dataesr/scientific-paragraphs-categorization huggingface dataset:
Serum Biomarkers Data for HBV and HCV seropositivity, for AFP and C-reactive protein (CRP) levels and for liver function tests, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), albumin and total bilirubin were available and measured as previously described  (20). In addition, the ratio of AST/ALT and BARD score were calculated and used as markers of liver fibrosis  (22). BARD score, a non-invasive scoring system used to predict fibrosis severity in patients with non-alcoholic fatty liver disease, was calculated as the sum of BMI >28 = 1 point, AST/ALT >0. 8 = 2 points and diabetes = 1 point. Plasma concentrations of OPN were measured using a commercial ELISA kit from R&D Systems (Minneapolis, MN) as previously described  (8).
Potential effect modifications of the association between OPN levels and HCC risk by sex, age at recruitment, years of follow-up, baseline and lifetime alcohol consumption, and smoking status were evaluated in separate analyses by including interaction terms formed by the product of modifying variable categories and the values of OPN. The statistical models were adjusted for alcohol using a combination variable of alcohol intake at baseline (i. e. recruitment into the cohort) and alcohol drinking throughout life periods (at 20, 30, 40, 50 years of age). These data were derived from standardized/validated dietary and lifestyle questionnaires  (17). Participants classified as never drinkers indicated no alcohol intake at baseline, and no past alcohol intake. Former drinkers indicated no alcohol intake at baseline, but did have past alcohol intake.
Drinkers at recruitment indicated alcohol intake at baseline, but did not have past alcohol intake. Lifetime drinkers were defined as those who indicated alcohol intake at both baseline and prior. All the categories of alcohol exposures assessed are mutually exclusive. Statistical significance of interactions (p<0. 05) was assessed using likelihood ratio tests based on the models with and without the interaction terms. Sensitivity analyses were performed including additional adjustment and/or stratification by hepatitis status, AFP, BARD score, liver function tests, sex, years of follow-up and diabetes. P-values<0. 05 were considered statistically significant. Analyses were performed using Stata version 11 (StataCorp, College Station, Texas) and R software, version 3. 0. 2 (R Foundation for Statistical Computing, Vienna, Austria).
Financial Support: This work was supported by  NIH   R01 CA120719  to LB and by the  French National Cancer Institute (Institut National du Cancer; INCA)  grant number  2009-139  to MJ. The coordination of EPIC is financially supported by the  European Commission (DG-SANCO) ; and the  International Agency for Research on Cancer. The national cohorts are supported by  Danish Cancer Society (Denmark) ;  Ligue Contre le Cancer ;  Institut Gustave Roussy ;  Mutuelle Générale de l'Education Nationale ; and  Institut National de la Santé et de la Recherche Médicale (INSERM) (France) ;  Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) ; and  Federal Ministry of Education and Research (Germany) ;  Hellenic Health Foundation (Greece) ;  Italian Association for Research on Cancer (AIRC) ;  National Research Council ; and  AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy) ;  Dutch Ministry of Public Health, Welfare and Sports (VWS) ;  Netherlands Cancer Registry (NKR) ;  LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland) ;  World Cancer Research Fund  (WCRF); and  Statistics Netherlands  (the Netherlands);  European Research Council (ERC)  (grant number  ERC-2009-AdG 232997 ) and Nordforsk; and  Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway) ;  Health Research Fund (FIS) ;  Regional Governments of Andalucía, Asturias ,  Basque Country ,  Murcia  (No.
Methods We use CP-BOLD data from controlled canine (10) experiments imaged at rest, under baseline and severe LAD occlusion (ischemia). We delineate manually all myocardial borders to have ground truth. Based on these delineations we learn dictionaries (examples shown in Figure  1a ) to describe a given patch (a small square image block) with as few (ie. , sparse) linear combinations of templates as possible. The coefficients of those combinations form a feature vector for each patch, and can describe it while remaining unaffected by the BOLD contrast. We use such feature vectors for myocardial segmentation by optimizing a non-linear 1 The University of Edinburgh, Edinburgh, United Kingdom Full list of author information is available at the end of the article classifier but also for non-linear registration to correct for myocardial motion in this cine-type acquisition.
