dataesr/scientific-paragraphs-categorization huggingface dataset:
31  Additional data were provided by the application of TOF-SIMS for spatial localization of compounds of interest. The results correlated well with other analytical techniques. In this study, the distribution of lipid components in epidermis and dermis in the human skin was analyzed ex vivo after the application of individual FAs. The goal was to gain a better understanding of possible mechanisms of penetration enhancement and the effects of FAs on barrier characteristics of the skin. Straight-chain saturated fatty acids (SFA) (palmitic and stearic acids), monounsaturated fatty acids (MUFA) (oleic and palmitoleic acids), and a polyunsaturated fatty acid (PUFA) (linoleic acid) were selected for penetration studies into human skin ex vivo. Selected SFA, MUFA, and PUFA differ by their structure, presence in the skin, and application in pharmaceuticals and cosmetics compounding.
diameter polished silicon wafers, ACM, Villiers-Saint-Fr ed eric, France). The samples were dried under vacuum at a pressure of a few hectopascals for 15 min before the TOF-SIMS analysis. A subsequent skin section of each sample was cut and deposited on a glass slide to measure the thickness of the epidermis. A standard method of hematoxylin and eosin (H&E) staining was performed. Optical and H&E images were recorded with an Olympus BX51 microscope (Olympus, Rungis, France) equipped with lenses Â1. 25 to Â50 and a motorized scanning stage (Marzhauser Wetzlar GmbH, Wetzlar, Germany) and a SC30 color camera, monitored by OLYMPUS STREAM MOTION 1. 9 software. OLYMPUS STREAM MOTION software was used to measure the thickness of the epidermis in images of H&E stained samples. The thickness of the epidermis was measured at five points for each sample.
E. Data analysis The data were acquired and processed using SURFACELAB version 6. 2 (ION-TOF GmbH, M€ unster, Germany) software. Further analysis and manipulation of acquired data was carried out using ORIGIN Version 9. 0 (OriginLab, Northampton, MA) software. To determine the statistical significance of the intensity changes in the skin, a nonparametric Mann-Whitney test was applied using IBM SPSS Statistics for WINDOWS, Version 20. 0 (IBM Corporation, Armonk, NY). The level of significance was determined as p < 0. 05.
Proteinuria was divided according to the median value in our sample to take into account the supersaturation phenomenon that occurs in urine. Characteristics between recovery and nonrecovery groups were compared using Mann-Whitney test for continuous data and Fisher's exact test for categorical data. All tests were two-sided, and P < 0. 05 were considered statistically significant. Analyses were done using the Statview 5. 0 software package (SAS Institute, Cary, NC, USA).
The inhibitory effect seems more pronounced by combining both the use of extended pentapeptides and the introduction of fluorine atoms. This positive effect of the trifluoromethylation can be due to the increased polarity of the hydroxy group in the CF 3 -Thr residue, acting as a β-sheet breaker element and thus preventing the interactions between Aβ species  [15]. The introduction of such fluorinated peptides in larger structures, such as glycopeptide or β-hairpin compounds can be envisaged. Indeed we have previously demonstrated that small peptides/peptidomimetics that displayed inhibitory activity at high ratios show greater aggregation inhibitory activity at 1:1 ratio or even less, when they are incorporated in such designed structures  [15, [39] [40] [41]. member of the Laboratory of Excellence LERMIT supported by a Grant from ANR (ANR-10-LABX-33).
Nucleotide sequence accession number The 16S rRNA gene sequences were deposited in GenBank under the following accession numbers: 'Beduinibacterium massiliense' strain Marseille-P3337 T (LT631514), 'Massilimaliae massiliensis' stain Marseille-P2963 T (LT576408), 'Provencibacterium massiliense' stain Marseille-P2780 T (LT558850) and 'Oscilibacter massiliensis' stain Marseille-P2778 T (LT558848).
Finally, it has been proposed that the data should be made public no more than 6 months after publication of the original study in the journal. (9, 10, 14)  Clinicaltrials. com, a widely used non-for profit scientific repository,  (9, 10)  has already adapted its registration platform to specifically clarify data-sharing plans at the time of clinical trial registration. Obviously, this editorial initiative may have profound consequences on the planning, conducting and reporting of clinical trials and, in fact, may deeply influence research and publication strategies. (14)  As a result, the idea is to implement this requirement for any clinical trial that begins to enroll patients 1 year after the official adoption of this editorial policy by the corresponding journal. (14)  The initiative will also have major implications for the editorial process.
