dataesr/scientific-paragraphs-categorization huggingface dataset:
■ ACKNOWLEDGMENTS This research received financial support from the  European Union 's  Horizon 2020 research and innovation program  under grant agreement no. 875629  (NAIMA) and  M-ERA. NET network  and  Slovenian Ministry of Education, Science, and Sport  with the  NOEL  project. We further acknowledge financial support from the  Slovenian Research Agency  (research core funding  P2-0423 ,  P2-0393 ,  P1-0201 ,  P1-0175 , and projects  N2-0266  and  N1-0139  ' Delamination of Layered Materials and Structure-Dynamics Relationship in Green Solvents '). M. T. and A. J. are most grateful to  Prof. Otto Glatter  for his generous contribution to the instrumentation of the  Light Scattering Methods Laboratory in Ljubljana. CENN Nanocenter Slovenia  is also acknowledged for using an FIB-SEM instrument Helios NanoLab 650.
(Arg809Ter) -that would lack part of the scavenger receptor domain and the trypsine-like serine protease catalytic domain. All 30 copper cats were T/T homozygous for the variant, which was also found in 20 C/T heterozygous British control cats but was absent in 340 cats from the 99 Lives dataset. Finally, genotyping of 218 cats from 12 breeds failed to identify carriers in cats from other breeds. We propose that this third CORIN:c. 2425C>T variant represents the wb BSH (British recessive wideband) allele in the domestic cat.
However, careful examination of pedigree data indicated a probable autosomal recessive inheritance pattern. DNA and phenotypic data from these copper British cats and from control cats were collected. Twenty-five British cats (including 10 copper cats) were genotyped using the Illumina Feline 63 k SNP array, among which 60 599 SNPs yielded usable results (minor allele frequency >5%, genotyping rate >95%). All 25 cats had genotyping rates >95% and all were conserved for the analysis. Following basic case-control analysis, the genomic inflation factor was 1. 59 and the 25 highest significant associations were identified for 25 SNPs, among which 18 markers were located on chromosome B1 (Appendix S1, Figure  1e , Table  S1 ). After Bonferroni correction of the P raw values for multiple tests, no SNP had a significant P Bonferroni value (Figure  1e , Table  S1 ).
AC K NOW L E DGE M E N T S The authors wish to thank the 99 Lives Cat Genome Consortium for sharing feline genome sequence information and Caroline Dufaure de Citres (Antagene) for technical assistance. The authors thank the owners, breeders and feline judges for providing samples, hairs and pictures, especially Elizaveta Lipovenko, Linda Petersson-Wahlqvist and Eleonora Ruggiero for their great help. Feline DNA samples are part of the Feli-DNA biobank, which is part of the CRB-Anim infrastructure (ANR-11-INBS-0003, in the framework of the 'Investing for the Future' program, PIA).
External validation of a risk score model for predicting major clinical events in adults after atrial switch Introduction A risk model has been proposed to provide a patient individualized estimation of risk for major clinical events (heart failure events, ventricular arrhythmia events, all-cause mortality) in patients with transposition of the great arteries corrected by an atrial switch operation (D-TGA). The aim of this study was to externally validate the model. Methods A retrospective, multicentric, longitudinal cohort of 417 patients with D-TGA (median age 24 years [interquartile range 18-30], 63% male) independent of the model development and internal validation cohort was studied. Data on risk model predictors (age > 30 years, prior ventricular arrhythmia, age > 1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction) were collected from the time of baseline clinical evaluation.
Patients were treated as nonresponders after the time of discontinuation up to the visit they would have reached if they had stayed in the study up to the time of data cutoff (May 2019). For ongoing patients, no imputation for visits that they had not reached by the data cutoff was applied and other missing data were imputed as nonresponse. Last observation carried forward imputation was applied after a patient advanced to a subsequent study up to the visit they would have reached if they had stayed in the study. Safety. Safety end points evaluated included: adverse events (AEs); serious AEs; and AEs of special interest (AESI), which included serious infection events (infections meeting serious AE reporting criteria), opportunistic infections (excluding tuberculosis and herpes zoster within a single dermatome or 2 adjacent dermatomes), herpes zoster, malignancies (excluding nonmelanoma skin cancer [NMSC]), NMSC, gastrointestinal perforation, major adverse cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE).