Methods Survey instrument. We conducted an online 28-item survey consisting of multiple choice and Likertscale questions (see Supplementary Table  S1 ). A short introduction specified that the survey was not addressing the use of gene expression profiling assays that evaluate the risk of recurrence in early breast cancer, such as OncotypeDx ® , Mammaprint ® and Prosigna ®. The first six questions captured demographic data and characteristics of the participants. The remaining 22 questions assessed different aspects of the use of tumor genome sequencing including frequency of use, context and reasons to use tumor genome sequencing, perceived utility of such testing, confidence in interpreting the results, accessibility and funding, and future perspectives. Skip logic was applied for questions 8-23 so that responders that had never used tumor genome sequencing in the past would not answer these questions.
Statistical analysis. Descriptive analysis was undertaken using Excel software from Microsoft Office. Multivariable logistic regression modeling was carried out to determine the relationship between predictors and either the use of tumor genome sequencing (Yes or No) or the expressed degree of confidence to interpret the results (high or not) using SAS software. Univariate analyses were conducted first and used to make a pre-selection of covariates to be tested in a multivariable setting. Only covariates that showed a p value < 0. 30 in the univariate model were considered for the multivariable model. For use of genome sequencing, a stepwise backward selection of covariates was applied to select the final model while a forward stepwise method was used for the other binary outcomes. Odds ratios were estimated and are reported with 95% confidence intervals and their statistical significance was tested using exact probability distribution.
Acknowledgements The authors would like to thank the  European Society for Medical Oncology (ESMO) ,  European School of Oncology (ESO) , the  Breast International Group (BIG) the Belgian Society of Medical Oncology (BSMO) , the  French Breast Cancer Intergroup UNICANCER (UCBG)  and the  Associazione Italina di Oncologia Medica (AIOM) Giovani  for circulating the survey through their network. The authors would like to thank all the participants who took the time to complete this survey.
Subjects were free to withdraw from the study at any time. They could also withdraw or be withdrawn if they experienced serious adverse events, if it was thought that continuing to participate in the study would compromise their health, or if they failed to comply with study protocol. The study was reviewed and approved by the relevant IRB, (16 janurary 2003-Comité de Protection des Personnes, Paris-Ile de France 5, Paris, France). It was conducted in compliance with local regulations and approved by the national advisory commission on databases computing personal information (Commission Nationale Informatique et Libertés). It complied with ICH GCP guidelines, and the Declaration of  Helsinki (1975 Helsinki ( , revised in 2000)).
Intervention, randomization and blinding, and examination schedule The study protocol has been previously described elsewhere  [19]. In brief, eligible subjects were randomized in a 1:1 ratio to receive 3 capsules daily containing 280 mg DHA each (Reti-Nat 1 , provided by Bausch & Lomb), the effective DHA dose being 840 mg/day, or placebo (602 mg olive oil-since there is no fatty acid with a "neutral" biological effect, olive oil was selected as the placebo because it is part of a staple diet and has no deleterious effect on the retina) for 3 years on an out-patient basis. QL-Ranclin software (Qualilab, France) was used to generate the randomized list prior to enrollment. The subjects and the study personnel were both blinded to the treatment assignment. Subjects were examined at baseline (Visit 1), 6 months (Visit 2), 1 year (Visit 3), 2 years (Visit 4), and 3 years (Visit 5).
At baseline, clinical and ophthalmologic examinations of potentially eligible subjects were checked against inclusion/exclusion criteria. Data recorded included socio-demographic information, relevant ocular and medical history, and concomitant treatment. Biological samples were collected at baseline examination before any supplementation. They included serum lipids and lipoproteins and genetic polymorphisms validated as genetic markers of exudative AMD. Genomic DNA was extracted from 10 mL blood leukocytes as previously described in AMD patients  [29]  and using the Illustra 1 kit according to the manufacturer's protocol (GE Healthcare) in controls. Genotyping of CFH rs1061170 and ARMS2/ HTRA1 rs10490924 alleles were performed by quantitative polymerase chain reaction allelic discrimination using reagents and conditions from Custom Taqman Single-Nucleotide Polymorphism Genotyping Assays (Applera, Corp, France), using ABI 7900HT (Applied Biosystems).
