dataesr/scientific-paragraphs-categorization huggingface dataset:
Metabolites of DEHP and DEHT Primary and secondary metabolites of DEHP and DEHT were synthesized and characterized by the IMOST team (UMR 1240, INSERM) in Clermont-Ferrand, France. The compounds tested are shown Table  1. The purity of all our synthesized metabolites and their corresponding intermediates exceeded 95% (HPLC/MS and RMN). MEHT was synthesized according to the method described par Eljezi et al. (Eljezi et al. 2017). All synthesis processes are described in the supplementary data (appendix 1). et al. , 2005; Eljezi et al. , 2017) , respectively (Scheme 1). Derivatives (4) and (7) were obtained by Wacker oxidation of the vinylic group at -position of compound (3) in a mixture of PdCl 2 and parabenzoquinone or a hydroboration reaction, respectively. Compound (4) was then converted into 5-oxo-MEHT (5) by hydrogenation, with the ketone group then being reduced with NaBH 4 to form 5-OH-MEHT (6).
Statistical analysis Obtained data were statistically analyzed using the PC program GraphPad Prism 6. 00 (GraphPad Software Incorporated, San Diego, CA, USA). Descriptive statistical characteristics (arithmetic mean, minimum, maximum, standard deviation and coefficient of variation) were evaluated. One-way analysis of variance (ANOVA) and the Dunnett´s multiple comparison test were used for statistical evaluations. The level of significance was set at ***P < 0. 001; **P < 0. 01 and *P < 0. 05.
Docking Metabolites of DEHP and DEHT were docked into TRα1, the only TRα subtype to bind T3, and TRβ1, the only β subtype crystallized. The coordinates of the receptor subtypes were taken from the RCSB ProteinDatabank under the entry 4lnw  (Souza et al. , 2014)  crystallized with T3, and 1n46  (Dow et al. , 2003) , bound to an agonist, respectively. The ligands were extracted manually and both molecules were assigned using the Gasteiger-Hückel method. The ligands were subjected to an energy minimization using the maximin2 protocol of the Sybyl 6. 9. 1 molecular modeling package. The co-crystallized T3 was cross-docked with very good precision, indicating that the docking protocol was sound. It consisted of a 30-solution GOLD run in a binding site defined as a sphere of 10 Å around the co-crystallized ligand with 100,000 operations and the ChemPLP scoring function.
, 2004). All in vitro and in vivo data suggested that DEHP is able to influence thyroid tissues at low doses. Though, studies on the in vitro effects of plasticizer metabolites on the TH system are scarce, it is well known that diesters are highly metabolized in vivo. Reduced serum thyroid hormone levels have been well documented in human populations, with higher urine phthalate metabolites in various regions around the globe  (Boas et al. , 2006; Gao et al. , 2017; Meeker et al. , 2007; Wu et al. , 2013). In this study, we observed that 5-OH-MEHP, in contrast to MEHP, also induced a decrease in the presence of T3 at the highest non-cytotoxic concentration, whereas below this concentration we saw a synergism at 5 µg/mL. In this assay, cell proliferation was measured as a consequence of T3 activation but the mechanism of cell proliferation is a complex biological phenomenon.
There is little biomonitoring data for DEHT in the literature, even less measuring the exposure of hospitalized newborns. Lessmann et al. studied the exposure of non-hospitalized children over 4 years of age to DEHT  (Lessmann et al. , 2017). However, only the oxidized metabolites of MEHT were measured in the urine. Pinguet et al. presented  results of the exposure of patients hospitalized in NICU to certain plasticizers, including DEHT  (Pinguet et al. , 2019). The median of the urinary concentrations of MEHT in this cohort of patients was lower than the limit of quantification (0. 018 ng/mL) and the maximum concentration measured was 9. 90 ng/mL, 200 times less than the concentration showing an antagonistic effect on T3 identified using the T screen assay in this study  (Pinguet et al. , 2019).
An evaluation of the comparative analysis of agronomic, phenotypic and compositional characteristics was carried out, and the safety of the newly expressed proteins and the whole food and feed were evaluated with respect to potential toxicity, allergenicity and nutritional characteristics. Environmental impacts and post-market environmental monitoring (PMEM) plan were also evaluated. The molecular characterisation data establish that the events stacked in maize NK603 9 T15 9 DAS-40278-9 have retained their integrity. Protein expression analysis showed that the levels of the newly expressed proteins are similar in the three-event stack maize and in the single events. The comparative analysis of agronomic and phenotypic characteristics and grain and forage composition identified no differences between maize NK603 9 T25 9 DAS-40278-9 and the non-GM comparator that required further assessment except for the change in plant lodging.
