dataesr/scientific-paragraphs-categorization huggingface dataset:
Author Manuscript This article is protected by copyright. All rights reserved The participating centres were categorized as having high, intermediate, and low rates of plasma transfusion according to the proportion of transfused patients in the observational study, i. e. > 75 th percentile, between the 25 th and 75 th percentile, and < the 25 th Differences were considered statistically significant when a two-sided α level was < 0. 05. No adjustments were made for multiple comparisons, as the different questions are not independent and as this would increase the risk of type II errors. All statistical analyses were performed with SPSS version 22 for Mac (SPSS, Chicago, IL, USA). percentile, respectively. Differences between the centres with high and low rates of plasma transfusion were evaluated using the Mann-Whitney test.
Acknowledgments We would like to thank all of the PlasmaTV investigators. PlasmaTV investigators:  Australia: Warwick Butt ,  Carmel Elope ,  Kym Bain  ( Royal Children's Hospital, Melbourne );  Simon Erickson ,  Nathan Smalley  ( Princess Margaret Hospital for Children, Perth ;  Tavey Dorofaeff ,  Debbie Long  ( Royal Children's Hospital, Brisbane );  Nathan Smalley ,  Greg Wiseman  ( Townsville Hospital, Townsville ). Belgium:  Stéphan Clément de Cléty ,  Caroline Berghe  ( Cliniques universitaires Saint-Luc, Brussels ) ;  Annick de Jaeger  ( Princess Elisabeth Children's University Hospital, Ghent ) ;  Pierre Demaret ,  Marc Trippaerts  ( CHC-CHR. Liège) ; Ariane Willems, ShancyRooze (Hôpital universitaire  des enfants  Reine Fabiola , Liverpool) ;  David Inwald ,  Amina Abdulla ,  Sophie Raghunanan  ( Imperial College Healthcare, London ) ;  Bob Taylor  ( Royal Belfast Hospital for Sick Children, Belfast ) ;  Alison Shefler ,  Hannah Sparkes  ( Oxford University Hospitals, Oxford ).
We also sought to determine whether these proliferation-enhancing effects were specific to the chelating function of DFX. For that, we have tested two other iron chelators routinely used in clinical practice, desferoxamine (DFO) and deferiprone (DFP). In order to determine the concentrations of DFO and DFP which trigger similar iron chelating effects as LD DFX, we measured the total iron concentration in leukemia K562 cells by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) (data not shown). We then transposed those concentrations in the erythroid differentiation model, and impaired cell proliferation after either DFO or DFP treatment was observed as compared to the control conditions (Figure  1B ), in contrast to the LD DFX effect. These expected results with DFO or DFP confirmed previously observed iron withdrawal effects on cell proliferation  [21].
The Malondialdehyde (MDA) level (p<0. 05) was slightly decreased with LD DFX, but no impact of DFX on carbonyls levels was observed (Figure  4B ). Neither SOD (SOD1-3) activity nor the GSH/GSSH ratio were significantly changed after LD DFX treatment (Figure  4B ). Remarkably, GPx activity was not detected in 6 different MDS samples in the iron overloaded system and, likewise, in 4 different MDS samples cultured in the more conventional, non-iron overloaded medium (data not shown). GPx4 and GPx8 were recently involved in redox homeostasis during erythroid differentiation  [23]. They were tested by RT-qPCR in seven different MDS samples cultured in iron-overloaded medium. GPx8 mRNA was only present in 1 sample, whereas GPx4 mRNA was present in all MDS samples without difference in relative expression in the presence of LD DFX (data not shown).
Western blots confirmed the presence of the GPx4 protein in samples of MDS patients treated or not with LD DFX and also in a healthy donor sample (Figure  4C ). We performed lysis of 3 MDS samples under nitrogen to avoid oxidative damage to the highly reactive active site selenocysteine of GPx4. As expected, GPx activity was detected, meaning that this activity was inhibited under oxygen-saturated conditions in the conventional lysis procedure. GPx activity was not modified by the LD DFX treatment (data not shown). These results outlined that the redox molecular shift associated with decreased oxidizing species induced by LD DFX was responsible for the lowered MDA values (Figure  4B ). Interestingly, lipid peroxidation is a hallmark of iron-dependent regulated necrosis, also termed as ferroptosis, which might be indicated by lowered MDA values.
