dataesr/scientific-paragraphs-categorization huggingface dataset:
Administrative claims data Administrative claims data were provided by the regional reimbursement database (Extraction, Recherches, Analyses pour un Suivi Medico-Economique, ERASME). This database contains information on all reimbursement data for patients affiliated to the main French NHI living in the Rhône-Alpes area, including drugs and hospitalizations ordered by physicians, for the previous 24-month period. 15 e focused on ten therapeutic classes as follows (drug names are presented in Table  S1 ): drugs for obstructive airways disease (ie, beta-2-adrenoreceptor agonist or glucocorticoid aerosol), mucolytics (dornase alfa), inhaled anti-infectives (ie, colistin or tobramycin), oral anti-infectives (ie, azithromycin or itraconazole), CFTR potentiator (ivafactor), drugs for acid-related disorders, digestive enzymes (lipase and protease), bile acids, vitamins and mineral supplements (ie, calcium or tocopherol), and antidiabetics (insulin and oral hypoglycaemic drugs such as repaglinide).
Adherence measurement We derived a measure for adherence combining prescription data and administrative claims data. Administrative claims data provide an objective estimate of adherence for multiple medications, large samples, long follow-up periods, at low cost, and without intrusion. 18, 19 We calculated adherence using continuous medication availability (CMA) which evaluates both implementation (to take medication in accordance with the recommended dosing regimen) and persistence (to continue taking it for the recommended duration). 20 We used CMA version 7 to calculate adherence during the prescription period; this is defined as the proportion of days covered by a medication during the observation window (OW; ie, the period for which adherence is calculated), for each individual medication.
Statistical analyses Mean and SD or median and (range) for continuous variables and frequency and percentage for categorical variables were used to summarize demographic and clinical characteristics as well as the adherence rate. Chi-square tests were used to compare age and gender between patients included and those who were not included. We analyzed the data according to five age groups consistent with stages of illness and treatment of CF patients: 0-5 years, 6-11 years, 12-17 years, 18-25 years, and 26 or older. Correlations between age and number of medications were assessed by the Spearman's test. We compared cCMA for each therapeutic classes, PO_cCMA, Inhal_cCMA and overall cCMA by age group and pharmaceutical forms using the Kruskal-Wallis test. The significance level was set at 0.
Discussion The present study found that among adult and pediatric French CF patients, the mean cCMA was 0. 67 and for all age groups was above 0. 50. These results are consistent with data from the latest targeted literature review, although the study population and the therapeutic classes studied in this study are more extensive. 7 Despite French NHI allows a free providing of all drugs that have been covered in the study, adherence rates do not seem to be notably higher than in countries without this system. The financial barrier does not seem to be the main barrier to adherence. Figure  2  Mean cCMA and 95% confidence interval for all medication (overall cCMA), oral medication (PO_cCMA) and inhaled medication (Inhal_cCMA) according to age. Notes: We used the open-source package AdhereR to calculate cCMAs, and the Kruskal-Wallis test to compare PO_cCMA, Inhal_cCMA, and overall cCMA by age group and pharmaceutical forms.
] [37] [38] [39]  The study does, however, have some limitations which can result in over estimation of adherence levels. The first is patient recruitment as less than half of those invited to participate did so. The study may therefore have been affected by selection bias as those who did not consent to participate are possibly those with worse adherence to treatment, and therefore the adherence levels reported in this article should be regarded as conservative estimates. The second limitation is due to the use of an administrative database that may overestimate the real administration of the drug may be lower than medication availability. However, in CF populations such a bias may not be a concern as Modi et al have reported that adherence rates from claims data were better than those estimated by selfreport measure substantially inflated by reporting biases and recall problems.
Acknowledgments We thank  Neziha Bensalem ,  Laetitia Bouveret ,  Sophie Hommey ,  Stephanie Polazzi , and  Marie Perceval  for their technical advice and their contribution during the implementation of the study and data collection. We also thank the  Direction régionale du service médical Rhône-Alpes de la Caisse nationale d'Assurance maladie des travailleurs salariés (DRSM) , the regional directorate of the  French National Health Insurance  for access to administrative claims data of its regional reimbursement database (Extraction, Recherches,  Analyses pour un Suivi Medico-Economique, ERASME). This work was funded by the  association Vaincre la Mucoviscidose (VLM)  ( RC20150501406 ).
