dataesr/scientific-paragraphs-categorization huggingface dataset:
A systematic analysis of the World Health Organization pharmacovigilance database confirmed a 32. 5% of mortality in patients who had myocarditis associated with the administration of ICIs with a median time-to-onset of 33 days (10). The increased reports of cases in the last years are perhaps consistent with growing recognition of this new clinical syndrome, as well as the more widespread use of ICIs. High-dose IV corticosteroids and withdrawal of ICI are considered the first-line therapy  (1, 91, 92) , while alemtuzumab (anti-CD52 antibody), antithymocyte globulin (anti-CD3 antibody), and abatacept (a CTLA-4 agonist) have been proposed in corticosteroid-resistant forms (Figure  1 )  (87, 93, 94). Retrospective data suggest that earlier (within the first 24 h) and high doses (501-1,000 mg/day) of corticosteroids lead to an improved outcome (95).
J Am Coll Cardiol. (2003) 42:466-72. doi: 10. 1016/S0735-1097(03)00648-X 17. Veronese G, Ammirati E, Chen C, Klingel K, Suzuki M, Okumura T, et al. Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis. Int J Cardiol. (2021) 324:131-8. doi: 10. 1016/j. ijcard. 2020. 10. 063 (2020) 141:2031-18. (2021) 26:553-78:736-45. doi: 10. 1136/annrheumdis-2019-215089 4. doi: 10 19:281-8. doi: 10. 1007/s10238-019-00565-8 A, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. (2018) 19:1579-89. doi: 10. 1016/S1470-2045(18)30608-9 10. Nguyen LS, Cooper LT, Kerneis M, Funck-Brentano C, Silvain J, Brechot N, et al. Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database.
Phylogenetic Analysis Single nucleotide polymorphisms were obtained using the Bionumerics software, version 7. 6 (AppliedMath, Belgium). Identified SNPs were selected according to strict criteria of the wgSNP module as follows: they had to be present on at least five reads in both forward and reverse directions, twelve base pairs had to separate them, they were not present in repetitive regions of the genome, and ambiguous SNPs [at least one unreliable (N) base, ambiguous (non-ATCG) base, or gap] were not included. The evolutionary trees were inferred on Mega  (Kumar et al. , 2016)  using the maximum likelihood method (Hasegawa-Kishino-Yano model) based on concatenated and validated SNPs (panel 1, 8,981 SNPs for 81 genomes; panel 2, 124 SNPs for 93 genomes). The trees were drawn to scale, with branch lengths measured in the number of substitutions per site.
IS6110 Distribution Analysis ISMapper (version 2. 0. 1) pipeline  (Hawkey et al. , 2015)  was carried out in this study for IS6110 identification on genome short-read sequences using Mb3601 reference genome  (Branger et al. , 2020). The employed script is available on GitHub. 2 To achieve 100% detection with high confidence, average genomewide read depths of < 75 × were excluded for panel 2 strains  (Hawkey et al. , 2015). Only 93 genomes (with Mb3601 reference strains) out of the initial 147 passed the quality selection described in this and the previous section. For uncertain IS6110 presence and/or localization (37 and 9 uncertain insertion sites in panel 1 and panel 2, respectively) due to low read depth in the IS insertion site, IS6110 presence was manually checked with Integrative Genomics Viewer  (Robinson et al.
Open access Description of the intervention During both study periods, patients presenting to the ED for chest pain are assessed for eligibility. Patients meeting all the inclusion criteria and none of the exclusion criteria receive verbal and written information about the study. They are included if they provide consent. The data needed to compute the HEAR, HEART and TIMI risk score for unstable angina are prospectively collected by the consultant, either in a secured electronic case report form (e-CRF) or in a printed version of the CRF.