Data Sharing Statement On request, and subject to certain criteria, conditions, and exceptions (see https://www. pfizer. com/science/ clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual deidentified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines, and medical devices for indications that have been approved in the United States and/or European Union or in programs that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The deidentified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal.
Supplementary Material In brief, the trials included: A double-blind, placebo-controlled, dose-ranging phase 2 induction trial (NCT00787202) in which patients were randomized to receive tofacitinib at a dose of 0. 5 mg, 3 mg, 10 mg, or 15 mg, or placebo BID for 8 weeks. 1  Two identical phase 3 induction trials (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951) in which patients were randomized to receive tofacitinib 10 mg or placebo BID for 8 weeks. 2  A phase 3 maintenance trial (OCTAVE Sustain, NCT01458574) enrolling clinical responders from OCTAVE Induction 1 or 2. Patients were rerandomized to receive tofacitinib 5 mg or 10 mg BID, or placebo BID for up to 52 weeks. 2  An ongoing open-label, long-term extension trial (OCTAVE Open, NCT01470612) enrolling patients who completed OCTAVE Induction 1 or 2 without a clinical response, and patients who completed or were treatment failures in OCTAVE Sustain.
OCTAVE Open data are as of May 27, 2019 (database not locked) per local read of endoscopy. Nonresponder imputation was applied after a patient discontinued and last observation carried forward imputation was applied after a patient advanced to a subsequent study up to the visit they would have reached if they had stayed in the study. No imputation for missing data was applied for ongoing patients except nonresponder imputation for intermittent missing data. a Total of 16 weeks' induction treatment with tofacitinib. b Delayed responders achieving clinical response at Week 8 of OCTAVE Open, as a proportion of the overall tofacitinib 10 mg BID induction study population (n/N1). c Patients achieving clinical response at Week 8 of OCTAVE Induction 1 and 2, as a proportion of the overall tofacitinib 10 mg BID induction study population (n/N1).
Methods We restrospectively included all consecutive patients who had a positive JAK2V617F mutation referred to Amiens University Hospital between December 2008 and September 2016. Inclusion criteria were a positive JAK2V617F mutation with at least 1% of allele burden, with or without confirmed MPN. In cases of suspected MPN or unexplained venous or arterial events laboratory analysis to confirm the presence of the JAK2V617F mutation was requested. Exclusion criteria were the presence of acute leukemia, age under 18 years and absence of informed consent. All data were extracted from medical records. At diagnosis, epidemiological characteristics, date of positive JAK2V617F mutation diagnosis and the allelic burden, and cardiovascular risk factors were collected. At follow-up visits, all VTE and CVE events, anticoagulant and/or antiplatelet therapy, and cyto-reductive treatment(s) were noted.
From these Fine and Gray subdistribution models, sub-hazard ratios (SHR) and their 95% CI were estimated. Potentially prognostic covariates such as thrombotic events before diagnosis or thrombotic treatments (antiplatelet or anticoagulant therapy before diagnosis) were included in a multivariate competing risk regression model. Depending on the outcome, a Fine and Gray competing risk regression was computed to assess the interaction between JAK2 mutation burden and type of first event (venous or arterial thrombosis). A significant interaction indicated the need for a subgroup analysis according to first thrombotic event. All the tests were two-sided, with a significance level of 5%. Statistical analyses were performed using R software, version 4. 0. 4. ©2021 (The R foundation for Statistical Computing, Vienna, Austria), with "tableone", "survey", "car", "sandwich", "survival" and "cmprsk" packages.
tumour responses in paediatric phase I and II trials  [16, 17]. To assess the probable effect of changing the current approach, the MOA of 89 drugs granted a class waiver by the EMA between June 2012 and June 2015 were assessed to determine if they might be active against potential paediatric therapeutic targets. Forty-eight (54%) had a MOA warranting paediatric development. Two (2%) drugs were considered not to be relevant and 16 (18%) required further data to be informative  [7]. The Working Group proposed a MOA-based approach with five initiatives, which all have been implemented to some degree (Table  2 )  [18]. The revision of the 2015 class waiver list by the EMA came into effect in 2018  [19]. Eight class waivers which had been given because the diseases did not occur in children were revoked, including two for cancer, and 15 revised.