Flow chart for the study. Total patients taken care of in the four regional CF centres in 2015 n = 801 Non eligible patients: 2 dead in 2015 5 moved to another CF centre in 2015 67 transplanted Eligible patients invited to participate in the study 114 not living in Rhône-Alpes region* n = 613 Patients who consented to participate in the study n = 287 Excluded patients: 53 not covered by NHI 2 non CF patients (excluded by genetic test) Patients with complete refill and medical records 1 pulmonary transplanted n = 231 3 excluded patients without medication prescribed for more than three months Population included in the study n = 228 1 excluded patient without any dispensation for his/her medication prescribed for more than Patients included for CMA calculation three months during the FUW n = 227 Figure 1 Note: *No administrative claims data in "ERASME" database.
Acknowledgements We want to express our gratittude to  Dr. Daniel E. Francés  for his kind help and valuable suggestions. We thank  Wiener Lab  for the generous gift of ALT, AST and ALP detection kits. We thank  Camille Le Guilcher  for providing us mouse tissues and for technical help. This work was supported by research grant  PICT 2013 No. 1693  ( M. L. Alvarez)  from  Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT).
7-597. 6 Mb; W ¼ 2; P ¼ 0. 003). Our analyses thus indicate that changes in intronic and intergenic regions largely account for genome-size differences in molluscs. The repeat contents in the apple snail genomes were identified using three de novo predictors and by comparison with a database of known repeats (Supplementary Material online). The ampullariid genomes contain 20. 5-30. 8% repeat content, which is significantly less than most other molluscan genomes (24. 2-61. 1%; W ¼ 4; P ¼ 0. 024), although the owl limpet (Lottia gigantea, 24. 2%) and the Yesso scallop (Patinopecten yessoensis, 27. 8%) fall within the range observed for ampullariids (supplementary table S6, Supplementary Material online). Among the four apple snail genomes, the larger Lanistes and Marisa genomes have $55 Mb more repeats than the smaller Pomacea genomes.
Acknowledgments This study was supported by the  Research Grants Council of Hong Kong  ( 261312  to J. W. Q. ),  Hong Kong Baptist University  ( SDF15-1012-P04  to J. W. Q. ),  Scientific and Technical Innovation Council of Shenzhen and Department of Education of Guangdong Province  ( 827000012 ,  2017KTSCX161 ,  KQJSCX20170330110206042  to Y. Z. ), the  Howard Hughes Medical Institute  (to A. S. A. ), the  Stowers Institute for Medical Research  (to A. S. A. ), the  Fund for Scientific and Technological Research (FONCYT-Argentina , to A. C. V. ), the  Society for Developmental Biology (SDB Emerging Models  grant to A. A. ), the  American Association of Anatomists  (postdoctoral fellowship to A. A. ),  FWO Vlaanderen  ( 12N3915N  to B. V. B. ), the  French Agence Nationale de la Recherche  ( ANR-JCJC-EVOLINK  to B.
Material Commercial red apples (Gala), bananas (Cavendish) and persimmons (Ribera del Xùquer) were selected as the raw materials for this investigation. The samples of good and uniform quality (with near-spherical shape for apples and persimmons and near the same size for banana) were purchased at a local supermarket (Compiegne, France) and stored at 4 o C. All experimental data were collected within 10 days of the purchase of the samples. The skins (thin slices with lengths of 20 mm and widths of 10 mm) were removed from the bananas by hand and from the apples and persimmons with a razor blade. For preparation of the freezethawed products the samples were frozen at -20 o C for 12 hours and then thawed at room temperature (≈23 o C) for 12 hours. The moisture content was determined by drying at elevated temperature at 105 °C to a constant weight using MA 160 infrared moisture analyzer (Sartorius, Göttingen, Germany) and it was (on wet basis) 84%, 89% and 76% for apple, banana and persimmon fresh skins, respectively.
Cell wall disintegration index The cell wall disintegration was analyzed using the confocal laser scanning microscopy  Processing of the CLSM images and calculation cell damage degree were done using the wholly automatic procedure supported with Matlab (Version 2011a, the Mathworks Inc. , Mass, USA). Figure  3  shows the scheme applied for the processing and calculation of cell damage degree. The following 5 steps were applied: 1) Pre-processing. For presentation of the cell walls the RGB image was transformed into the blue image. To reduce possible noise, the median-filtering technique (a special case of filter called rank-statistic filter), which allowed the edges to be preserved while filtering out the peak noise, was used  [41]. 2) Segmentation. To remove background, the blue image was transformed into the gray level image and then to the binary image (called bi-level images, BW).
