dataesr/scientific-paragraphs-categorization huggingface dataset:
Study population A total of 20 cardiac transplant patients were included providing 31 comparisons CMR-EMB. All EMBs were performed within 1 year of transplantation, all CMR were performed within 24 h of EMB. Table  1  summarizes the clinical, CMR and biopsy characteristics of the population. The median age of our population was 58 [49-64] years and the median LV ejection fraction was 63 [54-65] %. A total of 7 EMBs were positive for rejection including 6 cellular rejections and 1 AMR rejection. Cellular rejections ≥ grade 1R were specifically treated. All acute cellular rejections occurred within 6 months of transplantation. Table  2  summarizes heart rate at the time of mapping acquisition and data on LV and RV parameters in the 2 groups (rejection and no rejection). No differences were significant.
Study limitations Our study is limited by its small sample size. We therefore were not able to compare patients with cellular rejection to patients with AMR. With only one patient with a control CMR 3 months after the initial episode, we were not able to assess CMR as a useful tool for the response to therapy. CMR was performed close to routine EMB but not always the day of the biopsy. However, CMR was always performed before acute rejection therapy. CMR was performed preferentially in patients who had a suspected rejection on the basis of results from clinical and echocardiography data which precludes the generalization of our findings. We do not think that this selection of patients might have had an important impact on our results.
Acknowledgments This work was supported by a grant from the  Bill & Melinda Gates Foundation  ( OPP1150674 ). KSR gratefully acknowledges funding of the NTD Modelling Consortium by the  Bill & Melinda Gates Foundation  in partnership with the  Task Force for Global Health  under grant number  OPP1053230. AML, BB, EM, GS, HI, MK, VJ, and VL are supported by  TrypanoGen  funded by the  Wellcome Trust  (grant number  099310/Z/12/Z ). NC acknowledges funding from the  Bill & Melinda Gates Foundation  under grant  OPP1156227. LMF is funded by  Fundacao para a Ciencia e Tecnologia  ( IF/01050/2014 ). FAO contribution to this study was provided in the framework of the  Programme against African Trypanosomosis (PAAT) , and supported by the  Government of Italy  ( FAO Project  ' Improving food security in sub-Saharan Africa  by supporting the progressive reduction of tsetse-transmitted trypanosomosis in the framework of the NEPAD', codes  GTFS/RAF/474/ITA  and  GCP/RAF/502/ITA ).
| Efficacy Efficacy data are presented in Table  4. Among the 60 paediatric patients who participated in the two studies, a total of 954 bleeding episodes were reported (804 in the PTP study, 150 in the PUP study). No incidents of LETE were reported for on-demand treatment of these bleeding episodes. In the prophylaxis setting, following a total of 4209 infusions (2457 in the PTP study, 1752 in the PUP study), a total of 4 incidents of LETE (2 from each study) were reported. Using the 4point scale, 92. 9% (97. 8% in the PTP study, 66. 4% in the PUP study) of first infusions for on-demand treatment of a bleeding episode were rated as "excellent" or "good. " Overall, 93. 6% (94. 7% in the PTP study, 88. 0% in the PUP study) of bleeding episodes resolved with a single on-demand infusion of moroctocog alfa (AF-CC).
ACKNOwLeDgMeNTS The authors thank  Françoise Dromer , for providing the picture of the whole brain of infected mouse. The authors also credit the histopathology and models unit at the  Institute Pasteur, Paris. AC was supported by grants  5R01HL059842 ,  5R01AI033774 ,  5R37AI033142 , and  5R01AI052733. AA was supported by a  Fullbright and monahan fellowship  and a grant from the  Philippe Foundation.
AbstrACt Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level).
Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes.
The HELIX project aims to measure and describe multiple environmental exposures from the different exposome domains during early life (pregnancy and childhood) and associate these with omics markers and child health outcomes. The background, rationale and detailed objectives of the HELIX project have been described elsewhere at the start of the project. 3 HELIX takes early life as a key starting point for defining the exposome because, as recognised in the Developmental Origins of Health and Disease research, it is well recognised that the periods of organ development during prenatal life and infancy are especially vulnerable to the effects of environmental risk factors, which may manifest themselves throughout the lifetime in adult diseases. 4 Essential to exposome research is the collection of data on many environmental exposures from the different exposome domains in the same subjects.
