practices. Some limitations have to be acknowledged. First, all the data collected were self-reported. Although the use of self-reports may be subject to social desirability bias, studies have shown their reliability in drug-using populations. 67 68 To control any such bias, we used trained interviewers independent of the participating harm reduction facilities. In terms of the diversity of our sample, all the PWID were recruited through easily accessible harm reduction facilities that conduct outreach actions, and which constitute the main contact that the PWID population has with the healthcare system.
Acknowledgements Members of the COSINUS scientific committee:  Henri-Jean Aubin  and  Nerkassen Chau  ( INSERM U669 ),  Pr Jean-Marie Danion  ( INSERM U1114  and  University Hospital of Strasbourg ),  Maurice Dematteis  ( University Hospital of Grenoble ),  Laurent Karila  ( INSERM U1000 ) and  Thomas Kerr  ( British Columbia Centre for Excellence in HIV/AIDS ).
| Bioinformatics analysis The quality of each sequenced library was assessed using FastQC (Babraham Bioinformatics, The Babraham Institute). A custom R script was used to sort reads into individual samples according to the unique barcodes. We discarded sequences containing ambiguous bases and reads that did not feature a valid Pst1 restriction site. Reads were aligned to the D. magna genome (v2. 4; Daphnia Genomic Consortium, WFleaBase) using Novoalign v2. 07 (http://novocraft. com) tolerating on average one high-quality mismatch per 12 bases. Only loci aligning to unique genomic locations were considered in further analyses. The average coverage obtained per individual per RAD-locus was 115x (SD = 17. 9) for IXF1, 134x (SD = 28. 3) for RM1-30, 146x (SD = 16. 5) for RM1-02, and 136x (SD = 16.
| D ISCUSS I ON Ameiotic recombination resulting in LOH may have important consequences for the evolutionary potential of asexual lineages. In this study, we performed reduced representation genome sequencing using the RAD-sequencing protocol to address the occurrence of genome homogenization events within a single asexual generation of D. magna. This design allowed us to minimize possible selection against LOH and to exclude cryptic sexual events. We have as- tives where heterozygotes had appeared as homozygotes. More precisely, maternal heterozygosity was confirmed in loci that were scored as homozygous in the RAD-sequencing analysis of asexual daughters (Figure  2 ). This revealed that the LOH rate estimated from our RAD-sequencing data most probably reflects sequencing biases that were not detectable using the bioinformatics analysis alone.
Scaffold01005_615383 using whole-genome sequencing obtained similar estimates of the LOH rate with values between 2. 14 × 10 -5  (Keith et al. , 2015)  and 4. 82 × 10 -5 per site per generation  (Flynn et al. , 2017). Since we investigated a total of 310,932 heterozygous sites (the RAD-markers were heterozygous at 1. 8 sites on average), this would translate into 7-15 LOH events expected in our dataset. In addition, all previous estimates are potentially confounded by selection against LOH that might have occurred during mutation-accumulation lines, and hence, they may be considered minimum estimates. Nevertheless, we were unable to identify any true LOH events in our data, which suggests that LOH events were either absent or much less frequent than expected based on previous estimates. Our inability to detect LOH could indicate that there is variation between D.
Implications of all the available evidence This study provides novel evidence that activating PPARα by fibrates prevent cartilage degradation by modulating key mechanisms such as senescence and autophagy in chondrocytes and cartilage. Collectively, our data establish that fibrates could be translated into disease-modifying therapeutics for OA patients. 2336382), Prestwick Chemical Library (Prestwick Chemical, Illkirch, France), Fenofibrate (Sigma-Aldrich, MO, cat# F6020, https://www. drugbank. ca/drugs/DB01039), GW7647 (Sigma-Aldrich, St. Louis, MO, cat# G6793, https://pubchem. ncbi. nlm. nih. gov/compound/3392731), CP775146 (Sigma-Aldrich, cat# PZ0173, https://pubchem. ncbi. nlm. nih. gov/compound/10410059), Rapamycin (Calbiochem, Germany, cat# 5053210, https://www. drugbank. ca/drugs/DB00877), Navitoclax (ChemieTek, IN, USA, cat# CT-A263, https://www.
Samples consent statement The samples needed to carry out this study were obtained from the collection of samples for the investigation of Rheumatic Diseases of Dr. Francisco J. Blanco García, from Xerencia de Xestion Integrada de A Coruña (XXIAC) and Instituto de Investigación Biomédica de A Coruña (INIBIC). This collection was registered in the National Registry of Biobanks, with registration code: C. 0000424 and approved by the Ethics Committee of Galicia with registration code: 2013/107. The information and informed consent sheet was given to all participants in the research, whose biological samples and clinical data may be susceptible to be used in this study and are authorized by the Ethics Committee of Galicia, Law 14/2007, of the July 3, and Biomedical Research 1716/2011 of November 18.