Fit for Filing The Fit for Filing Working Group aims to develop the best principles for how to design and deliver an academic clinical trial with a dataset that meets the expectations for inclusion in a regulatory package. There is multi-stakeholder involvement with co-leaders from representatives of industry and academia. The ultimate aim is to improve the implementation of investigatorinitiated-trials in intent to file, i. e. facilitating the use of the data for regulatory purposes when relevant. In the past, academic sponsored trials have been frequently found not to be 'fit for purpose' when they have been subsequently included in regulatory submissions to support application for marketing authorisation. The Working Group has identified key general principles: (i) early planning is essential with early communication amongst academic research consortia, pharmaceutical industry and regulators; (ii) prospective collaboration and agreements; (iii) alignment of data collected to meet study objectives and regulatory commitments; (iv) recognition of shared responsibilities.
The registry will focus on licensed drugs with or without market authorisation for use in children with cancer. Compound use can be in completed clinical trials, commercial, off-label use and/ or compassionate use. The registry will rely on healthcare providers submitting data to the registry, so-called 'secondary data use', of already existing and collected data and will not require the generation of new data. A core dataset to be entered for all drugs has been developed. The registry will be developed with regulatory input (e. g. through Qualification Procedure from the EMA and FDA) how to fulfil post-marketing regulatory requirements. This ongoing project will create an asset that will follow children and adolescents exposed to innovative medicines long-term.
However, currently there are children who receive innovative medicines outside clinical trials and the related data are not captured  [48, 49]. Furthermore, these data should be made available for prescribers and families and useable for regulatory purposes. When data are collected and analysed from patients who have received an innovative drug, a negative signal in a given indication could support no further use or formal evaluation of the drug; in contrast, a positive signal would strongly support a formal evaluation in a clinical trial and further development. An ACCELERATE multi-stakeholder position article will describe the challenges and obstacles of the use of RWE, when RWE is not an appropriate replacement for trials and indicating the circumstances when the use of RWE may be appropriate.
Ongoing actions to raise Ongoing awareness to the professionals involved in trial design and approval and the general public Fit for Filing To develop the best principles on Consensus of a model for Achieved how to design and deliver an investigator-initiated clinical academic clinical trial with a dataset that can be included in a package for marketing authorisation trials of new drugs to meet the regulatory requirements through the 'Fit for Filing' Educational strategy to pro- Planned mote this approach Long-term follow up To develop international, open, Agreed concept proposal and Achieved harmonised, and sustainable data proposed structure and gover- registry to collect long-term side effects of new anti-cancer therapies in children nance of registry [40] with the aim to create the reg-Implementation of project Ongoing istry has commenced International cooperation Identify the obstacles to inter- Review of intercontinental Achieved continental cooperation and clinical trials completed [43] collaboration Data survey of interconti- Ongoing Develop principles and best nental trials to identify practices for global clinical to obstacles enable paediatric oncology Planned (continued on next page).
J * V = J V ρ 1 2 V g D h ρ L -ρ g -1 / 2 Although flow boiling in offset-strip fins and the use of binary mixtures have been investigated in the literature, they have been studied separately. There is thus a lack of research combining simultaneously offset-strip finned geometries and binary mixtures. It is the main goal of the present paper. The present paper discusses all the experimental observations mentioned above and introduced in the literature by visualizing the upward vertical two-phase flow in offset-strip fins of a binary mixture containing R-134a and R-245fa under various conditions of pressure and mass flux. The data of heat transfer coefficient and pressure drop are collected. A new correlation of pressure drop is proposed.