Cohorts PArtICIPAtIng In hELIX The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in Europe: the Born in Bradford (BiB) study in the UK,  5  the Étude des Déterminants pré et postnatals du développement et de la santé de l'Enfant (EDEN) study in France,  6  the INfancia y Medio Ambiente (INMA) cohort in Spain,  7  the Kaunus cohort (KANC) in Lithuania,  8  the Norwegian Mother and Child Cohort Study (MoBa)  9  and the RHEA Mother Child Cohort study in Crete, Greece 10 (table  1 ). These cohorts were selected for participation in the HELIX project because: (a) they could provide substantial existing longitudinal data from early pregnancy through childhood, (b) they could follow-up children at similar ages, (c) they could integrate questionnaires, Open access biosampling and clinical examinations using common HELIX protocols and (d) they offered heterogeneity in terms of exposure and population characteristics.
Pregnant women in the original cohorts were recruited between 1999 and 2010. Three cohorts (INMA, KANC, RHEA) recruited during the first trimester of pregnancy, two through the first and second trimesters (EDEN, MoBa), while in the BiB cohort women were recruited between weeks 26 and 28 of gestation (second/third trimesters). Inclusion and exclusion criteria varied between cohorts, as described in table 1. All cohorts included at least one follow-up point during pregnancy, one at birth and several after delivery. Based on these six existing cohorts, HELIX used a multilevel study design, drawing on nested study populations for data collection of different intensities (figure  1 ): (1) the entire cohort in which factors arising primarily from outdoor exposures were assessed through geospatial models and linked to existing health outcome data; (2) a subcohort in which one new follow-up examination of the children between ages 6 and 11 years was carried out in order to assess child health outcomes and to fully characterise different areas of the exposome through questionnaires, biological sample collection and biomarker and omics measurements and (3) two panel studies in children and pregnant women to characterise in depth the variability in exposure biomarkers and omics biomarkers, individual exposure-related behaviours and personal exposures.
Open access hELIX EntIrE Cohort The study population for the entire HELIX cohort includes 31 472 women who had singleton deliveries between 1999 and 2010, and for whom exposure to ambient air pollution during pregnancy had been estimated as part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. 11 The entire cohort includes nine regions from the six cohorts; we included only regions where geographic data were available to calculate air pollution levels and built environment indicators (table  1 ). This meant, for example, that the city of Oslo and not the whole of the national MoBa cohort was included, and that only the Gipuzkoa, Sabadell and Valencia regions of the INMA study were included. In the other cohorts, women residing outside the main urban areas were excluded for the same reason.
In this study population, data on many variables had been collected in the individual cohorts during previous data collection points (during pregnancy and between birth and 5 years of age). Existing data included information on certain exposures (eg, maternal tobacco smoking during pregnancy, environmental tobacco smoke), key covariates (eg, pregnancy complications, maternal and child diet, maternal and child physical activity, child sleep, breast feeding, other health-related behaviours, indicators of socioeconomic status) and health and development outcomes. As part of HELIX, relevant datasets from all 31 472 mother-child pairs were transferred from the six cohorts to the central HELIX data warehouse located at the Barcelona Institute for Global Health (ISGlobal) (see below). Through data harmonisation, these cohort-specific variables were converted to harmonised variables.
hELIX subCohort From the entire cohort, a subcohort of mother-child pairs was selected to be fully characterised for a broad Eligibility criteria for inclusion in the subcohort were: (a) age 6-11 years at the time of the visit, with a preference for ages 7-9 years if possible; (b) sufficient stored pregnancy blood and urine samples available for analysis of prenatal exposure biomarkers; (c) complete address history available from first to last follow-up point; (d) no serious health problems that may affect the performance of the clinical testing or impact the volunteer's safety (eg, acute respiratory infection). In addition, the selection considered whether data on important covariates (diet, socioeconomic factors) were available. Each cohort selected participants at random from the eligible pool in the entire cohort and invited them to participate in this subcohort until the required number of participants was reached.
In total, 1301 mother-child pairs with complete questionnaire and clinical examination data, and urine and blood samples, were included in the HELIX subcohort (figure  1 ). Several cohorts then invited and examined further subjects (n=322) following the same protocols for clinical examination and sample collection, and the same questionnaires, but these were not included in the measurement of exposure biomarkers for the HELIX study (figure  1 ). Among the 322 extra individuals, 266 came from INMA-Sabadell, 26 from BiB, 7 from EDEN, 3 from KANC, 19 from MoBa and 1 from RHEA. For some of these individuals omics data were collected. These individuals may be included in studies with another focus than exposure biomarkers, which is why they are shown in figure  1. The new follow-up visits for the subcohort took place in the six study centres at a local hospital, a primary care centre or at the National Institute for Public Health (NIPH) in Oslo.