For these constituents (with the exception of erucic acid (C22:1), for which all the data were < LOQ), the Fisher exact test was applied in order to identify differences in the number of data points < LOQ; no statistically significant outcomes were identified. 18 Moisture, crude protein, crude fat, crude fibre, acid detergent fibre (ADF), neutral detergent fibre (NDF), ash, carbohydrates (by calculation), calcium and phosphorus. 19 Moisture, crude protein, crude fat, crude fibre, acid detergent fibre (ADF), neutral detergent fibre (NDF), total dietary fibre, ash, carbohydrates (by calculation), lauric acid (C12:0), palmitic acid (C16:0), palmitoleic acid (C16:1), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), a-linolenic acid (C18:3), arachidic acid (C20:0), eicosenoic acid (C20:1), behenic acid (C22:0), lignoceric acid (C24:0), alanine, arginine, aspartic acid, cystine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, calcium, copper, iron, phosphorus, potassium, sodium, magnesium, manganese, zinc, b-carotene, thiamin, niacin, pantothenic acid, pyridoxine, folic acid, atocopherol, c-tocopherol, total tocopherols (by calculation), p-coumaric acid, ferulic acid, inositol, phytic acid, raffinose and trypsin inhibitor.
Dietary exposure assessment to new constituents In line with Regulation (EU) No 503/2013, the applicant provided dietary exposure estimates to CP4 EPSPS, PAT and AAD-1 proteins newly expressed in NK603 9 T25 9 DAS-40278-9 maize. Dietary exposure was estimated based on protein expression levels reported in this application for the threeevent stack maize treated with the intended herbicides, the current available consumption data and feed practices, the foods and feeds currently available in the market and the described processing conditions. For the purpose of estimating dietary exposure, the levels of newly expressed proteins in NK603 9 T25 9 DAS-40278-9 maize grains, forage and pollen were derived from replicated field trials (four replicates from six locations) in 2018 in the United States and Canada (see Section 3.
Human dietary exposure Chronic and acute dietary exposure to CP4 EPSPS, PAT and AAD-1 proteins newly expressed in NK603 9 T25 9 DAS-40278-9 maize was provided. The applicant followed the methodology described in the EFSA Statement 'Human dietary exposure assessment to newly expressed protein in GM foods' (EFSA, 2019a) to estimate human dietary exposure in average and high consumers making use of summary statistics of consumption. Human dietary exposure was estimated across different European countries on different population groups: young population (infants, toddlers, 'other children'), adolescents, adult population (adults, elderly and very elderly) and special populations (pregnant and lactating women). Since no specific consumption data were available on commodities containing, consisting of or obtained from NK603 9 T25 9 DAS-40278-9 maize grains, a conservative scenario with 100% replacement of conventional maize by the GM maize was considered.
Consumption figures for all relevant commodities (e. g. corn flakes, sweet corn, popcorn, etc. ) were retrieved from the EFSA Comprehensive European Food Consumption Database (EFSA consumption database). 25 Corn oil was excluded from the assessment since no proteins are expected to be present in the oil. Mean protein expression values on fresh weight basis are considered as the most adequate to estimate human dietary exposure (both acute and chronic) when working with raw primary commodities that are commonly consumed as processed blended commodities (EFSA, 2019a). Different recipes and factors were considered to estimate the amount of maize in the consumed commodities before assigning newly expressed protein levels to the relevant commodities. 26 No losses in the newly expressed proteins during processing were considered, except for certain commodities excluded from the exposure estimations (maize oil, corn starch, corn syrup).
22 lg/g). Half the LOQ value was assigned to the left-censored data to calculate the mean. Mean levels (dry weight) of the newly expressed proteins in grains and forage from the three-event stack maize treated with the intended herbicide used for animal dietary exposure are listed in Table  7. The applicant estimated dietary exposure to CP4 EPSPS, PAT and AAD-1 proteins in livestock (i. e. poultry, swine, cattle and sheep), based on estimates for body weights, daily feed intakes and inclusion rates (percentage) of maize grains and forage in diets/rations  (OECD, 2013). Estimated dietary exposure in livestock animals was calculated based on the consumption of maize grain and forage alone or in combination, as reported in Appendix D.