Acknowledgements We would like to thank the  Groupement Interrégional pour la recherche Clinique du Grand Ouest (GIRCI-GO)  and the  HUGO  network for funding the study. We also wish to thank  Ms. Béatrice Gable ,  Ms. Cindy Augereau ,  Ms. Chloé Ragueneau ,  Ms. Barbara Maquin ,  Ms. Nadia Ben Rabah  and  Ms. Sandra Merzeau  for coordinating the project. We thank the  department of Innovation and research of the University Hospital of Angers  for its contribution. We thank  Mr. Jean-Marie Chrétien  for coordinating the development of the eCRF and the data management. We finally wish to thank the participating centres for their involvement in the study:  department of emergency medicine of the University Hospital of Angers, department of emergency medicine of the university clinics of Saint-Luc, department of emergency medicine of the University Hospital of Tours, department of emergency medicine of the University Hospital of Toulouse, emergency medicine of Le Mans Hospital, emergency medicine of Cholet Hospital, department of emergency medicine of the University Hospital of Liege, emergency medicine of Saint-Brieuc Hospital, emergency medicine of Saint Malo Hospital and emergency medicine of Vendée Hospital.
Background. The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. Methods. Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. Results. The standardized incidence of KRT was stable [annual percentage change (APC): -1.
INTRODUCTION Worldwide the number of patients on kidney replacement therapy (KRT) has been estimated at 3. 9 million in 2017, with the highest prevalence in high-income regions like Europe, North America and Japan [1-3]. In the first decade of this century, after years of continuous growth, the KRT registries in the USA and Europe have shown signs of stabilization and sometimes falling incidence rates  [4] [5] [6] [7]. In other large-scale KRT registries like in Australia and New Zealand [8] and Canada  [9] , the increase in incidence rates also slowed down after the 1990s. Nevertheless, KRT prevalence continued to rise worldwide  [2]  and patient survival continued to improve in many parts of the world  [4, 9, 10]. The aim of this study was to examine the trends in the incidence and prevalence of patients on KRT for end-stage kidney disease (ESKD) across European countries from 2008 to 2017, and secondly, it reports the trends in patient and graft survival comparing the 2008-10 and 2011-13 patient cohorts using data from the ERA Registry.
Compliance with ethical standards was confirmed by the medical ethical committee of the Amsterdam Medical Centre (W21_123 No. 21. 136). In the ERA Registry, data quality is controlled by manual and automated data checks using standardized (data-handling) protocols and close correspondence on data interpretation with participating KRT registries. To account for delayed reporting, the period 2008-17 was selected in the 2018 database. Only in case of the UK, the 2017 database was used, therefore delayed reporting could not be taken into account and the maximum survival follow-up was set at 31 December 2017. Data on children were unavailable for the renal registries of Dutch-and French-speaking Belgium; the Spanish regions of Cantabria, Castile and Léon, and Castile-La Mancha; and the UK including England, Northern Ireland and Wales.
The exclusion of data on children from these registries will result in an underestimation of approximately 2 prevalence per million population (pmp) for incidence and 13 pmp for prevalence in these regions, but this will not influence trends. Data were complete except for primary renal disease (PRD), for which we used a category 'missing'. Details on data collection and processing methods have been published in the ERA Registry annual reports (available on https://www. era-online. org/en/registry/).
Incidence and prevalence Incident counts were defined as the number of patients starting KRT (any form of dialysis or pre-emptive kidney transplantation) during a year and prevalent counts as the number of patients who were alive and receiving KRT (any form of dialysis or kidney transplantation) on December 31 of a year. The crude incidence and prevalence pmp were calculated by dividing the number of patients by the midyear general population of the country or region, multiplied by one million. In case the percentage coverage of the general population by the renal registry was <100%, we corrected for this by adjusting the general population data with the lower coverage. Standardized incidence and prevalence pmp were determined using the age and sex distribution of a reference population (i.
e. the EU28 population in 2015)  [12]. Incidence pmp will be further indicated as incidence and prevalence pmp as prevalence. Analyses were stratified by age group, sex and PRD, with the latter being classified according to the ERA coding system  [4]. Where the incidence or prevalence was calculated by age group, this was done by dividing the number of patients in a particular age group by the general population in that age group, resulting in an incidence or a prevalence per million age-related population (pmarp). Population data were obtained from the statistical office of the European Union (Eurostat)  [12]  or the national statistics agency in each country.