(  8 ). The second approach is used when the homogenous model is not applicable (low mass fluxes, low pressure values). It is called the drift flux model proposed by Zuber and Findlay  [ 11 ]. In this case, void fraction is determined with either measurement devices or using predictive methods. In the present work, correlations are used to estimate void fraction along the test section. Besides, the frictional pressure gradient could be correlated to the liquid-phase pressure drop. The latter is corrected by L named liquid twophase multiplier. Therefore, the two-phase frictional pressure drop can be estimated using Eqs. (  10 )-  (12)  : dP dz Frictional = ( L ) 2 dP dz L ( 10 ) dP dz L = - 4 f L D h 1 2 G 2 L ρ L (11) R e L = G L D h μ L = ( 1 -x ) G D h μ L (12) None of the existing correlations in the literature for liquid twophase multiplier could predict the experimental data obtained in the present work.
Acknowledgments The authors thank the veterinary staff of  Institute S. Vincent-Naulleau  and  V. Neuville  and  Animalliance  for taking care of the mice;  N. Dechamps  for cell sorting; and  V. Menard  for assistance with irradiation. The authors also thank  Kenji Kohno  and  Masato Tanaka  for acceptance of the use of CD169 DTR/DTR mice;  F. Ferri  and  D. Lewandowski  for help and support; and  N. Gault  for help and critical reading of the manuscript. This work was supported by the  IRBIO/CEA program  and  INSERM. The fourth year of M. C. 's thesis was funded by the  Medical Research Foundation (FRM).
The African Cancer Registry Network (AFCRN), which includes all population-based cancer registries in SSA with relatively complete recording, provides a good source of data to determine the epidemiology of cancer in SSA. 5  In the present study, we examine trends in ovarian cancer incidence in 12 cancer registries from four regions in SSA for periods between 10 and 34 years, with particular interest in the trends by histological subtype. Given the limited data on OC incidence in SSA, the current study will provide useful information on this important cancer of women, to inform policy makers and health professionals on the current burden of the disease and its likely future evolution, and so help in the development of strategies for early diagnosis and clinical care of OC.
| METHODS Twelve population-based cancer registries in 11 countries, members of AFCRN, were included in the study: Kenya (Nairobi), Mauritius, Seychelles, Uganda (Kampala), Congo (Brazzaville), Zimbabwe (Bulawayo and Harare), Cote d'Ivoire (Abidjan), The Gambia, Mali (Bamako), Nigeria (Ibadan) and South Africa (Eastern Cape). All are population-based, recording data in defined populations whose composition by age, and sex is known. The methods of data collection, validation and storage in these registries are described elsewhere. 5 e registries selected for the study were those that could provide estimates of the incidence of cancer of the ovary of consistent quality for periods of 10 or more years. Quality of the registration process was evaluated as described in Chapter 3 of Parkin et al.
5  Cases of ovarian cancer (ICD-10, C56. 9) were abstracted from the database of the AFCRN, along with the estimated populations at risk by age group, and ethnicity, where appropriate. Population data were derived from census estimates, and inter-censal estimates were calculated assuming an exponential growth rate between censuses. Annual age specific, crude and age standardised rates were calculated, with age standardisation carried out by the direct method using the "world standard population. "  13 arian cancers were further classified as Epithelial, Germ Cell tumours, Sex cord-stromal tumours, Other specified types and Unspecified, according to the ICD O-3 morphology codes, as described in table 4. 9 of chapter 4 (Histological Groups) of Bray et al (Table  1 ). 14 ses without morphological proof of diagnosis were classified as Unspecified (Group 5), although in some registries, some of these cases had been coded as "Carcinoma NOS" (ICD-O 3 code 8010).
For those datasets/periods retained, we investigated trends in annual age standardised rates, fitting regression lines to determine whether the trends (best fit of the regression) were best explained as linear, exponential or polynomial. For registries for which there was a poor fit of a simple exponential trend (R 2 <. Carlo permutation method. 15 r two datasets with discontinuous data over a very long time period (Bulawayo and Abidjan) we compared incidence rates for two separate time periods. For Seychelles, although data were available for a continuous 13-year period, numbers were sparse (45 cases in total), so we present age specific rates for two adjacent time periods. We calculated some conventional indicators of data quality  16, 17  -the percentage of cases with morphological verification (histology or cytology) of diagnosis (MV%) and the percentage of cases registered by death certificate only (DCO%)-for the time periods under review.