These results provide a rationale for a French prospective clinical trial which will propose LD DFX (5 mg/kg/day) in MDS patients refractory to erythropoiesis stimulating agents (N° EudraCT: 2017-001258-33). To summarize, we have shown novel effects of LD deferasirox on NF-κB by fine modulation of ROS levels in low risk MDS erythroid progenitors. These results suggest that protection of MDS patients' bone marrow from oxidative stress should be considered early in the course of their disease, and before the development of a significant iron overload which requires high dose of DFX which does not result in erythroid improvement.
001% Tween-20 and then with deionized water removed the fluorescent reagent before chips were scanned on a Innoscan 1100 AL scanner (Innopsys, Carbonne, France) using an excitation wavelength of 543 nm at 10 µm resolution. Data on six spots per test compound on the chip surface were processed using ScanArray Express 4. 0 software and the fixed 70 µm-diameter circle method as well as Microsoft Excel, as described  [86, 87]. The results are reported as median RFU (relative fluorescence units) of replicates. Median deviation was measured as interquartile range. Any signal whose fluorescence intensity exceeded the background value by a factor of five (signals from ligand-free areas were counted as a background) was considered as significant.
Fluorescence plus Giemsa staining (FPG technique) Slides were exposed to a Hoechst 33258 (0. 05 mg/ml) solution for 10 min. Afterward, they were rinsed in distilled water, covered with 2 × SSC, and exposed to a 20 W ultraviolet lamp (>310 mm) for 60 min. Subsequently, the slides were washed in 2 × SSC, and then with distilled water. Finally, they were stained in a 4% Giemsa solution (in 2 × SSC) for 10 min, rinsed in distilled water, air-dreaded, and mounted. [34] Giemsa staining images were captured with the Metafer4 software (MetaSystems, Germany) on a Zeiss Axioplan microscope, and mitotic index and percentages of second metaphases were estimated for each experimental condition.
DEM simulation In order to better understand the wear process occurring within the Micro-Deval device, a discrete element simulation of the test  [4, 5] , using a Non-Smooth Contact Dynamics approach (NSCD)  [6] , has been performed and compared with the experimental results. The drum has been numerically built following the European code  [1, 2] : 40 cm long with a 20 cm inner diameter. The grains have been randomly chosen from a database of 1000 different modelled ballast grains. This database has been built following the correct ballast grain-size distribution using polyhedral shapes containing from 12 to 70 faces and from 8 to 37 vertices. In order to cover the required 10 kg of ballast, 109 grains are required with a density of 2700 kg/m 3. Collisions are considered perfectly inelastic and grains are modelled as rigid bodies.
As a perspective for further studies, the morphology description of a grain, especially concerning roughness and angularity, should be associated to a specific point in the wear rate curve. The authors gratefully acknowledge Denis Tunkin for his contribution to the study of shape evolution during his Master thesis. The Laboratoire 3SR is part of the LabEx Tec 21 (Investissements d'Avenir -grant agreement n° ANR-11-LABX-0030).
Experimental Setup In order to validate the proposed concept, the NMPC with deadzone-quadratic penalty function is experimentally implemented on the Smart-ED vehicle and the Ext-Eco-CC system is tested on the CFC test track. The position of the Smart-ED is updated by the Global Positioning System (GPS) sensor. The velocity and energy consumption of the vehicle including the battery current and voltage information is updated by the Controller Area Network (CAN-bus) through the On-Board Diagnose (OBD) interface. The onboard computational resource for the Ext-Eco-CC concept is foreseen by a Linux operating system on the Intel R Core TM i7 with a memory of 7. 7 GiB PC and connection panel. The connection panel is developed for the system power supply and actuators communication (Fig. 5 ). The control input of the proposed NMPC with deadzone-quadratic penalty function is realised by actuating either the accelerator pedal or brake actuator.