Indeed, Editors are supposed to monitor the data sharing process and, eventually, address potential irregularities. These might include requests of clarification to the authors, notification to academic institutions, publication of expressions of concern or even retractions. Finally, the ICJME acknowledges that the rights of the investigators and sponsors should be protected. (14)  Moreover, credit to the original report should be granted by including a unique identifier of the data set. It is emphasised that credit should always be given to the original investigators who posted the data after publication of their research. Furthermore, additional investigators using these databases should request collaboration of the investigators which originally collected the data to ensure adequate data interpretation, management and analysis.
(14)  This would require technical support and adequate funding. Data-access to non-trial researchers may disclose problems not recognised by the initial investigators. Although this will increase transparency and, therefore, trust in trial results, it might also generate confusion and undue scientific controversies. It is difficult to envision how the new researchers will gain the required detailed knowledge of the complicated datasets enjoyed by the original trial investigators. (14)  A reliable assessment of the data requires a deep knowledge regarding the study background and an ability to properly address the many nuances and practical considerations. These include precise information on the way variables were defined, how data was collected and how results were finally coded and entered into the database.
The initiative might be fraught with problems related to incorrect analysis resulting in inaccurate results and erroneous interpretations, potentially damaging science. (14)  Finally, Editors, already deluged with work, will need to check that all raw data contained in the published articles is eventually released, as promised. Different results may emerge from misconceptions regarding what data should be analysed to answer specific questions. (14)  If there are differences in results, it will be difficult to decide which analysis provides the most accurate reflection of the data. This could generate undue "scientific noise", with contradictory results and rectifications, which may generate confusion and frustration in the scientific community. Finally, this may also promote the simultaneous publication in several journals of conflicting results from the same database by different groups.
(18)  Some journals, such as JAMA, previously developed some related editorial initiatives, including the request for independent statistical analyses by an academic statistician of industry-sponsored trials. (19)  The World Health Organisation (WHO) and the Institute of Medicine (IOM) previously made important declarations on clinical trial transparency. In this regard, the IOM issued specific guidelines for trial data sharing. (20)  The WHO initially presented a statement on public disclosure of clinical trial results and, subsequently, encouraged sharing of research datasets whenever appropriate. (21) (22) (23)  More recently, the WHO developed global norms for sharing data and results during public health emergencies, with special focus on clinical, epidemiologic and genetic features of new infectious diseases and experimental therapeutics and vaccines.
(19)  Statistical guidance may be required for appropriate interpretation of results from re-analyses where different methods have been utilised. In particular, it is important to keep in mind the inherent risk of over-interpretation of the results from multiple subgroup analyses. (33)  Likewise, documents for best practices in data anonymisation have been developed. (34)  Statisticians should also be familiar with this methodology. Risk to patient privacy can be mitigated by data reduction techniques. Data holders are responsible for generating de-identified datasets to protect patient privacy through masking, or generalisation, of main identifiers. In addition, legally binding data sharing agreements should include a compromise not to attempt to identify patients. (34)  In particular, it is recommended that data use agreements are signed by the data holder and researchers.
CREDIT TO THE ORIGINAL AUTHORS A clear motivation for researchers to conduct randomised clinical trials is the opportunity to publish different studies in addition to the main manuscript with the primary endpoint. These secondary analyses may be of major value to unravel new findings from the original dataset. (35, 36)  Many have proposed that the time period to open the process of data sharing should be extended to 2 years, or even to 5 years in selected complex or large studies. This will allow precious time for original investigators to further scrutinise and analyse in depth their own data. As blinding is necessary during trial execution, once the study is completed the research teams concentrate on publishing the primary findings as soon as possible. Following this, there is usually a series of pre-planned additional analyses.