C. 2. Statistical analysis of the 90-day study on DAS 40278-9 in rats The following endpoints were statistically analysed: body weight, body weight gain, feed consumption and feed efficiency, forelimb and hindlimb strength, motor activity data, sensory evaluation data, rectal temperature, haematology, coagulation, urinalysis and clinical chemistry values, absolute and relative organ weights. For all continuous endpoints, mean and standard deviation were provided for each dose group for each sex, variable and period or time interval. In the statistical analysis, rats consuming the low-and high-dose test diets were compared with those consuming the control diet. For continuous parameters, a linear mixed model was applied to data for individual animals for the two sexes combined (fixed effects: diet, sex and sex-by-diet interaction; random effects: block-within-sex and cage).
7 ). (3) Upward increase in the content of Na, K, Rb, Li, Mo, Cd, B, Ni, V, Cu, Ba, Co, U, and Sr (Fig. 7 ). Although the patterns of increase of the concentrations of these elements differ in details the general trend of their vertical distribution is upward increase. We do not have data for the vertical distribution of dissolved O 2 concentration along the sediment core NODKGS65. Therefore, in our interpretations of the vertical distribution of elements dissolved in the pore waters of core NODKGS65 we will use the dissolved O 2 profiles along the sediment core NODKGS63, which is close to NODKGS65 (Fig. 1 ). Dissolved O 2 J o u r n a l P r e -p r o o f Journal Pre-proof distribution along the sediment core NODKGS63 and close to a Mn-nodule shows abrupt downward decrease from 177 µmol/L in the bottom seawater to ~60 µmol/L at 1 cm depth and then gradual decrease to ~31.
In such a case, the heavy 66 Zn adsorbs more readily than the light 64 Zn due to preferential sorption of heavy Zn isotopes on Fe-Mnoxyhydroxides surfaces. Preferential adsorption of 66 Zn from the light Zn isotope pool (δ 66 Zn JMC < 0‰) of the pore waters (Zn aq is either free or inorganically-speciated) on the Mn-Feoxyhydroxides has resulted in heavy Zn-isotope composition of the Mn-micronodules (δ 66 Zn JMC = +0. 61 -+0. 90‰) and diagenetic layers of the Mn-nodules. In general, the chemical data for Mn-micronodules are scarce and it is not possible to give a meaningful estimation of their resource potential with such a limited database. The Mnmicronodules are poorer in most elements than the Mn-nodules and only Mn, Ni, Cu, Zn, and Mo are in concentrations higher than those in the Mn-nodules.
Acknowledgements The captain and crew of the  R/V L'Atalante  are thanked for their efforts to support the sampling and onboard sample treatment. Sincere thanks go to:  M. Ranneberg  for supporting the XRD analyses,  M. Hein  for the IR determinations, and  D. Henry  (all from  BGR ) for preparation of the polished block section. This research was supported by a  LabexMER Axis 3  (Geobiological interactions in extreme environments;  Institut Universitaire Européen de la Mer ,  Université de Bretagne Occidentale ) grant (project  NODESIS ) to V. M. Dekov.
Neuro-inflammation spanning the entire thickness of the retina. 7 Of particular interest is also the Henle Fibre outer nuclear layer (ONL) boundary of the parafovea where AQP4 channels are highly expressed. 8 0] [11] [12] [13]  Recent studies suggested potential astrocytopathy-related outer retinal layer (ORL) thinning in AQP4-IgG seropositive NMOSD but were limited in their sample size and in parts contradictory on the exact layers in which these changes occur. 8 11 It thereby remains unclear if ORLs, especially the ONL are also potentially affected by primary retinal astrocytopathy in AQP4-IgG seropositive NMOSD. Representing the largest international NMOSD dataset collected so far, the CROCTINO study (Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in Neuromyelitis Optica) overcomes one of the common weaknesses of NMOSD studies-being limited to small and homogenous sample populations.
Cohort design A total of 539 patients with NMOSD were recruited between 2000 and 2018 as part of CROCTINO (stratified data of centres by device type and number of patients are summarised in the online supplemental file 1). 14 Patients with (1) diseases potentially confounding OCT analyses (including glaucoma, diabetic retinopathy, retinal surgery and ametropia greater than ±6 diopters), (2) a history of ON within the last 6 months before baseline, (3) no evidence of seropositivity for AQP4-IgG or MOG-IgG  20 21  and (4) no macular OCT data were excluded. Cell-based assays were used for the detection of AQP4-IgG and MOG-IgG antibodies in serum samples from all patients. Clinical data (antibody serology, disease duration, frequency of ON, location of ON, date of ON, Expanded Disability Standard Scale and treatment received) were collected from all patients.