R statistical software 4. 0. 4 (R Foundation for Statistical Computation, Vienna), including the packages dplyr (version 1. 0. 5), survival (version 3. 2. 7) and survminer (version 0. 4. 9), was used for the calculation of incidence, prevalence and survival  [14] , whereas the Joinpoint Regression Program was used for trend analyses  [15].
Incidence Previous studies from the ERA Registry have shown that the overall standardized incidence of KRT in Europe increased substantially from 1990 to 2000  [5, 6] , flattened from 2000 to 2008  [4, 5]  and declined from 2008 until 2011  [4]. In the current ERA Registry study, we found a similar decline for this latter period , although it was not statistically significant, and was therefore referred to as a stable incidence. A secondary analysis of our dataset showed that this difference between studies was mainly due to a different selection of countries. The incidence was stable between 2008 and 2011, but thereafter we found that the incidence slightly increased from 2011 to 2017. Also in the USA, there was a considerable increase in the 1990s followed by a stabilization, whereas no increase in the standardized incidence was seen from 2011 to 2017  [7].
Therefore, high kidney transplant rates should remain a priority, even if this means a further increase in the prevalence of KRT. This study has several strengths and limitations. We included data from a very large patient cohort assembled from multiple European national and regional KRT registries representing countries in Northern, Western and Southern Europe that have provided individual patient data for many years. Extensive data quality control was conducted to ensure optimal quality. Still, the interpretation and assignment of PRD coding might vary between participating KRT registries  [62]. Data on race and ethnicity and comorbidities are not available for all countries in the ERA Registry. We were however able to adjust for age and primary renal disease, which accounts for a large part of the confounding effect of comorbidity  [63].
ACKNOWLED GEMENT S We would like to thank the patients and the staff of the dialysis and transplant units for contributing the data via their national and regional renal registries. Furthermore, we gratefully acknowledge the following registries and persons for their contribution of the data:  Austrian Dialysis and Transplant Registry (OEDTR)  (F. Engler,  R. Kramar ,  G. Mayer  and the  Austrian Society of Nephrology) ;  Dutch speaking Belgian Society of Nephrology (NBVN)  ( M. Couttenye  and  F. Schroven );  French speaking Belgian Society of Nephrology (GNFB)  (J. M. des Grottes);  Renal Registry Danish Nephrology Registry (DNS)  ( K. Hommel );  Finnish Registry for Kidney Diseases  ( P. Finne  and  H. Niemelä ); France: The  Epidemiology and Information Network in Nephrology (REIN)  (C.
METHODS Data originated from routine surveillance, collected daily in a centralized electronic database for 228 nursing homes in France (97), Belgium (73), Spain (45), and Italy (13) between March 13 th , 2020, and February 20 th , 2021. Data collection complied with the European General Data Protection Regulation (GDPR). We compared the incidence of cases in time with that in the general population in each country. We defined an "episode of introduction" in a nursing home as a time period during which COVID-19 cases were detected in residents or staff with less than 14 days intervals between successive cases  [18]. We computed the attack rate during an episode and determined whether the initial case of an episode was a resident and/or a staff member. We computed the percentage of successful introductions (episodes leading to at least one case).
Design and participants This survey is nested in the French CONSTANCES population-based cohort  8  which includes approximately 200,000 adults aged 18 to 69 at inception. Since 2012, participants have been selected from the French adult population affiliated with the National Fund for Health Insurance according to a random sampling scheme stratified for age, gender, socioeconomic status and region of France to be representative of the source population, and have been followed by repeated yearly questionnaires and linked by administrative databases. CONSTANCES is also one of the three adult cohorts that is involved in the SAPRIS-SERO ("Santé, Pratiques, Relations et Inégalités Sociales en population générale pendant la crise COVID-19" -Serology) survey, whose aim is to quantify the cumulative incidence of SARS-CoV-2 infection in the French population using the dried blood spot (DBS) test for anti-SARS-CoV-2 antibodies.