CONCLUSIONS The data transparency revolution is here to stay. This is just another step ahead towards a culture of "open science" and it is clear that we are at the dawn of a new age. (37, 38)  Several European National Societies have already developed registry programmes in which the registries databases are made public for use by their members. (39)  Major challenges and hurdles in the adoption and implementation of the new ICMJE recommendation must still be overcome. (40)  Experience gained by leading journals will eventually allow for a balanced compromise between the interests of the original researchers and that of the scientific community as a whole. NSCJ should progressively adapt their policies to increase awareness of the importance of data sharing and promote policies designed to enhance transparency in biomedical research.
Over 95% of patients were afebrile at Day 3 and complete parasite clearance was achieved at Day 3 in >99% of patients. Nineteen adverse events in nineteen patients were considered as possibly related to treatment, principally vomiting, abnormal liver function tests, and pruritus. There was no evidence for loss of effectiveness over the three-year period in spite of strong drug pressure. This trial was registered in the US Clinical Trials Registry (clinical. trials. gov) under the identifier number NCT01023399.
Data Collection. At the baseline visit, demographic features (age, gender, and weight), past medical history, concomitant medication, and clinical features presented were documented, and a fingerprick blood sample taken for smear tests using a vaccinostyle. At each follow-up visit, a physical examination was performed, clinical signs and symptoms documented, and a fingerprick blood sample taken. Blood samples were taken at Visits D7 and D28 (and at D14 in case of abnormal values on D7) for liver and renal function tests and blood cell count.
Several studies have reported that Lyn, but not Fyn, controls IgG-mediated or IgE-mediated systemic anaphylaxis  43, 44. Our data elucidate the role of these SFKs in the development of autoimmune and proinflammatory disease. Indeed, Fyn and Lyn deletion had opposing effects on the regulation of inflammation observed in R131H-FcγRIIA Tg mice. In the mild model of NTN, ablation of Fyn had no effect on young mice, but that of Lyn induced lethal nephritis associated with the activation of Syk and in situ phosphorylation of SHP-1 on S591. It is unlikely that SHIP-1 plays a negative role in this model through a putative engagement of FcγRIIB on infiltrating macrophages by mouse anti-rabbit Ig antibodies anti-GBM, as no phosphorylation of SHIP-1 was observed in situ. In addition, FcγRIIB function is Lyn dependent  45  and our results show that Lyn-deficient mice did not develop any severe nephritis as compared to WT mice after NTN induction.
Methods Humans. Eighteen individuals (8 healthy individuals and 10 patients with SLE) were studied. The SLE group was composed of 10 patients attending or referred to the Bichat's Hospital specialist nephrology unit between July 2014 and January 2016 meeting at least four ACR SLE criteria  47  presenting with active disease with nephritis proven by kidney biopsy (5 at class IV and 5 at class V) and in whom peripheral blood by venepuncture was obtained immediately prior to immunosuppressive therapy administration. All patients were female with age varying between 25 and 42. Ethical approval for this study was obtained from the Bichat Hospital Local Research Ethics Committee and informed consent was obtained from all patients enrolled. Data collection and analyses were performed anonymously.
Primers were purchased from Eurofins. Gene quantification was performed using a Chrom o4 Real-Time PCR Detection System (Bio-Rad Laboratories). Data were normalized to β-actin values. For primers and probe sequences see Supplementary Table  1. siRNA transfections. Experiments were performed using predesigned HP GenomeWide (Qiagen, Courtaboeuf, France) siRNAs. For targets DNA sequences and siRNAs sense and anti-sense see Supplementary Table  2. Single-strand sense and antisense RNA nucleotides were annealed to generate an RNA duplex according to the manufacturer's instructions. Cell lines were incubated with 5-10 nM of each siRNA tested and 2 µl of Lipofectamine RNAiMAX prepared according to the manufacturer's instructions (Invitrogen, Saint Aubin, France) for 48 or 72 h at 37 °C before use.
Slides were mounted with the Eukitt mounting medium (Electron Microscopy Sciences) and read with an upright microscope (DM2000; Leica) using the IM50 software (Leica). For colocalization experiments, frozen kidney sections were incubated overnight successively with each antibody (anti-phospho Syk Y525-526 AF488 (Cell Signalling) and anti-phalloidin AF568 (Life Technologies) followed by incubation with streptavidin-Alexa Fluor 488 (Life Technologies) at room temperature. Tissue sections were mounted with Vectashield (Vector Laboratories). Slides were read with a laser-scanning confocal microscope (LSM 510; Carl Zeiss) using a 63× objective and the LSM Image Browser (Carl Zeiss). For formalin-fixed hind paws and mouse knees, the samples were decalcified and embedded in paraffin. Sagittal sections were stained with haematoxylin and eosin.