Finally, background leveling for a drusen image was combined with the well-known, histogram-based Otsu method  [36]  for background selection of input to the model and final threshold selection to achieve a largely automated method of drusen segmentation (Fig  2 )  [37]. This algorithm also extends to segmentation of reticular pseudodrusen aka reticular macular disease (Fig  3 ), and to images with co-existent geographic atrophy  (Fig 4). This model has been tested for accuracy and has also been implemented in autofluorescence images  [35, 38]. The model for automated drusen segmentation was developed within Matlab (Matlab 7. 0; The Mathworks, Inc. , Natick, MA) and the results are visualized in Adobe Photoshop, both of which are commercially available. We also applied it from a free-standing graphical user interface that does not require any other software.
Difference for gender, smoking and CFH and ARMS2 polymorphims between DHA and placebo group was assessed by Chi² test. (Table  1 ). We compared drusen characteristics between baseline and 3 years according to treatment group (DHA vs. placebo) using paired T test. (Table  2 ). Associations of DHA supplementation with drusen remodeling were estimated using linear regression adjusted for age and gender. 3-year drusen remodeling data were used as the dependent variables and the treatment group (DHA or placebo), age and gender as the independent variables. Because we studied 3 drusen characteristics in 4 different locations, we used the Bonferroni's correction for multiple tests; p<0. 005 was considered as significant. (Table  3 ). Associations of 3-year drusen number, diameter and area remodeling in each location with socio-demographic and genetics characteristics were estimated using Pearson correlation for age, Student's t Test for gender and smoking and ANOVA for CFH and ARMS2 polymorphisms.
Data Sets Analyzed Among the 300 randomized subjects, a total of 298 subjects were included in the Safety Set (150 subjects in the DHA group and 148 in the placebo group). The FAS (all subjects in the safety set with at least one post-baseline assessment of CNV) consisted of 134 subjects in the DHA group and 129 in the placebo group. After exclusion of subjects with major deviations (mainly for premature withdrawal), the PPAS, those in the FAS population without a major deviation from the protocol that could jeopardize the primary outcome, included 121 subjects in the DHA group and 111 in the placebo group (Fig  1 ). In the PPAS population, drusen progression was analyzed in those subjects that did not develop CNV, counting for overall 167 patients, 87 that received DHA and 80 that received placebo.
17; p = 0. 003). Women tended to show a greater reduction in total drusen diameter in the inner subfield with the CFH polymorphism (TT) genotype than with the heterozygous or homozygous risk alleles (CT\CC) (p = 0. 03), Concerning drusen area remodeling, we found that drusen area in the inner subfield was also reduced in older patients (r = -0. 17) and in women (p = 0. 01), but these associations did not reach statistical significance. No association was found between any drusen remodeling variable in the middle or outer subfields or the <6000 μm diameter field and any socio-demographic and genetic characteristics (Table  4 ). We also analyzed drusen remodeling according to EPA and DHA measured in serum and in red-blood cell membranes. We found no significant results (data not shown). Additionally, we analyzed drusen remodeling in concordance with development of geographic atrophy.
Analysis of anti-HBsAg, anti-E1 and anti-E2 antibody responses Anti-HBsAg antibodies were quantified with the ARCHITECT system (Abbott Laboratories). Anti-E1 and anti-E2 responses were evaluated with "in-house" ELISAs, based on the use of solid phases consisting of lysates of baby hamster kidney (BHK-21) cells expressing HCV E1 or E2 proteins, which were compared with control cells expressing ß-galactosidase (ß-gal). For these experiments, the DNA sequences encoding HCV E1 or E2 envelope glycoproteins derived from a genotype 1a HCV isolate (isolate Dj) were therefore cloned into an original eukaryotic DNA expression vector (pSFV) based on the Semliki Forest Virus replicase complex, which present a high level of expression efficiency. These DNA sequences, amplified from the previously described pSFV-HCVdj plasmid (Genbank AF529293) encoding the core-E1-E2 sequence of a genotype 1a HCV  [28] , also contained the upstream signal sequence responsible for translocation of the E1 or E2 ectodomain into the endoplasmic reticulum lumen (amino acids 166-191 from the HCV core protein in the HCV polyprotein for E1 and amino acids 370-383 from the HCV E1 protein in the HCV polyprotein for E2)  [29, 30].