Questions on exposures during the day and week before the visit were asked separately in a short questionnaire and repeated during the second period of nested child panel study (see below). Additionally, questions related to addresses, places visited and travel were collected using a custom-made Google mapsaided commuting questionnaire based on the free Geographic Intelligent Software (GIS), qGIS software  16  that allowed mothers to trace their child's commuting routes directly on the computer. This information was used to enhance the accuracy of location data collected through the main questionnaires and integrated with the outdoor exposure estimates to provide exposure estimates at different locations and for different time-activity patterns (eg, home, school, commuting exposures). A total of 98.
Anthropometry and body composition During the subcohort follow-up examination, anthropometric data were collected using regularly calibrated instruments: height was measured with a stadiometer and weight with a digital weight scale, both without shoes and with light clothing. Height and weight measurements were converted to body mass index (BMI in kg/m²) for age-and-sex z-scores using the international WHO reference curves in order to allow comparison with other studies. 17 Overweight and obese children were defined as those above the age-andsex-specific 85th and 95th percentiles, respectively, as recommended by WHO (http://www. who. int/ mediacentre/ factsheets/ fs311/ en/). Circumferences (arm, waist, head) were measured with a metric tape and recorded in duplicate. Four skinfolds were measured (triceps, subscapular, suprailiac, thigh), following the protocols as described in the report from National Health and Nutrition Examination Survey III Body Measurements (anthropometry).
Data from existing regulatory monitors were used to back extrapolate ambient air pollution exposure models. The estimates for these outdoor exposures were calculated for the prenatal period and several postnatal periods up to the HELIX subcohort follow-up time point (table  3 ). Furthermore, in the subcohort, biomarkers of contaminant exposure were measured in appropriate biological samples collected from the children at age 6-11 years and in samples previously collected from mothers during pregnancy or from the neonates during delivery (cord blood) and stored in cohort biobanks (table  3 ). Chemical assays were conducted in the laboratory at the Department of Environmental Exposure and Epidemiology at the NIPH, apart from analyses of metals/elements and cotinine, creatinine and blood lipids, which were subcontracted to ALS Laboratory Group Norway AS and Dr Fürst Medisinsk Laboratorium AS, respectively.
Specific procedures are in place within HELIX to safeguard the privacy of study subjects and confidentiality of data. First, any reported study results pertain to analyses of aggregate data; no variables or combination of variables that can identify an individual will be associated with any published or unpublished report of this study. Primary databases with personal information (such as geocodes, dates, questionnaires or health outcomes) have been stored on separate computers with personal identifiers removed. Subjects are identified by a unique study number, linking all basic data required for the study. The master key file linking the study numbers with personal identifiers is maintained in each cohort. For the dataset analysis, all information that enables identification of an individual (dates, geocodes, etc) is removed before distribution of datasets to the researchers.
dAtA wArEhousE Relevant datasets from all 31 472 mother-child pairs were transferred from the six cohorts to the central HELIX data warehouse located at ISGlobal. The HELIX data warehouse consists of several schemas, which are linked by means of common identifiers in a relational database created in MySQL. 44 New data, collected through the common protocols during the subcohort and panel study fieldwork, were entered directly into an electronic database and then uploaded into the data warehouse. Questionnaires were computer-based with a direct entry to the database. All data were locally and centrally checked by examination of the ranges, distributions, means, SD, outliers and logical checks. Data outliers and missing values were checked with the local cohort field workers and, where possible and relevant, replaced by correct values.
Acknowledgements The authors would like to thank all the participating children, parents, practitioners and researchers in the six countries who took part in this study. The authors would like to thank  Sonia Brishoual ,  Angelique Serre  and  Michele Grosdenier  ( Poitiers Biobank ,  CRB BB-0033-00068 , Poitiers, France) for biological sample management and  Professor Frederic Millot  (Principal Investigator), Elodie authors read and approved the final manuscript. ISGlobal is a member of the Agency for the  Research Centres of Catalonia (CERCA) Programme ,  Generalitat de Catalunya. MC is a member of the  MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK. ISGlobal is a member of the Agency for the  Research Centres of Catalonia (CERCA) Programme ,  Generalitat de Catalunya.
MC is a member of the  MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK. Funding The research leading to these results has received funding from the  European Community 's  Seventh Framework Programme  ( FP7/2007-206 ) under grant agreement no 308333-the  HELIX  project. Dr Maribel Casas  and  Dr Jordi Julvez  received funding from  Instituto de Salud Carlos III (Ministry of Economy and Competitiveness)  ( MS16/00128 ,  MS14/00108 ). INMA data collections were supported by grants from the  Instituto de Salud Carlos III, CIBERESP , the  Conselleria de Sanitat, Generalitat Valenciana, Department of Health of the Basque Government ; the  Provincial Government of Gipuzkoa , and the  Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the  Lithuanian Agency for Science Innovation and Technology  ( 6-04-2014_31V-66 ).