PCSK9 and LDL Receptor Assays. PCSK9 and LDLR were measured using the Proseek ® Multiplex CVDIII panel (Olink Proteomics AB, Uppsala, Sweden) according to the manufacturer's instructions. The Proximity Extension Assay (PEA) technology used for the Proseek ® Multiplex protocol has been well described  (16). In brief, pairs of oligonucleotide-labeled antibody probes bind to their targeted protein, and if the two probes are brought in close proximity the oligonucleotides will hybridize in a pair-wise manner. The addition of a DNA polymerase leads to a proximity-dependent DNA polymerization event, generating a unique PCR target sequence. The resulting DNA sequence is subsequently detected and quantified using a microfluidic real-time PCR instrument (Biomark HD, Fluidigm). Data is then quality controlled and normalized using an internal extension control and an inter-plate control, to adjust for intra-and inter-run variation.
Limitations: The current study had some limitations. First, the data presented here are valid for patients with worsening HF, mainly due to reduced LVEF. It remains to be determined whether soluble PCSK9 is also a good predictor for patients with stable chronic HF. Currently available data in the context of coronary artery disease showed in mice that plasma PCSK9 concentration was mostly elevated in the early hours after an acute coronary syndrome  (36). The second limitation was that the assay used to measure PCSK9 and LDLR was designed for research only, and its use cannot be recommended in clinical practice. Nevertheless, both exposures were measured with state-of-the art proteomics technology, currently available and well validated  (16). The last limitation was that genetic mutations that might determine PCSK9 levels were not measured in patients enrolled in the BIOSTAT-CHF trial.
This project was funded by a grant from the  European Commission  ( FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29 ). AB-G was supported by grants from the  Ministerio de Educación y Ciencia  ( SAF2014-59892 ),  Fundació La MARATÓ de TV3  ( 201502 ,  201516 ),  CIBER Cardiovascular  ( CB16/11/00403 ), and AdvanceCat 2014-2020. will result in better outcomes in HF.
METHODS A 16-year prospective study of IBD patients < 19 years of age was conducted in the Czech Republic (the Pilsen region). All incident IBD cases within a well-defined geographical area were retrieved from a prospectively collected computerized clinical database. Historical Czech data were used for comparison  (1990) (1991) (1992) (1993) (1994) (1995) (1996) (1997) (1998) (1999) (2000) (2001). Our catchment population was determined from the census data. We calculated the incidence by relating the number of newly diagnosed cases to the size of the.
Study population and data collection This clinical population-based prospective regional cohort consisted of children and adolescents with new onset IBD (< 19 years old at the time of diagnosis) whose residential addresses were in the Pilsen region. The study cohort included children from the same geographic region who were living in different settings (rural vs urban). Only unequivocal IBD cases were captured upon diagnosis over a 16-year period (between January 1, 2000 and December 31, 2015). The following demographic elements were available: age, sex, race/ethnicity, place of residence, and Czech census region. Patient data were entered consistently with the first diagnosis; thus, if subjects were diagnosed initially with IBD-U and subsequently reclassified to CD and UC, the former was considered the most accurate diagnosis.
Additionally, all pediatric departments within the area collaborated on the project. Detailed information from the diagnostic workup data for all subjects, including data from the first attendance and from the hospital discharge records, were prospectively collected from an in-house computerized clinical database (patient registries). The the resident pediatric populations under effective observation from January 1, 2000 to  December 31, 2015 (denominator). The data were analyzed for each time period and stratified by age, sex, and Czech census region. The IBD patients were analyzed in two separate categories with respect to age: < 10 years and 11-19 years. The age of the IBD patients was expected to have a skewed distribution because the median was used. Incidence trends and time projections of IBD and its subtypes with the number of cases as the dependent variable, and population size as the offset variable, were estimated using linear regression analyses and correlation coefficients.
Demographics and IBD incidence The demographic characteristics are shown in Table  1. As of 2015, the data from 170 incident patients (< 19 years), including 96 subjects (< 15 years of age at diagnosis) with pediatric-onset IBD in the Pilsen region (since 2000), were entered into the electronic databases. Of the entire group, 59. 4% were males. The median age in years was 14. 2 (range: 1. 4-18. 3) for IBD, 14. 1 (1. 4-18. 1) for CD, 14. 6 (2. 7-18. 3) for UC, and 14. 1 (2. 5-17. 7) for IBD-U. The median age at diagnosis did not differ between CD and UC, and there were no significant differences between the age at onset in boys and girls. The self-reported racial/ ethnic distributions were 97. 1% Caucasian and 2. 9% other. The number of cases diagnosed each year in the inclusion period is shown in Figure  2.