Histological score of peri-articular exudates, synovitis and tissue loss were graded as 0 (normal), 3 (mild), 6 (moderate), or 9 (severe). The cumulative score of all features was used as histological score to represent overall disease severity. Analyses were made in a blind manner. Sections were incubated with rabbit primary antibodies against mouse phospho (p)-Syk (Y525-526)  49  , mouse p-SHP1 (S591) (both from Abcam), or p-SHP1 (Y536) (Assay Biotech). The presence of antibodies was detected with biotinylated anti-rabbit antibody (Southern Biotech) followed by peroxidase streptavidin and diaminobenzidine successive stains. Positive cells were quantified in hind paw sections with analysis software CaloPix (TRIBVN, Chatillon, France) after scanning with Aperio ScanScope CS (Leica Biosystems, Nanterre, France).
For immunofluorescence studies, frozen kidney slides or cytospined cells were incubated in blocking buffer (PBS, 0. 3% saponine, 1% BSA) for 30 min, and then with anti-phospho SHP-1 Y536 AF488, SHP-1 S591 AF647 (Bioss Antibodies, 1/50 dilution), anti-CD68 AF405 (Life Technologies 1/50 dilution), and anti-Phaloidin AF568 (Life Technologies,1/100 dilution) for 2 h. Fluorescence was detected by confocal laser scanning microscopy (CLSM-510-META, Zeiss). Statistical analysis. All data were expressed as mean ± SEM. Statistical significance between two groups was examined by the Student's t-test or the Mann-Whitney test, while the one-way and two-way analysis of variance (ANOVA) with Bonferroni's, Holm-Sidak's, or Newman-Keuls multiple comparisons test were used to evaluate multiple groups. Sample sizes were higher than five per group.
Acknowledgements This work was supported by grants from  ANR  ( MIEN-2009 and BLANC International-2012 ) and from  LabEx Inflamex  ( ANR-11-IDEX-0005-02 ). S. B. M. was supported by a grant from the  French Foundation ARC  ( PDF20100601037 ). R. C. M. is supported by ≪  Equipe ≫ program  of the Fondation pour la recherche médicale (FRM). We thank  Marieke Heineke  and  Loredana Saveanu  critical reading of this manuscript, and  Julie Bex  and  Erwan Boedec  for animal care. We are indebted to the patients and healthy volunteers who participated in the study.
Study population and statistical analysis We analysed all consecutive patients admitted with acetaminophen related ALF between 1990 and 2015 to the Intensive care unit of Royal Free Hospital (RFH), London (United Kingdom) and to the Liver Intensive Care Unit of Beaujon Hospital (BJH), Clichy (France). ALF was defined as the presence of severe liver injury with onset of hepatic encephalopathy (HE) within 12 weeks of the first symptoms  [11]. Patients with pre-existing liver disease were excluded. Clinical and laboratory data were collected at the time of admission as well as the use of mechanical ventilation support, vasopressors and continuous renal replacement therapy. The study endpoint was all-cause mortality during the first 3 months after the admission. Patients were listed for liver transplantation according to KCH criteria  [4]  (the modified version including lactate levels was applied from 2002)  [5].
Data for this study was obtained through archived patient notes in the hospital and the follow up data retrieved through a combination of follow up clinic notes, patient's general physicians and direct telephone contact with patients themselves. This database is updated at regular intervals and has been analysed for other purposes previously. The research and development department at the Royal Free Hospital where this project was undertaken, have defined the study as a clinical audit and service evaluation project with no requirement for formal ethics approval. The data was fully anonymised and the need for consent was waived by the R&D department. Continuous parametric variables were expressed as mean ± standard deviation and were compared using Student t-test. Non-parametric variables were showed as median and range, and compared with Kruskal-Wallis Test.