The search strategy was based on the STN databases, starting from the CAS numbers (including the different salts of MAA) and interrogated for the different toxicological endpoints including metabolism and toxicokinetics. This paper proposes a category approach for the toxicological assessment of short chain methacrylate esters to fill in data gaps by readacross. Estimates for repeated dose toxicity are derived for the group members with no experimental data to satisfy information requirements of the EU REACH regulation. The scenarios described by  ECHA (2015 ECHA ( , 2017a) )  have been used to describe the mechanisms relevant for the different endpoints. The scheme proposed by  Blackburn and Stuard (2014)  is applied to define the level of uncertainty of each read-across (cf. electronic supplement).
In addition, a minor contribution due to rapid ester hydrolysis cannot be excluded for systemic toxicity at high doses or after inhalation when first pass liver metabolism becomes incomplete. Again, scenario 3/5 will be most relevant and an estimate about the relative contribution in relation to scenario 4/6 at high doses is not possible. b. Local effects after ester cleavage leading to high intracellular cytotoxic concentrations of MAA, corresponding to scenario 3/5 and governed by AE 2 and 3 (biological target and its exposure to the common compound). This may in principle play a role for every exposure route depending on the exposure concentration, the rate of passage through, and the rate of metabolism within the local tissues. This scenario is most relevant for local effects on the nasal passages after inhalation and a robust database is available in this regard.
In any case a low dermal toxicity is apparent. The uncertainty of this readacross is low according to the scheme of  Blackburn and Stuard (2014)  based on the low acute dermal toxicity of MMA and n-BMA in conjunction with the low acute oral toxicity of all group members (cf. electronic supplement). 4. 1. 2. 3. Dermal irritation. Animal data are available for all members of the category. They are inconsistent reflecting differences between the protocols used, but the total database shows that the esters are slightly irritating to the skin of rabbits under semi-occlusive conditions for short durations, with moderate irritation under occlusion and prolonged contact. With this complete data set read-across is not necessary. 4. 1. 2. 4. Skin sensitization. Data are available for all members of the category so read-across is not required.
The sensitizing potential of MMA was investigated in a large number of guinea pig studies (cf. ECETOC, 1995)  and in the local lymph node assay (LLNA)  (Betts et al. , 2006). The total database showed that MMA is a weak skin sensitizer. EMA and 2-EHMA appeared to give equivocal results in adjuvant studies in guinea pigs. The only test with i-BMA was negative, while n-BMA was positive in a guideline maximization test. A series of LLNA studies in mice with different concentrations of EMA  (Dony, 2013a) , i-BMA  (Dony, 2013b) , n-BMA  (Dony, 2013c ) and 2-EHMA  (Dony, 2013d)  confirmed the low sensitizing potency of these group members. The concentration of the test material leading to a 3fold increase of cell proliferation induced nuclear labelling by [ 3 H] methyl thymidine in the local lymph nodes (EC 3 ) was taken as a quantitative indicator for the sensitizing potency.
(1993)  with n-BMA. As there appears to be no marked influence of exposure duration on NOAELs, the read-across to fill in data gaps may well encompass exposure durations up to 2 years and a conservative approach would certainly allow predictions up to 90 days. For oral exposure the systemic NOAELs for the three substances with experimental data (MMA, n-BMA and 2-EHMA) are in the range of 100-300 mg/kg/d. On a mMol/kg/d basis they are comparable taking into account all uncertainties surrounding numerical values of NOAELs noted above. The range is about 0. 5-1. 5 mMol/kg/d; the NOAEL of the OECD TG 422 study for n-BMA with shorter duration is slightly higher as is to be expected. By interpolation within the category it would be expected that EMA and i-BMA would also have comparable NOAELs in the range of 0.
5-1. 5 mMol/kg/d. The same can be assumed for MAA, the common metabolite. Estimates in mg/kg/d are then derived on the basis of the molecular weights for the category members with data gaps leading to ranges of interpolated NOAELs after oral exposure of 40-130 mg/kg/d for MAA, 60-170 for EMA and 70-200 for i-BMA. Systemic NOAELs for MAA and MMA after inhalation are 1. 1 mMol/ kg/d, in the same range as after oral exposure. This supports the notion that systemic effects at both exposure routes, oral and inhalation, are driven by MAA, the common systemic metabolite. But the NOAEL for n-BMA is clearly higher (11 mMol/kg/d), which may in the first place be explained by the shorter exposure duration and the limited parameters investigated in a 28 day study in comparison to the 90 day study with MAA and the 2 year study with MMA.