(B), An immunoassay using human monoclonal antibodies recognizing conformation-dependent discontinuous epitopes on the E2 protein (AR3A) and the folded E1-E2 complex (AR5A) demonstrated the productive folding and heterodimerization of HCV envelope proteins in the context of fusion proteins. The monoclonal antibodies AR3A and AR5A were added to ELISA wells coated with chimeric particles (S, S+E1-S, S+E2-S, S+E1-S+E2-S or a S+E1-S/S+E2-S mixture; 25 μg/ml) or JFH-1 WT viruses purified on sucrose cushions (1,000 focus-forming units; positive control: gray histogram) captured with a lectin precoating. Specific binding was detected with monoclonal peroxidase-conjugated mouse anti-human immunoglobulin antibody. Absorbance at 490 nm was determined. The data shown are the means ± standard deviation of one experiment performed in quadruplicate.
Acknowledgments We would like to thank  Dr. Takaji Wakita  for the JFH-1 virus strain,  Dr. Jens Bukh  for the chimeric JFH-1 genomes  H77/JFH1 ,  J4/JFH1 ,  S52/JFH1  and  ED43/JFH1 ,  Dr. Charles Rice  for the Huh7. 5 cell line,  Dr. Jean Dubuisson  for the mAb H52,  Dr Harry Greenberg  for the mAb A4,  Dr. Camille Sureau  for the polyclonal anti- HBs Ab ,  R247 , and  Dr. Mansun Law  for the mAbs,  AR3A  and  AR5A.
This study was supported by the  "Hepatibivax" grant from the "Emergence" program  of the  Agence Nationale pour la Recherche (ANR, France , grant  ANR-11-EMMA-026 ), the  Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS, France , grant  2014-1 ), the  Ligue contre le Cancer  ( Comités de l'Indre et Loire, du Maine et Loire, de la Sarthe, France ), and the  Académie Nationale de Médecine, France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Background: Interleukin 6 (IL-6) signaling plays a key role in the pathophysiology of rheumatoid arthritis (RA) and is inhibited by sarilumab, a human monoclonal antibody blocking the IL-6 receptor alpha (IL-6Rα). The effects of sarilumab plus methotrexate (MTX) on serum biomarkers of joint damage and bone resorption were assessed in two independent studies (phase II (part A) and phase III (part B)) of patients with RA with a history of inadequate response to MTX from the MOBILITY study (NCT01061736). Methods: Serum samples were analyzed at baseline and prespecified posttreatment time points. Biomarkers of tissue destruction, cartilage degradation, and synovial inflammation were measured in part A; assessment of these markers was repeated in part B and included additional analysis of biomarkers of bone formation and resorption (including soluble receptor activator of nuclear factor-kB ligand (sRANKL)).
The efficacy and safety of sarilumab in combination with methotrexate (MTX) in patients with moderate-to-severe RA and inadequate response to MTX (MTX-IR) were evaluated in the two-part (phase II (part A) and phase III (part B)) MOBILITY trial (NCT01061736)  [24, 26]. In MOBILITY A and B, patients treated with sarilumab demonstrated statistically significant improvements in American College of Rheumatology 20 % (ACR20) response rate at weeks 12 and 24, respectively. In MOBILITY B, patients treated with sarilumab also demonstrated significant improvements in least squares mean change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 16 and mean change in the van der Heijde modified total Sharp score (mTSS) at week 52, relative to placebo + MTX. The erosion score (ES) and joint space narrowing (JSN), components of the mTSS, were significantly reduced compared with placebo + MTX as early as week 24.
Study design The results of MOBILITY (NCT01061736), a two-part (phase II (part A) and phase III (part B)), randomized, double-blind, placebo-controlled, multicenter study that evaluated the efficacy and safety of subcutaneous sarilumab in combination with MTX in patients with active RA and MTX-IR have previously been described  [24, 26]. Part A of MOBILITY was a 12-week, phase II, dose-ranging study in patients with active RA who were randomized to receive MTX in combination with placebo or one of five subcutaneous sarilumab doses  [26]. Patients who participated in part A were not eligible for part B, a 52-week, phase III study evaluating the safety and efficacy of sarilumab 150 mg and 200 mg every 2 weeks (q2w) in combination with MTX  [24]. The protocol was approved by the appropriate ethics committees/institutional review boards (see "Acknowledgments" for details), and all patients provided written informed consent before study entry.
Sarilumab 200 mg q2w was chosen for these analyses because this dose demonstrated better efficacy compared with sarilumab 150 mg q2w with respect to the bone and joint x-ray outcomes (i. e. , mTSS, ES, and JSN) in MOBILITY part B, and the additional biomarkers measured reflect pathological processes associated with these scores. To be selected for this retrospective biomarker analysis, patients were required to have baseline, week 2, and week 24 biomarker samples and week 24 radiographic data available. Patients were included in the analyses if the baseline value and at least one postbaseline value were available for at least 1one biomarker under evaluation. Starting at week 16 in MOBILITY part B, patients with a lack of efficacy could be "rescued" by switching to open-label sarilumab 200 mg q2w + MTX.