Acknowledgments This study has been carried out with financial support from the  French Aquitaine region  [Grant  2015-1R10205 ] and by the  Canadian Excellence Research Chair program  (CERC) in Photonics Innovations. This work has been done in the frame of "the Investments for the future"  Programme IdEx Bordeaux-LAPHIA  ( ANR-10-IDEX-03-02 ). The authors are also grateful to the  Natural Sciences and Engineering Research Council of Canada (NSERC) , the  Fonds de Recherche Québecois sur la Nature et les Technologies (FRQNT)  and the  Canadian Foundation for Innovation (CFI)  for their financial support.
Methods This is a post-hoc study from the European multicenter registry on Coronary Artery Bypass Grafting (E-CABG), which is a prospective observational, multicenter study including patients undergoing isolated CABG. The detailed study protocol for the E-CABG registry has been published previously  [6]. The study was approved by the local regional or Data were collected consecutively from 16 cardiac surgery centers in six European countries (Finland, France, Germany, Italy, Sweden, and United Kingdom). All adult patients with acute coronary syndrome who were preoperatively treated with fondaparinux or LMWH and underwent isolated primary CABG in one of the participating centers from January 2015 to May 2017 were eligible. Preoperative dose and type of LMWH were not recorded. Exclusion criteria were (1) patients with discontinuation of fondaparinux or LMWH >24 hours prior to surgery and (2) patients treated with both fondaparinux and LMWH within 24 hours prior to surgery.
RA sample RA CpFAH12 ; CpFAD2, Claviceps purpurea fatty acid desaturase; CpFAH12, Claviceps purpurea fatty acid hydroxylase; FA, Fatty acid; FAD, Fatty acid desaturase; FAH, Fatty acid hydroxylase; FAME, Fatty acid methyl ester; His-Box, Histidine-box; LA, Linoleic acid (C18:2 Δ 9cis,12cis ); MD(s), Membrane fatty acid desaturase(s); OA, Oleic acid (C18:1 Δ 9cis ); RA, Ricinoleic acid (C18:1 Δ 9cis OH 12 ); SCD1, Stearoyl-CoA desaturase; TFA, Total fatty acids; TM, Transmembrane; WT, Wild-type. responsible for these modifications belong to two evolutionary distinct families called desaturases  (Shanklin & Cahoon, 1998) : the soluble fatty acid desaturases (Pfam: PF03405) only found in the stroma of chloroplasts and the cytosol of bacteria, and the membrane fatty acid desaturases (MDs; Pfam: PF00487) that are widespread in all organisms.
| Bioinformatics studies PSI/TM-COFFEE  (Notredame, Higgins, & Heringa, 2000) , PSIPRED  (Buchan, Minneci, Nugent, Bryson, & Jones, 2013; Jones, 1999) , and Interpro  (Finn et al. , 2017)  were used to make secondary structure prediction (SSP), and Phyre2  (Kelley, Mezulis, Yates, Wass, & Sternberg, 2015)  and I-TASSER  (Yang et al. , 2015)  were used to make predictive models also with SSP. The T-COFFEE package was used to make alignments between the two SCD1, CpFAH12, and CpFAD2 to infer the localization of secondary structure. The alignment with the 10 MDs were made by PROMALS3D  (Pei, Kim, & Grishin, 2008).
| Homology modeling of CpFAH12 The CpFAH12 model was generated using the Rosetta software, which allowed us to combine threading and comparative approaches through RosettaCM protocol  (Song et al. , 2013). Regarding the threading approach, fragment libraries of three and nine amino residues were built using the Robetta server  (Kim et al. , 2004). To identify the best template for the comparative approach, we ran the sequence of CpFAH12 through HH server  (Söding et al. , 2005). This server uses hidden Markov motif to spot similarities within secondary structures even if sequences share a low percentage of identity. Despite sharing only 12% of identity with CpFAH12, the secondary structure of SDC1 from Mus musculus (pdb: 4YMK)  (Bai et al. , 2015)  was identified as the best template with its perfect coverage of the residues 105-399.