Neuro-inflammation APOSTEL V. 2. 0 recommendations. 24 Peripapillary retinal nerve fibre layer (pRNFL) thickness was derived using a device-specific protocol and centred around the optic nerve head. Segmentation of all layers in macular volume scans were performed semiautomatically and processed with an in-house proprietary software (SAMIRIX). 25 For the purposes of this study, the macular retinal layers were segmented in the following layers: macular retinal nerve fibre layer (mRNFL), ganglion cell and inner plexiform layer (GCIP), inner nuclear layer (INL), outer plexiform layer (OPL), ONL, the outer plexiform and nuclear layer (OPNL), photoreceptor layer (PR, inner photoreceptor segments to Bruch's membrane) and the total retinal thickness (RT, calculated as the thickness consisting of the RNFL (defined as layer no.
Statistical methods Data were stratified in cohorts by (1) antibody status and (2) ON history (contralateral eyes of patients with a history of unilateral ON are classified not fulfilling the ON history criteria). The data were further bifurcated by OCT device (Spectralis, Cirrus or Topcon) to mitigate any device-specific aberrations. For continuous cohort data (age, average age at onset and disease duration) on each of the AQP4-IgG, MOG-IgG and HC cohorts, the Student's t-test was employed. Cross-sectional group comparisons of the OCT values were conducted using linear mixedeffect models with age and sex as fixed and centre and patient-ID as random effects; where necessary, models were corrected for age and sex. Marginal and conditional coefficients of determination for the models were estimated by pseudo-R 2 for mixedeffect models.
30 31 Our AQP4-IgG seropositive cohort included an ethnically diverse dataset acquired worldwide with a lower African American patient composition (5. 6%), which might have contributed to the less profound foveal ONL changes. 11 32 ecently, it has been hypothesised that the neuroplastic characteristics of the INL may act as a barrier to retrograde (but not anterograde) trans-synaptic axonal degeneration-rectified to the ORLs-in patients with MS following ON. 33 This limited neuroplastic ability is hypothesised to rest with the bipolar, amacrine and horizontal cells, which feed into the synaptic tree at the level of the INL, and raises questions as to whether such protective mechanisms may also play a limited part in NMOSD and whether it remains so as we age. 33 The average age of participants in the two other studies were relatively older (mean age for both being 47 years), whereas for our AQP4-IgG cohort it was 42 years.
Acknowledges Partial funding by  Highly  specialised services NHS England. MIL reported being involved in aquaporin 4 testing, receiving salary from the  National Health Service National Highly Specialised Commissioning Group for Neuromyelitis Optica, UK , being supported by the  National Institute for Health Research Oxford Biomedical Research Centre, UK , and receiving speaking honoraria and travel grants from  Biogen Idec , and travel grant from  Novartis. SMS has nothing to disclose. AR-F is sponsored by  Abide Therapeutic  outside of the submitted work and reports no potential conflicts of interest. SSiritho received funding for travel and speaker honoraria from  Merck Serono, Pacific Healthcare (Thailand) ,  Menarini (Thailand) ,  Biogen Idec ,  UCB (Thailand) , and  Novartis. AA reports personal fees from received honoraria for giving educational presentations on multiple sclerosis and neuroimmunology at several national congresses or symposia from  Teva Turkey, Merck-Serono, Biogen Idec-Gen Pharma of Turkey, Roche ,  Novartis ,  Bayer ,  Sanofi-Genzyme.
She has received travel and registration coverage for attending several national and international congresses or symposia from  Merck-Serono, Biogen Idec-Gen Pharma of Turkey, Roche, Sanofi-Genzyme  and  Bayer. AJ has received compensation for advisory board, consulting, meeting attendance and speaking from  Biogen ,  Terumo-BCT ,  Genentech ,  Shire  and  Chugai Pharmaceuticals. SH has received funding from the  NMO Spectrum-UK  charity and was previously funded by an  MGA/Watney/NIHR Oxford Biomedical  research grant. RM serves on scientific advisory board for  MedImmune  and has received funding for travel and honoraria from  Biogen ,  Merck Serono ,  Novartis ,  Sanofi-Genzyme ,  Roche  and  Teva. EN has nothing to disclose. ACC received funding from the  Instituto de Salud Carlos III (Spain)   JR19/00007  unrelated to this manuscript.