An unstructured covariance structure was assumed in all models. The Bonferroni correction was used to adjust P values for multiplicity. A P value <0. 05 after adjustment was considered significant. For exploratory purposes, percent changes from baseline in biomarkers and sRANKL/OPG were also compared between responders and nonresponders (patients who achieved or did not achieve ACR50 or low disease activity (LDA), as measured by 28-joint disease activity score by CRP (DAS28-CRP) <3. 2) at week 24 using similar methods and after adjustment for baseline values, separately by treatment group; nominal P values are reported. Analyses were performed using SAS ® v9. 2 or higher (SAS Institute, Cary, NC, USA).
Acknowledgements This study was sponsored by  Sanofi  and  Regeneron Pharmaceuticals, Inc. Editorial assistance was provided under the direction of the authors by  Gretchen Chidester, PhD ,  MedThink SciCom , and funded by  Sanofi and Regeneron Pharmaceuticals, Inc. The authors thank  Dr Emmanuelle Cousin ,  Ling Cai , and  Xin Zhang  for their assistance with data analysis and interpretation and  Drs Hubert van Hoogstraten  and  Paul Cavanaugh of Sanofi  for their critical review of the manuscript. The specific ethical bodies that approved study EFC11072-part B are as follows: CIE Para Ensayos en  Farmacologia Clin Prof Dr Luis M. Zieher Jose E. Uriburu ,  Buenos Aires ;  CIEIS -Italiano De Cordoba Roma, Córdoba; Comité de Etica Instituto Strusberg, Córdoba; CIEM-NOA Las Piedras, Tucumán; CIEFA Uruguay, Buenos Aires ;  Instituto De Investigaciones Clínicas Zarate F.
Tolerability was also assessed in a phase I trial in patients with advanced solid tumors and hematological neoplasms (NCT00559533), and results are pending. Based on their mechanisms of action, RG7112 and other agents in this class might be effective in patients with MDM2 amplification and wild-type TP53 tumor. However, studies to test this hypothesis have not been broadly performed in large numbers of genetically characterized patient derived cell lines or in the clinical trials performed to date. The study presented here aims to test the therapeutic activity of RG7112, a member of MDM2/Nutlin (cisimidazoline) inhibitors  [13] , in GBM patient-derived cell lines (PDCL) and animal models of GBM carrying various alterations of the core p53 pathway (MDM2 amplification, MDM4 amplification, TP53 mutation).
Statistical analysis All statistical data were collected using GraphPad Prism software (San Diego, CA). For protein and RNA level comparisons, p-values were calculated by comparing data measured from 3 independent experiments from each individual cell line with data from all the other cell lines. Parametric analysis was done using standard error of the mean, mean and n, in a multivariate one-way analysis (ANOVA) with Tukey's post-tests for multiple comparisons, and Student t-test for single comparisons. All data are shown as mean ± S. E. M. *p-value < 0. 05; **p-value < 0. 01; ***p-value < 0. 001; ****p-value < 0. 0001. Overall survival was defined as the time between histological diagnosis and death or the last follow-up. Patients who were still alive at the last follow-up were considered as a censored event in the analysis.
MDM2 amplification does not impact prognosis in newly diagnosed GBM patients and is maintained at tumor recurrence Data sets from the 2013 GBM TCGA database  [4]  (publically available on cBio portal; MSKCC) were extracted and analyzed. TP53, MDM2 and MDM4 were found to be genetically altered (i. e. gene copy number or sequence abnormalities) in 22%, 9% and 9%, respectively, of GBM from TCGA 2013 database. Graphs can be seen in supplementary data (S1). MDM2/MDM4 alteration with concurrent TP53 mutation was found to be a rare event detected in 1. 37% of cases. Moreover, MDM2 and MDM4 amplifications were found to be mutually exclusive. Finally, as expected, MDM2 mRNA was found to be overexpressed in MDM2-amplified tumor (S1). From the OncoNeuroThèque database, 696 newly diagnosed GBM with genomic profiling and clinical annotations were identified.