Since the chosen template had such a low percentage of identity, to build a likely CpFAH12 model, we had to implement some constraints: (a) Based on the predictions of both Octopus  (Viklund & Elofsson, 2008 ) and the TMHMM2. 0 software  (Möller, Croning, & Apweiler, 2001) , we put a constraint on the TM helices; (b) based on the structure of SCD1, we constrained the eight histidine residues (His155, His159, His191, His194, His195, His391, His394, and His395), which, thanks to sequence alignment, had been previously identified as part of the three histidine-box (His-Box) motifs, to keep intact ions coordination sites. All these constraints were added to the RosettaCM protocol and 250 models of the core domain (105-399 residues) were generated. All models were evaluated with ProQM  (Ray, Lindahl, & Wallner, 2010)  assessment program and the model with the best score and a good His/ion coordination was selected.
, with kanamycin resistance for Escherichia coli amplification and Ura3 selection marker for Yarrowia lipolytica expression. The gene was expressed under the strong constitutive promoter pTEF. Plasmids containing either the wild-type (WT) CpFAH12 or the WT CpFAD2 or a CpFAH12 chimera, and optimized for Y. lipolytica, were synthetic plasmids ordered either from GenScript (Piscataway) or Synbio Technologies (Monmouth Junction). The accession numbers of both CpFAH12 and CpFAD2 are listed in Table.
FADs to perform studies on the molecular determinant F I G U R E 5 Alignment with PROMALS3D of eight Δ12-FADs of Fungi (Claviceps purpurea, Yarrowia lipolytica, and Mortierella alpina) and Plantae (Arabidopsis thaliana, Physaria fendleri, and Ricinus communis) and of the two mammalian SCD1 with available tree-dimensional structures (accession numbers listed in TableS2). The helices are shown in cyan and TM helices are underlined. The italic cyan helix for CpFAH12 and CpFAD2 were obtained by secondary structure prediction whereas cyan helices for SCD1 were obtained directly from the structure. The red letters are the four amino acids that differs between the Cyt2' of CpFAH12 and CpFAD2. The position Ile198 in CpFAH12 and the equivalent position in other MDs have been put in bold character. The black boxes encompass the His-Boxes [Color figure can be viewed at wileyonlinelibrary.
Δ 12 - 12 FADs to perform studies on the molecular determinant F I G U R E 5 Alignment with PROMALS3D of eight Δ12-FADs of Fungi (Claviceps purpurea, Yarrowia lipolytica, and Mortierella alpina) and Plantae (Arabidopsis thaliana, Physaria fendleri, and Ricinus communis) and of the two mammalian SCD1 with available tree-dimensional structures (accession numbers listed in TableS2). The helices are shown in cyan and TM helices are underlined. The italic cyan helix for CpFAH12 and CpFAD2 were obtained by secondary structure prediction whereas cyan helices for SCD1 were obtained directly from the structure. The red letters are the four amino acids that differs between the Cyt2' of CpFAH12 and CpFAD2. The position Ile198 in CpFAH12 and the equivalent position in other MDs have been put in bold character.
Neuroimaging data acquisition All participants were scanned on the same magnetic resonance imaging (MRI) and positron emission tomography (PET) cameras at the Cyceron Center (Caen, France): a Philips Achieva 3. 0 T scanner and a Discovery RX VCT 64 PET-CT device (General Electric Healthcare), respectively. High-resolution T1-weighted anatomical volumes were acquired using a 3D fast-field echo sequence (3D-T1-FFE sagittal; repetition time = 20 ms; echo time = 4. 6 ms; flip angle = 10°; 180 slices with no gap; slice thickness = 1 mm; field of view = 256 × 256 mm 2 ; in-plane resolution = 1 × 1 mm 2 ). In the present study, we used the baseline and the follow-up MRI scans; the mean duration between serial MRI was 2. 4 years (± 0. 8 years). Follow-up MRI scan was missing in 1 HC, 1 SCDcommunity, and 3 SCD-clinic participants.
Neuroimaging pre-processing Cross-sectional data Neuroimaging pre-processing was performed using the Statistical Parametric Mapping version 12 (SPM12) software (Wellcome Trust Centre for Neuroimaging, London, UK). T1-weighted MRI were segmented using multimodal segmentation (T1-weighted MRI, T2-weighted MRI, and Flair) and spatially normalized to the Montreal Neurological Institute (MNI) space. Then, the normalized grey matter segments were modulated to correct for nonlinear warping effects, and the resultant images were smoothed using an 8-mm full-width half-maximum (FWHM) Gaussian kernel  [57, 67, 68]. PET data were corrected for partial volume effects using the Muller-Gartner method, coregistered onto their corresponding MRI, and normalized using the deformation parameters defined from the MRI procedure.