DB has received speaking/ consulting honoraria from  Bayer Health Care, Biogen Idec ,  Merck ,  Sanofi-Genzyme , TEVA and  Roche  and had travel expenses to scientific meetings sponsored by  Bayer Health Care ,  Merck Serono, TEVA and Roche. JH reports grants for OCT research from the  Friedrich-Baur-Stiftung  and  Merck , personal fees and non-financial support from  Celgene ,  Merck ,  Alexion ,  Novartis ,  Roche ,  Santhera ,  Biogen ,  Heidelberg Engineering ,  Sanofi Genzyme and non-financial support of the Guthy-Jackson Charitable Foundation , all outside the submitted work. JH is partially funded by the  German Federal Ministry of Education and Research (DIFUTURE) , Grant Numbers  01ZZ1603 [A-D] and  01ZZ1804 [A-H]. LL received honoraria for consulting services from  Merck ,  Roche ,  Biogen  and for speaking activities from  Teva ; research support from  Merck ,  Biogen ,  Novartis ; travel support from  Merck ,  Roche ,  Biogen ,  Almirall.
MP has nothing to disclose. OA has received honoraria for speaking/consultation and travel grants from  Bayer Healthcare, Biogen Idec ,  Chugai ,  Novartis ,  Medimmune ,  Merck Serono , and  Teva  and research grants from  Bayer Healthcare, Biogen Idec ,  Novartis , and  Teva. MR received speaker honoraria from  Novartis ,  Bayer ,  Roche ,  Alexion  and  Ipsen  and travel reimbursement from  Bayer ,  Biogen ,  Merz ,  Genzyme ,  Teva ,  Roche  and  Merck , none related to this study. PA reports grants, personal fees and non-financial support from  Allergan ,  Biogen ,  Ipsen ,  Merz Pharmaceuticals ,  Novartis , and  Roche , personal fees and non-financial support from  Bayer Healthcare , and  Merck , and non-financial support from  Sanofi-Aventis/Genzyme. HJK reports speaking and/or consulting:  Bayer Schering Pharma, Biogen ,  Celltrion ,  Eisai ,  HanAll BioPharma ,  MedImmune ,  Merck Serono ,  Novartis ,  Sanofi Genzyme ,  Teva-Handok , and  UCB ; research support:  Ministry of Science & ICT, Sanofi Genzyme ,  Teva-Handok , and  UCB ; steering committee member: MedImmune; co-editor/associated editor: MS Journal-Experimental, Translational and Clinical; and  Journal of Clinical Neurology.
TJS was issued US patents covering the therapeutic targeting of IGF-I receptor in autoimmune diseases. He is a paid consultant for Horizon Thera and Immunovant and is a scientific advisor to the  Guthy-Jackson Charitable Foundation. He receives research funding from the  National Institutes of Health. AP is supported by the  National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London Institute of Ophthalmology. AB is cofounder and shareholder of Motognosis and Nocturne. He is named as inventor on several patent applications regarding MS serum biomarkers, OCT image analysis and perceptive visual computing. FP reports research grants and speaker honoraria from  Bayer ,  Teva ,  Genzyme ,  Merck ,  Novartis ,  MedImmune  and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work.
g. NCT02571725 and NCT03598270). Our findings, along with others showing an increased infiltration of CD8 + T cells after PARP inhibition,  10  support the hypothesis that PARP1 activity and immune infiltration are mechanistically linked, and provide a rationale for such combination therapies. To conclude, metabolic features of cancer cells, such as PDXK and PAR levels, can impact the immune infiltrate, thereby affecting the clinical course of LACC and NSCLC. Although the interplay between tumor metabolism, immune infiltrate and prognosis remains to be explored and the detailed mechanisms underlying these findings remain to be discovered, we believe that this area of research has the potential to elucidate new patient-relevant facets of the cancerimmune dialogue.
Funding GK is supported by the  Ligue contre le Cancer  (équipe labellisée);  Agence National de la Recherche (ANR) -Projets blancs ;  ANR  under the frame of E-Rare-2, the  ERA-Net for Research on Rare Diseases ;  AMMICa US23/ CNRS UMS3655 ;  Association pour la recherche sur le cancer (ARC) ;  Association "Ruban Rose" ;  Cancéropôle Ile-de-France ;  Chancelerie des universités de Paris  ( Legs Poix ),  Fondation pour la Recherche Médicale (FRM) ; a donation by Elior;  European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR) ;  Gustave Roussy Odyssea , the  European Union   Horizon 2020 Project Oncobiome ;  Fondation Carrefour ;  High-end Foreign Expert Program in China  [ GDW20171100085 ],  Institut National du Cancer (INCa) ;  Inserm (HTE) ;  Institut Universitaire de France ;  LeDucq Foundation ; the  LabEx Immuno-Oncology  ( ANR-18-IDEX-0001 ); the  RHU Torino Lumière ; the  Seerave Foundation ; the  SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE) ; and the  SIRIC Cancer Research and Personalized Medicine (CARPEM).