Cells were incubated with C 12 FDG substrate reagent (30 μM) and Hoechst 33342 (2. 5 μl/ml) for 1 h at 37 °C and 5% CO 2. SA-β-Gal activity was stopped with phenylethyl β-d-thiogalactoside (PETG, 1 mM) for 5 min at room temperature (RT) and cells were fixed with PFA 4% for 10 min at RT. CQ (200 μM) was employed as a negative control for SA-β-Gal activity. For data acquisition, images were captured by using the Operetta® High Content Screening system. This system is an automated microscope, which allows automated image adquisition and analysis. Each well was divided in four stacks with a working distance of 0. 2 μm. The first height was 7. 6 μm and the last height was 8. 2 μm. We selected three channels for analysis: Brightfield, Hoechst and Fluorescein. The images were captured using a 20× objective, long WD.
Data analysis for chondrocyte senescence SA-β-Gal data from the screening assay was analysed by using Harmony® Image Analysis Software. We calculated the average intensity of cytoplasmic fluorescein and number of nuclei in test samples, as well as in positive and negative controls. Then, we determined a threshold to define the maximum of senescence. For this, we subtracted twice the standard deviation from the intensity of cytoplasmic fluorescein was substracted two values from the standard deviation (mean -2SD). We use the mean -2SD value to select compounds from the Prestwick chemical library. We determined Z'factor, coefficient of variation (CV) values and signal-to-background (s/b) ratio for each plate  [35]. Screening assay plate data was considered acceptable if Z´≥ 0. 5 (Supplementary Fig.
Autophagy screen pBABE-puro mCherry-EGFP-LC3B plasmid was obtained from Addgene. mCherry-EGFP-LC3 retrovirus was produced as described previously  [36]. HEK 293-T17 (ATCC®, cat# CRL-11268, RRID:CVCL_1926) cells were used to facilitate retroviral packaging. We employed FuGene Transfection Reagent, a nonliposomal mixture of lipids as a plasmid delivery method. After confirmation of transfection by microscopy, cells were sorted. Next, we selected the brightest clones by testing the expression of mCherry and GFP by flow cytometry. Finally, Operetta was used to evaluate the autophagic flux of selected clones by imaging. Stable clones were maintained in the presence of Puromycin (2. 5 μg/ml). A Multidrop Combi Reagent Dispenser was used for seeding cells into 384-well plates (8000 cells/well) in DMEM media supplemented with 10% FCS, 1% P/S and 2.
Data analysis of autophagic flux Screening data were analysed using Harmony software. We calculated mCherry/EGFP Relative Spot Intensity with Harmony Analysis software. We obtained the mean and standard deviation of the positive and negative controls. We determined Z'factor, CV values and s/b (signal-to-background) ratio for each plate  [35]. We use the (mean + 2SD) value to select compounds from the Prestwick chemical library. Screening assay plate data was considered acceptable if Z´≥ 0. 5 (Supplementary Fig. 2 ).
Analysis of knee osteoarthritis patients treated with fibrates from Osteoarthritis Initiative (OAI) Cohort For the present study, we used longitudinal data obtained from the multicenter, longitudinal, prospective observational study of knee OA, Osteoarthritis Initiative (OAI). The OAI data are publicly available at https://oai. nih. gov. Specific datasets used were: "MIF00", "MIF01", "MIF03", "MIF05" (release versions 0. 2. 2, 1. 2. 1, 3. 2. 1, and 5. 2. 1, respectively); "AllClinical00", "AllClinical01", "AllClinical03", "AllClinical05" (release versions 0. 2. 3, 1. 2. 2, 3. 2. 1, and 5. 2. 1, respectively); "Enrollees00 (release version 25)"; "Outcomes99" (release version 10). The detailed information about the OAI protocol can be found at the osteoarthritis initiative protocol for the cohort study, from http://dataarchive.
nimh. nih. gov/binaries/content/documents/ndacms/resources/ oai/oai-study protocol/oai-study-protocol/ndacms%3Aresource. The OAI cohort consists of a progression subcohort (patients with symptomatic tibiofemoral knee OA, n = 1390), an incidence subcohort (subjects with increased risk of OA, n = 3284) and a reference control subcohort (n = 122). In this analysis we used the longitudinal data from both the progression and incidence subcohorts. The main inclusion criteria were the following: age between 45 and 79 years for both subcohorts, symptomatic tibiofemoral knee OA for the progression subcohort, and the presence of established or putative risk factors for incident knee OA for the incidence subcohort. The OAI participants were recruited and enrolled between February 2004 and May 2006 at four recruitment centres in the United States.