Statistical analysis Cross-sectional data To assess whether the control and both SCD groups differ in terms of demographic and clinical variables or self-reported global R SCD, variance analyses (ANOVAs) with one three-level (group) factor were performed. To highlight the differences between the three groups regarding the factors of interest potentially related to SCD or memory clinic consultation (i. e. psychoaffective measures, informant-reported SCD, types of SCD), we performed analyses of covariance (ANCOVAs) with one three-level (group) factor correcting for age and education, for all continuous variables-except for w-scores where ANOVAs were performed without covariates as age and education were already partialled out. Group differences for categorical variables were assessed using chi-square tests.
The cognitive substrates of self-reported SCD were assessed in each group using correlations, correcting for age and education for all variables but w-scores. Correlations were performed between self-reported global R SCD score and self-reported SCD factors, informant-reported global R SCD, cognitive performances (global cognition and memory w-scores), and psychoaffective measures (anxiety and depression). All statistical analyses of behavioural data were performed using the STATISTICA software (v13. 0, StatSoft Inc. , Tulsa, OK). The cerebral substrates were assessed in each group using regression analyses correcting for age and education between the self-reported global R SCD score and cross-sectional MRI and PET (FDG and Florbetapir) data. All statistical analyses of neuroimaging data were performed using the full factorial design in SPM12.
Longitudinal data To determine whether SCD, cognitive, and psychoaffective measures significantly changed over time, the individual slopes of regression line were compared to zero for each SCD group separately, using one-sample t tests. Then, to assess whether the changes in these measures significantly differed between the groups, the slopes of regression line were compared between the groups using ANCOVAs with one two-level (group) factor, correcting for age and education, for each SCD, cognitive, and psychoaffective measures. Thirdly, to assess whether the atrophy progression over time significantly differed between the groups, an ANCOVA with one three-level (group) factor with age and education as covariates was performed in SPM12. Finally, to improve our understanding of the predictors of cognitive decline, regression analyses were performed within each SCD group between baseline SCD scores or psychoaffective measures and the slope of cognitive decline, correcting for age and education, using general linear models and the STATISTICA software.
Acknowledgements The authors thank  F. Eustache ,  E. Arenaza-Urquijo ,  J. Gonneaud ,  R. De Flores ,  J. Mutlu ,  C. André ,  V. Ourry ,  F. Mézenge ,  M. Leblond ,  T. Anquetil ,  K. Mevel ,  N. Villain ,  M. Fouquet ,  A. Quillard ,  C. Schupp ,  J. Dayan ,  A. Chocat ,  JC. Baron ,  F. Viader ,  A. Pélerin ,  M. Gaubert ,  S. Egret ,  M. Delarue ,  G. Rauchs ,  A. Abbas ,  L. Barre ,  A. Manrique ,  D. Guilloteau , and the  Cyceron  staff members for their help with the data acquisition and the volunteers who were included in this study.
Then, the collagen was precipitated again with NaCl and washed with deionized water with intermediary centrifugations (6 times). Finally, the precipitated collagen was resuspended in 30 mL deionized water, frozen (12 h) and freeze-dried (48 h). The quantification of fluorochrome attached on chitosan and collagen was performed using a Varian Cary UV-Vis spectrophotometer 50 scan run by Cary Win UV version 3. 00 software. First, it was verified that neither unmodified chitosan nor unmodified collagen dissolved in AcOH exhibited significant absorption between 600 and 800 nm. To quantify Cy5. 5 in modified chitosan (Ch95), reference solutions were prepared by mixing the appropriate volume of Cy5. 5 mother solution (1 mg/mL in DMSO) with AcOH 0. 1 M aqueous solution to reach cytochrome concentrations ranging from 0 to 0.
3 mg/mL, AXIENCE) at 0. 05 mg/kg. A small incision of about 1 cm was performed on the left and the right side in the dorsal midline of the mice followed by a subcutaneous dissection below the panniculus carnosus to create a pocket on each side of the midline into which each implant was placed. The skin was closed by running sutures with Prolene 5/0 (at least 2 sutures) and the area was disinfected by application of an antiseptic solution. Post-surgery observations were performed during two days, including wound and animal behavior verifications. In order to follow the degradation of the samples by transdermal fluorescence imaging, the data acquisitions were performed on samples labelled by the fluorochromes Cy7 and/or Cy5. 5 using a Perkin Elmer IVIS Spectrum optical imaging system at different times post implantation, i.