dataesr/scientific-paragraphs-categorization huggingface dataset:
Funding H. Chebaicheb 's PhD grant is supported by the LCSQA funded by the  French Ministry of Environment. IMT Nord Europe  acknowledges financial support from the  Labex CaPPA project , which is funded by the  French National Research Agency (ANR)  through the  PIA (Programme d'Investissement d'Avenir)  under contract  ANR-11-LABX-0005-01 , and the CLIMIBIO and ECRIN projects, both financed by the  Regional Council "Hauts-de-France " and the  European Regional Development Fund (ERDF). IMT Nord Europe  and INERIS participated in the  COST COLOSSAL Action   CA16109. The ATOLL site is one of the  French ACTRIS National Facilities  and contributes to the  CARA program  of the LCSQA funded by the  French Ministry of Environment.
Included Population-Based Studies Eleven population-based cohort studies participating in the E3 Consortium were included in the present study. 13 All studies contributed data to the glaucoma analyses, and 10 studies were included in the IOP analyses. The E3 Consortium is a collaboration of European population-based and cohort studies that aims to increase understanding of eye disease and vision loss. 13 Participants were recruited between 1991 and 2017 from the following countries: France, Germany, Greece, the Netherlands, Norway, Portugal, Russia, and the United Kingdom. All studies adhered to the tenets of the Declaration of Helsinki and had local ethical committee approval. All participants gave written informed consent before examination.
We considered only IOP measurements obtained at the same time as systemic medication use ascertainment, assuming that any IOPaltering effects may be apparent only while the drug is being used. We considered each participant's IOP as the arithmetic mean IOP of both eyes; if IOP was available for only 1 eye, we considered that value as the participant's IOP. Seven studies collected medication data based on medical prescriptions and medication containers; 4 studies used self-reported (questionnaire) data. Systolic blood pressure (SBP) measurements were performed at the research centers and collected in all studies. SBP measurements were not adjusted for antihypertensive treatment. Total cholesterol was measured in blood samples collected at the research center and was available for 8 of 11 studies.
Diabetes mellitus diagnosis ascertainment method was variable across studies, and, in most cases, multiple criteria were used: selfreported DM diagnosis, physician-confirmed DM diagnosis, use of antidiabetic medications, and fasting and nonfasting glucose of more than a certain cutoff or hemoglobin A1c level of more than certain cutoff. Ethnicity was determined in 8 of 11 studies. Descriptive data for the contributing studies can be viewed in Table  1. Detailed study methods and protocols are available in the Supplemental Methods (available at www. aaojournal. org).
g. , glibenclamide and chlorpropamide). The Ural Eye and Medical Study did not have medication data available specified per ATC code but did have data on diuretics, systemic b-blockers, CCBs, and reninangiotensin system (RAS) inhibitors; therefore, we included this study only in those broader analyses. For antihypertensive medications, we additionally determined the use of monotherapy (i. e. , use of only 1 antihypertensive medication class).
Subsequently, we conducted random-effects meta-analyses, given the heterogeneity of study participants and study designs. For analyses of glaucoma status, we repeated metaanalyses after exclusion of studies with nonobjective glaucoma ascertainment (i. e. , self-reported data only). Moreover, we performed sensitivity analyses, including only patients with glaucoma whose disease was defined as open-angle glaucoma (primary or secondary was not defined). For IOP as an outcome, these sensitivity analyses were not performed because we aimed to include the full range of IOPs from the complete population (regardless of glaucoma status). Statistical analyses were performed using SPSS software version 25. 0 (SPSS, Inc. ) and RStudio version 4. 0. 0 (R Foundation for Statistical Computing) with the add-on package meta.
Insulin and sulfonylureas have been associated with higher mean IOP. 11 We were limited by sample size in the analyses for the antidiabetic medications because the prevalence of glaucoma in a population-based study often is only 1% to 8% and the prevalence of DM in such populations is only 3% to 18%. This makes the number of participants with glaucoma and DM even lower, leaving the sample of participants with DM and glaucoma who are treated with, for example, metformin very limited. Moreover, because most of the data in our study was collected > 10 years ago, we were able to examine only frequently used antidiabetic medications at the time (i. e. , insulin, biguanides, and sulfonylureas) and not some of the newer classes of antidiabetic medications (e. g. , sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists).