There were fewer joint replacement surgeries in patients taking fibrates. These findings are in line with an open label study performed on patients with erosive hand OA where FN use for 12 weeks was associated with significant improvements in the Cochin hand functional disability scale  [61]. In another exploratory study carried out through the OAI database, neither reduced radiographic progression nor reduction in worsening of pain in participants taking fibrates were detected. The authors did not assess the effects of fibrates on disability and used a prevalent user design (i. e. included participants who used fibrates at baseline)  [62]  that may be associated with bias  [63]  and may account for the non-detection of fibrate effect on pain. It is difficult to interpret the dissociation of fibrate effects on disability and pain found in this analysis as pain and functional limitation in knee OA are closely related  [64].
Acknowledgements We thank the staff of the  Orthopedic Department of the Complejo Hospitalario Universitario A Coruña  for providing the cartilage samples. Furthermore, we thank  Tamara Hermida  and  Merissa Olmer  for technical assistance and  Richard Roberts  for editing the revised manuscript in British English. The OAI is a public-private partnership comprising five contracts ( N01-AR-2-2258 ;  N01-AR-2-2259 ;  N01-AR-2-2260 ;  N01-AR-2-2261 ;  N01-AR-2-2262 ) funded by the  National Institutes of Health , a branch of the  Department of Health and Human Services , and conducted by the  OAI Study Investigators. Private funding partners include  Merck Research Laboratories ,  Novartis Pharmaceuticals Corporation ,  GlaxoSmithKline  and  Pfizer, Inc. Private sector funding for the OAI is managed by the  Foundation for the National Institutes of Health.
The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~40% familial cases and ~7% sporadic cases in the European population. In most people, the repeat length is 2, but in people with ALS, hundreds to thousands of repeats may be observed. A small proportion of people have an intermediate expansion, of the order of 20 to 30 repeats in size, and it remains unknown whether intermediate expansions confer risk of ALS in the same way that massive expansions do. We investigated the association of this intermediate repeat with ALS by performing a meta-analysis of four previously published studies and a new British/Alzheimer's Disease Neuroimaging Initiative dataset of 1295 cases and 613 controls. The final dataset comprised 5071 cases and 3747 controls.
Second, the fixed-effect model used in the meta-analysis assumes that the genetic effects are the same across the combined investigations, and that all differences are due to chance  [18, 19]. While this assumption appears to be supported by the lack of heterogeneity across the involved studies (Q-test p-value = 0. 61), heterogeneity may be masked. Genetic effects may vary across different populations for various reasons, including both genuine differences and differential biases and errors across studies  [20, 21] , and the C9orf72 repeat expansion exemplifies this variation  [13, 15, 16, 22, 23]. Moreover, the Q-test and I-squared do not describe heterogeneity well when the number of studies is small  [24, 25]  and the datasets did not provide sufficient power to properly test the meta-analysis studies for heterogeneity.
Whole-genome sequencing samples Whole-genome sequencing (WGS) data were obtained from blood samples of 1908 individuals, comprising 1295 people with ALS (all apparently sporadic cases) and 613 unaffected controls from two groups: a UK set of 1295 ALS cases, 340 matched controls  [26] , and 273 controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) WGS dataset (http://adni. loni. usc. edu). The UK dataset was generated as part of Project MinE  [26, 27] , on the Illumina Hiseq X platform (150 bp paired-end reads) and the ADNI dataset on the Illumina 2000 platform (100 bp paired-end reads).
Genotyping We used ExpansionHunter  [28]  to size the C9orf72 GGGGCC repeat in the WGS data. ExpansionHunter has been previously validated for C9orf72 repeat sizing in 5787 WGS samples from Project MinE that were also genotyped using repeat-primed polymerase chain reaction (PCR) and fluorescence PCR. Using the repeat-primed PCR calls as the gold standard, ExpansionHunter showed an expansion detection accuracy > 99%  [28]. ExpansionHunter also showed high concordance with PCR and Sanger sequencing in repeats whose total length did not exceed the read-length  [28, 29] , while providing a confidence interval for longer repeats. We used the Expansion-Hunter repeat length called when repeat sizes had a read length < 25 repeats for the UK dataset and < 17 repeats for the ADNI dataset to account for the difference in sequencing platform, and we used the Fig.