Of the new cases, 105 (61. 8%) were CD, 48 (28. 2%) were UC and 17 (10%) were IBD-U. There was a predominance of CD (the CD to UC ratio was 2. 2:1). Of the 17 subjects with IBD-U, the initial IBD-U diagnosis was changed in 13 (76. 5%), with 7 (41. 2%) reclassified to UC and 6 (35. 3%) reclassified to CD during the follow-up. During the 16-year study period, there were 1709209 person-year observations aged < 19 years in the catchment area, summarizing the source population data on patients were collected using a data form completed by gastroenterologists. The system has been developed in cooperation with the University of West Bohemia in Pilsen, Faculty of Applied Sciences. The application, which has a common client service architecture, provides the means to collect the data both manually via structured web forms and automatically from other medical systems using the Czech data standard for the exchange of medical data (DASTA).
Fully automatic data interchange between the application and hospital information system reduces the possibility of human error during data entry, thus improving the data accuracy and quality. All data from the work-ups were present in the central dataset, forming the data network with high quality, and complete detailed information was linked at a subject level. For this reason, there was presumably no bias in the sampling or selection procedure. The size of the pediatric population (< 19 years old) and ageand sex-stratified population data were determined from census data collected between 2000 and 2015.
In our population, there were important changes in higher socio-economic status and in demographic or environmental health conditions over time, which may have altered the frequency of disease. However, even in low-incidence countries, the occurrence of IBD seems to be rising. Thus, increased awareness by physicians and advancements in the diagnosis of IBD, homogeneity of registration databases, data collection methods, and possibly the completeness of case ascertainment may partially contribute to the striking increase in the incidence of IBD and geographic differences. We consider this a very plausible explanation for the precipitation of the clinical illness, although there are no clear answers from this research in terms of the relevance of the explanation in the Czech Republic. More detailed studies are warranted.
The Czech Republic is a country with centralized health care for IBD, and pediatric IBD subjects are cared for only in our tertiary hospital in the catchment area. Therefore, we trust that the sample is representative due to the easily surveyable area of the Pilsen region. Due to the centralization of pediatric gastroenterology care, we believe that all pediatric patients residing in the Pilsen region were included in the database, reducing the probability of recall bias. Thus, it is highly probable that all children with IBD in the Pilsen region sought medical attention in our clinical setting. In the assessment of time trends, we reported 16 years of data with figures specifying the numeric incidence rates over a long time period. This study was also strengthened by reliable data from the files and our registry of pediatric IBD in the included area.
This study revealed a marked increase in the incidence of CD over the 16-year period, such that CD is now much more common than UC and IBD-U in children in the Pilsen region and exhibits a persistent male preponderance. The reasons for these trends are unknown, and further studies in different regions of the country would be helpful to determine whether these trends are present in other areas of the Czech Republic. Further database projects may be attempted with software data, which should permit future research due to greater region specificity. As the changes in the past decades in industrialized countries cannot be interpreted by changes in genetic background, the influence of environmental hazards on incidence appears to be a crucial area of study. This study reaffirms the need for analyses of time trends and subsequent research to better understand the combination of genetic/family history and environmental influences, to unravel concurrent factors in the etiology of IBD and to determine causal relationships in pediatric disease.
The resulting libraries were quantified by qPCR and sequenced using a MiSeq 2x300 paired-end run, as described by Illumina. Sequence processing Amplicon sequences were analyzed with the mothur software version 1. 36. 1  (Schloss et al. , 2009). Reads were processed largely following the Schloss standard operating procedure for MiSeq Illumina data  (Kozich et al. , 2013). First, contigs between read pairs were assembled, resulting in 10 780 918 raw paired-end DNA sequences. Then, barcode and primer sequences and low-quality sequences were removed (minimum length of 350 bp, maximum length of 460 bp, removing any sequences with ambiguous bases and removing any sequences with homopolymers longer than 8 bp). Subsequently, sequences were aligned to the SILVA reference database release 119  (Quast et al.
, 2013)  and preclustered (pre. cluster, diffs = 1). Singletons were excluded (2 399 533 singletons, corresponding to 34. 91% of the sequences in this step), and chimeras were removed with the chimera. uchime mothur command (217 551 chimeric sequences, corresponding to 4. 86% of the sequences in this step). Then, sequences were classified using the k-nearest neighbor (knn) algorithm implemented in mothur and the BLASTN search method with the SILVA reference database release 119  (Quast et al. , 2013). Classification with the knn algorithm was chosen because this method was more accurate than the more commonly used naïve Bayesian classification method  (Wang et al. , 2007)  for our data. After classification, noneukaryotic, unknown and unclassified sequences were excluded (that is, 1 033 123 sequences).