Multivariable OR estimates were adjusted for sex, age, educational level, comorbidities lasting more than 6 months and the number of symptoms reported during the first wave of the pandemic (aOR). Indeed, persistent symptoms seem to be epidemiologically associated with the number of acute symptoms in hospitalized patients and in outpatients with COVID-19. 11, 12 All tests were two-sided and P< 0. 05 was considered statistically significant. We also used longitudinal data for the 10 symptoms that were collected in all questionnaires to compare the persistence of each of these symptoms between Sero-and Sero+ participants. We finally conducted a mediation analysis for all persistent symptoms associated with the serological status in univariable analysis. In this analysis, we assumed that a part of the association of the serological status on persistent symptoms was mediated by the acute symptoms caused by the infection; in other words, the acute symptoms are supposed to be in the causal pathway between the infection and the persistent symptoms and cannot be considered as a confounding factor (figure  1 ).
A first logistic model predicted the probability of persistent symptom according to serological status, ECDC status, an interaction term between these two covariates, and the confounding factors. The second model predicted the probability of ECDC status according to serological status and the confounding factors. Direct and indirect aOR estimates were deduced from these two logistic models (formulas can be found in ref 16). All the mediation models were adjusted on age, sex, and comorbidities. Confidence intervals for estimates were calculated using bootstrap with 10 000 replicates. Statistical analyses were performed using R software 4. 0. 5. Mediation analysis was performed using the CAUSALMED procedure in SAS 9. 4.
SARS-CoV-2 infection was evaluated by serological tests in all individuals. Data were not collected through the healthcare system, making the reported symptoms more representative of those perceived by the general population than in previous studies using healthcare databases. 18, 26 s work has certain limitations. First, symptoms were self-declared and were not evaluated with specific scales. Also the declarations may have differed depending on the recent medical history, especially during the pandemic where participants were more apt to believe that they had had COVID-19. 22 In addition, we could not separate persistent symptoms related to an infection (COVID-19 or other) from those related to otherwise poor health or a change in access to health care. Moreover, the possibility of serology misclassifications cannot be excluded.
Funding The Constances cohort benefits from a grant from the  French National Research Agency  [Grant Number  ANR-11-INBS-0002 ]: It is supported by the  Caisse Nationale d'Assurance Maladie (CNAM) , the  French Ministry of Health , the  Ministry of Research , the  Institut national de la santé et de la recherche médicale. CONSTANCES and is also partly funded by  MSD ,  AstraZeneca ,  Lundbeck and L'Oreal. The  SAPRIS-SERO study  was supported by  Agence Nationale de la Recherche , # ANR-10-COHO-06 , Santé Publique France :  N°20DMIA014-0 ,  Fondation pour la Recherche Médicale  (# 20RR052-00 ),  Inserm  ( Institut National de la Santé et de la Recherche Médicale ), # C20-26.
Electrocardiogram Measurements. Heart rate (in BPM) was measured with an ECG, using 3 electrodes placed on the thorax. The BIOPAC MP150 (System Inc, Santa Barbara, CA) software was used for the acquisition of the signal. The ECG signal was sampled at 1000 Hz and recorded using the AcqKnowledge software (BIOPAC System Inc, Santa Barbara, CA). The mean heart rate during each MATB-II variant was computed with the Kubios® software.
Statistical Analysis Behavioral performance was processed using a homebuild python script and all data was analyzed with R statistical software. As the data was not normally distributed, in particular subjective evaluations, we used the Wilcoxon signed-rank test to compare the conditions. Regarding performances comparisons across the three MATB-II variants, we focused the analysis on the COMM and RESMAN subtasks. We also conducted correlation and linear regression analyses using the performance measures of each task (MATB-II and neuropsychological tasks). For these correlations, we used TRACK, RESMAN, and COMM subtasks. SYSMON performance was not used to reduce the number of variables.