Molecular modelling studies Molecular mechanics simulation was done using the Macromodel-MMFFs force field in the presence of water (GB/SA implicit model) as implemented in the Schrodinger software (release 2014). The CD hosts were based on a non-distorted monomeric β-CD with C7 symmetry. trans-Ner were constructed manually. Fifty conformations of trans-Ner/CD complexes were selected (Monte Carlo conformational searches: Mixed torsional/low mode sampling, 10000 structures generated, FMNR conjugate gradient minimization, convergence fixed to 0. 01 kJ Å - 1  mol -1 ). The total energy difference (ΔE, kJ/mol) between the inclusion complex and the sum of their individual components in their optimized fundamental states was calculated (ΔE = E CD/Ner -(E CD + E Ner )) and used as the theoretical parameter to evaluate the complexation energy of the inclusion complex.
cDNA arrays Gene analysis derives from previous reports (Gene Filter, Research Genetics Inc. , Huntsville, AL, U. S. A. ). 18, 19 Transcription changes were analyzed using Ingenuity Pathway Analysis (QIAGEN, Redwood City, CA, U. S. A. ). Identification numbers from GenBank and its subset UniGene (both from the National Center for Biotechnology Information, Bethesda, MD, U. S. A. ) were used. Among the genes screened, we extracted the mRNA levels of NRs involved in drug metabolism. Protein isolation, subcellular fractionation, and Western blotting EPI-ECs used for the present study were passaged no more than two times after isolation. 11, 12 Total proteins were extracted from EPI-ECs, HBMECs, and hepatocytes as described previously. 11, 14 Subcellular fractions (cytoplasmic and nuclear) from EPI-ECs and HBMECs were fractionated using a Subcellular Protein Fractionation Kit (Pierce Biotechnology, Thermo Scientific, Rockford, IL, U.
Acknowledgments This work was supported by  National Institutes of Health  grants  R01NS078307  (to NM, DJ, and CG);  R42MH093302  and  R21HD057256  (to DJ); and  UH4TR000491  (to DJ and CG). Grants were awarded from  Brain and Behavior Research Foundation  (formerly NARSAD); the  American Heart Association  ( 13SDG13950015 ); and  Alternatives Research & Development Foundation  (to CG). We would like to thank  Dr. Jean-Marc Pascussi  who critically assisted us during the performance of this work.
Introduction Identification of strategies for detecting and preventing adverse reactions due to drugs and medication errors is one of the WHO global priority areas for patient safety research  [1]. An adverse drug reaction (ADR) represents ''a response to a medicinal product which is noxious and unintended, that arises from the use of the product within or outside the terms of the marketing authorization'' (including off-label use, overdose, misuse, abuse and medication errors) or from occupational exposure, as defined by the European Medicines Agency  [2, 3]. In low-and middle-income countries (L/MICs), there is relatively little drug safety research, and this is impaired by factors such as the lack of databases on exposure to medicinal products and on medical data during hospitalization.
Data Collection Each patient, or their relatives, was interviewed within 48 h of admission by a Lao medical doctor, trained to complete the study questionnaire developed for the purpose of this study, with a pharmacovigilance pharmacist. The questionnaire was developed in French and the questions were asked in the Lao language by the Lao medical doctor, who is fluent in French. The 40-questions questionnaire included sociodemographic, medical history and medication exposure data (see electronic supplementary material 1). It was tested with 39 patients enrolled in a feasibility study, to assess understanding and ease of completion. The respondents to the feasibility study were asked to tell if all the words were understood. A few minor corrections were made to the original questionnaire. A detailed prehospital medication exposure history for the 2 weeks preceding admission was taken through openended questions to record the name, dosage, place of procurement, if the medicine was obtained through self-medication, and the start and end dates of taking the medication.
The respondents were asked to show any medicines, prescriptions, health record booklets and/or referral letters. To minimize information bias, a questionnaire adapted from Roulet et al. [27]  was used to record self-medication history. Yaa chud use was also recorded. Medication was considered as chronic use if taken for C3 months. Medicines were classified on the basis of the Anatomical Therapeutic Chemical classification index  [28]. Patients were followed during the hospitalization and charts were reviewed again following discharge. Patients were subsequently contacted through telephone to ensure data completeness.