Nivolumab was subsequently approved for second-line treatment of advanced non-squamous NSCLC in the US (October 2015) and the European Union (June 2016), with PD-L1 expression conferring improved efficacy. In July 2015 and October 2015, respectively, the EC and the FDA granted approval for pembrolizumab as second-line treatment for patients with PD-L1 positive (≥1%), advanced NSCLC. Atezolizumab received approval from the FDA and the EC in October 2016 and September 2017, respectively for second-line treatment of advanced NSCLC, regardless of PD-L1 status. In CheckMate 017 (NCT01642004), a randomized phase 3 trial among previously treated patients with advanced squamous NSCLC regardless of PD-L1 expression level, median overall survival (OS) with nivolumab was 9. 2 (95% confidence interval (CI); 7.
3-13. 3) months compared to 6 (95% CI; 5. 1-7. 3) months with docetaxel  [2]. Similarly, in CheckMate 057 (NCT01673867), a randomized phase 3 trial among previously treated patients with advanced non-squamous NSCLC, median OS with nivolumab was 12. 2 (95% CI: 9. 7, 15. 0) versus 9. 4 (95% CI; 8. 0-10. 7) months with docetaxel, with PD-L1 expression providing increased efficacy  [3]. In the KEYNOTE-010 trial of previously treated, ≥1% PD-L1 positive, advanced NSCLC patients with squamous or nonsquamous histology, median OS was 10. 4 (95% CI: 9. 4, 11. 9) months for pembrolizumab 2 mg/kg and 12. 7 (95% CI:10. 0, 17. 3) months for pembrolizumab 10 mg/kg, versus 8. 5 months (95% CI: 7. 5, 9. 8) for docetaxel  [4]. In the OAK trial that enrolled advanced NSCLC patients regardless of histology and PD-L1 status, median OS was 13.
Since key studies describing IO use were presented at some congresses held between August 2019 and December 2019, such as the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer World Conference on Lung Cancer (IASLC WCLC), data from these conferences were extracted and included once available. Authors were contacted when additional information was needed. Studies were eligible for inclusion in the SLR if they included adults (18 years of age and older) who were previously treated with first-line anti-cancer therapy for locally advanced (stage IIIB or IIIC), metastatic (stage IV) or recurrent NSCLC. Key interventions of interest were IOs, specifically: nivolumab, atezolizumab or pembrolizumab; however studies with unspecified ICIs were also eligible for inclusion.
After removal of studies that did not pass this initial screening, full-text articles were then reviewed. Key data for all studies that met the inclusion criteria for the SLR were extracted, including study design, baseline patient characteristics and effectiveness endpoints (OS, PFS, response rate). Data were extracted as available in the publication/abstract and for the following key subgroups of interest: histology, PD-L1 expression, age, Eastern Cooperative Oncology Group (ECOG) PS, and presence of brain metastases and liver metastases. While baseline data for smoking status and driver mutations (such as epidermal growth factor receptor or EGFR) were extracted, inadequate reporting of OS estimates for these variables precluded the analysis of outcomes in these subpopulations. The data extraction was independently verified and validated by a second extractor against a clean copy of the publication or conference abstract.
6-41. 9) and 23. 9% (95% CI; 19. 8-28. 4), respectively. Within the non-IO group, the shortest median OS of 1. 1 months was reported in a small Japanese subpopulation (N = 36) receiving only best supportive care  [28] , while the longest median OS of 29. 3 months was reported in a subpopulation of a US Flatiron Health database study that received sequential targeted-/IO-based treatment  [29]  (Fig. 2 ). The median OS for mixed ICIs including nivolumab, pembrolizumab, atezolizumab, durvalumab, and unspecified ICIs, ranged from 4. 6 months  [30]  to 29. 6 months  [31]  (Fig. 2 ). The pooled estimate for mixed ICIs was calculated as 43. 9% (95%CI; 39. 1-48. 8) for 1-year OS rate (Table  2  and Fig. 3 ), and as 20. 4% (95%CI; 14. 7-27. 6) for 2-year OS rate (Table  2  and Fig. 4 ). In addition, Nadler et al  [21]  reported a 3-year survival rate of 17.