Comprehensive genetic studies have scripted the mutational landscape of MDS/MPN. These genetic alterations further refine prognosis, including chromosomal abnormalities  [28] [29] [30]  and gene mutations  [22, [31] [32] [33]. The latter have recently been included in three distinct prognostic scoring systems  [31] [32] [33]. Mutations in ASXL1 are included in all three, whereas the molecular CMMLspecific prognostic scoring system (CPSS-mol) also includes mutations in SETBP1, NRAS, and RUNX1  [31]. A recent study on behalf of the MDS/MPN IWG has validated several prognostic models illustrating comparable performance though significant heterogeneity in prediction outcomes exist among them  [34]. These shortcomings could be circumvented by the development of personalized predictions using machine learning on large knowledge databases  [35].
Access to DNMTi therapy for these patients is also (variably) restricted across different healthcare systems. For patients with proliferative CMML, hydroxyurea was more effective and achieved responses faster than cytotoxic chemotherapy with etoposide  [8]. Despite this, responses were not complete, and prognosis remained poor. A recently published large (n = 949) retrospective cohort study of CMML patients in Austria, patients with higher-risk CMML (myeloproliferative CMML, blasts ≥ 10%, CMML-1/2, or higher-risk CPSS)  [51]  had significantly improved survival with DNMTi treatment (n = 551) versus other treatments (n = 398; 20. 5 months [95% CI 18. 5-23. 5] vs 14. 3 months [12. 2-16. 1]; p < 0. 0001). However, the European multicenter randomized phase III DACOTA trial evaluating decitabine ± hydroxyurea versus hydroxyurea in advanced proliferative CMML (NCT02214407) revealed no difference in outcomes  [52].
Key discoveries and unanswered questions In 2013 and 2014 a consortium of clinical and laboratory experts in MDS/MPN convened in 3 congresses to address topical issues. Culminating from those meetings was the publication of proposed uniform response criteria for MDS/MPN  [74]. Until that time, MDS/ MPN patients were either excluded from clinical trials or responses were variably determined using criteria developed for other myeloid diseases. The development of uniform response criteria specifically for MDS/MPN would assist with application and translation of clinical trial results of MDS/MPN patients in the real-world setting. Since the first meetings, the MDS/MPN IWG has expanded to include clinicians and researchers at more than 60 institutions across the United States and Europe. The MDS/MPN IWG meets regularly to review evolving data that influences both our understanding of the pathophysiology of MDS/MPN diseases and our approach to treatments.
Novel agents under investigation in ABNL MARRO-001 The ABNL-MARRO 001 study (NCT04061421) endeavors to evaluate the safety and efficacy of oral combination therapies in MDS/MPN patients. DNMTi such as azacitidine and decitabine inhibit DNA methylation and allow previously silenced genes to be expressed and to exert direct cytotoxic effects on abnormal hematopoietic cells in the bone marrow. Although responses to single agent DNMTi are limited, DNMTi have been employed in various myeloid diseases where more effective treatment options are lacking, including in CMML, in MDS, and in elderly/unfit patients with AML  [46, [88] [89] [90]. The administration of azacitidine or decitabine is cumbersome for patients, as they are administered daily by subcutaneous or intravenous routes for 5-7 consecutive days each 4-week cycle until disease progression.
Study oversight and guidance Multiple committees and subcommittees have been organized for the development, oversight, and management of AM-001 and for analysis of AM-001 study data. The Protocol Development Committee has drafted and refined the protocol based on input of all other committee members and will continue to refine the protocol if amendments are needed. The Patient-Reported Outcomes (PRO) and Symptom Assessment Committee advises on the collection, use and analysis of data collected directly from the study subjects regarding their personal study experience (including but not limited to symptom scores and quality of life metrics). The Correlative Science and Biospecimen Committee oversees the collection and utilization of biological specimens collected from each subject in conjunction with AM-001.
Prognostic indices A "global" MDS/MPN prognostic index that has been validated across MDS/MPN subtypes and that informs treatment in MDS/MPN remains elusive. Demographic, clinical and pathologic data will be collected from subjects enrolled in AM-001 to test the applicability of available prognostic indices across MDS/MPN subtypes. Molecular data will also be collected to explore the impact of emerging genetic risk factors in these rare and heterogeneous diseases that may not have been incorporated into indices that were developed prior to widespread use of genomic analysis.