To account for differences in sampling efforts, 5638 sequences were then randomly subsampled from each sample. Operational taxonomic units (OTUs) were generated using the average neighbor algorithm. An OTU was defined at the 99% sequence similarity level. After subsampling, the data set corresponded to 586 352 sequences with an average length of 398 bp. These sequences were clustered into 6900 OTUs. Finally, sequences were classified using the knn algorithm implemented in mothur and the BLASTN search method with the PR2 database (cut-off of 80%)  (Guillou et al. , 2013). The raw sequence data have been deposited in the NCBI Sequence Read Archive under the BioProject: PRJNA316490.
Diversity and statistical analysis Rarefaction curves (calculated from 10 000 iterations; Supplementary Figure  1 ), diversity indices, Venn diagrams and relative abundances of OTUs were computed with mothur  (Schloss et al. , 2009). All statistical analyses were computed using R software version 3. 2. 2 (https://www. r-project. org/). After normalization by random subsampling (5638 sequences in each sample, corresponding to the lowest number of sequences in a sample), the OTU matrix was log(1 +x) transformed, and a Bray-Curtis dissimilarity matrix was computed using the vegan package  (Oksanen et al. , 2015). Global non-metric multidimensional scaling (GNMDS) was computed using the same package based on the Bray-Curtis distances. The genetic diversity between the different locations was evaluated using analysis of molecular variance (AMOVA) and homogeneity of molecular variance (HOMOVA), which were both based on 1000 iterations and computed with mothur.
05) with respect to the class of interest (here NPS and GM); biological significance is subsequently investigated using a set of pairwise tests among subclasses using the (unpaired) Wilcoxon rank-sum test (Po0. 05). Finally, the algorithm uses LDA to estimate the effect size of each differentially abundant feature. In the present study, only OTUs presenting an LDA score4log 10 (3) and a significant threshold of Po0. 05 were considered as biomarkers of a class, that is, a compartment. To evaluate the co-occurrence probability between all OTUs, the Veech probabilistic model of species cooccurrence  (Veech, 2013)  was applied using the cooccur package  (Griffith et al. , 2016)  in R version 3. 2. 2. Negative and positive co-occurrences (Po0. 05) were then analyzed according to the taxonomic classifications of the OTUs.
Environmental DNA extracted from 104 samples (Supplementary Table  1 ) was purified and used for PCR amplifications. MiSeq sequencing generated 10 780 918 raw paired-end sequences. After quality filtering and chimera and singleton removal, we finally obtained a total of 6900 operational taxonomic units (OTUs; cut-off 99%) that were taxonomically assigned using the PR2 reference database. The abundance of all OTUs and richness values were calculated for each sampled site (Figure  2 ). Because the spring period corresponds to the maximum density of diatoms in the Seine River system  (Garnier et al. , 1995; Ducharne et al. , 2007; Flipo et al. , 2007) , and part as the consequence of using diatom-specific primers for library construction (see Materials and methods), OTUs assigned to diatoms corresponded to the most abundant fraction in all three compartments (FW, RW and GM), with an average of 61.
, 2014; Simon et al. , 2015). Another OTU presented a high similarity to the sequence of Pythium (Oomycetes, Stramenopiles) genera, known to be putative parasite of plants and animals  (Jiang and Tyler, 2012). Intriguingly, among the non-potable sources specific sequences, we also found invertebrate-related sequences. In particular, one OTU could be assigned to the freshwater sponge genus Ephydatia (Spongillina, Demosponges), and probably to Ephydatia fluviatilis (best BLAST hits with the GenBank nr/nt database). Ephydatia, in particular E. fluviatilis, is a relatively common and widely distributed species in rivers and lakes, where it can be found attached to growing mussels, rocks or bridges. The presence of Ephydatia in the water used for street sanitation is likely to correspond to the gemmule forms, which are resistant spore-like structures that develop in winter and then later develop into new sponge tissues  (Loomis, 2010).