In the primary meta-analyses, we included both objectively and nonobjectively ascertained patients with glaucoma. For the nonobjectively ascertained patients with glaucoma, it was not determined which glaucoma subtype was present. Therefore, we performed sensitivity analyses excluding nonobjectively ascertained patients with glaucoma; this decreased the sample size and thus limited the statistical power. Also, not all objectively ascertained patients with glaucoma underwent gonioscopy (Table  1 ). This made it less feasible to discriminate robustly between open-angle or angle-closure disease. It is possible that adding other subtypes of glaucoma may have added noise to our data and may have affected the observed associations. We tried to mitigate this by performing sensitivity analyses including only patients with open-angle glaucoma (Table  S7 ).
Acknowledgments The authors thank all the participants who have been part of the project and the many members of the study teams who have enabled this research;  Dr Ronny Baber  (Head of the  LIFE-Biobank  and  LIFE Preanalytical Laboratory at University Hospital Leipzig, Leipzig, Germany ) and  Dr Anja Willenberg  ( Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Leipzig, Germany ) for access to  LIFE-Adult Study laboratory data ; and  Yvonne Dietz  (LIFE) and  Melanie Eberl  ( LIFE ) for data management.
Study oversight and participants We conducted a retrospective study in eight general hospitals and 27 university hospitals in France. This study was approved by the Institutional Review Board of Rouen University Hospital (N°E2021-34). Inclusion criteria were as follows: (i) patients with a diagnosis of PG occurring during pregnancy, based on suggestive clinical features (blisters and/or urticarial skin lesions), (ii) direct immunofluorescence showing IgG and/or C3 deposit along the dermal-epidermal junction, (iii) detection of anti-BP180 IgG antibodies by ELISA (commercial kit Euro-immun threshold min 20 IU/ml-max 200 IU/ml) performed at the time of PG diagnosis and (iv) patients' clinical characteristics and evolutive data available from the beginning to the end of the pregnancy. Patients whose PG started after delivery were excluded.
Study assessments and outcomes Patients with PG followed between 1 January 2009 and 31 December 2019 in the participating centres were identified using the computerized database of the immunology laboratory of the French reference centre for autoimmune bullous skin diseases in Rouen. The available serum samples with a BP180 ELISA value equal to or higher than 200 IU, which corresponds to the highest quantitative value measurable by the commercial kit used, were secondarily diluted in accordance with the recommendations of the reagent manufacturer, in order to determine the precise anti-BP180 antibody titters. Patients' clinical characteristics at diagnosis and their clinical course were retrospectively retrieved from dermatology and obstetrical medical records. Pregnancy outcomes reported to be associated with PG in the literature were recorded, that is prematurity (birth before 37 weeks of pregnancy), intrauterine growth restriction (IUGR, i.
5 to assess the overall diagnostic value. The threshold that produced the highest sum of sensitivity and specificity (i. e. highest Youden's index) was considered the most discriminating. Internal cross-validation of optimal threshold selection based on bootstrap resampling was performed using 2000 bootstrap replicates. All statistical analyses were performed using SAS version 9. 4 software (SAS Institute) and R software (R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www. R-project. org/). For all analyses, a p-value less than 0. 05 was considered statistically significant.
Baseline characteristics and clinical course of patients Among the 115 patients with PG identified from the database, five patients had a PG which started after delivery, one patient had a voluntary termination of pregnancy, and the outcome of pregnancy could not be recorded in 14 patients. Finally, 95 women with PG of which 19 were primiparous were included and analysed. Their mean age was 32. 9 ± 6. 0 years, which was slightly older than the 30. 3 years mean age of pregnant women in France. Main clinical data are summarized in Table  1. Median anti-BP180 antibody ELISA value at the time of diagnosis was 144 IU (IQR 96-186; 95% CI: 122-166). Patients with blisters had higher anti-BP180 ELISA values than those without blisters (median 159 IU; IQR 112-192; 95% CI 129-180 vs. 104 IU; IQR 84-144; 95% CI: 83-144; p = 0.
In their series, the presence of blisters was associated with a decreased gestational age at delivery and prematurity but they did not evidence any relationship with other APO, including small for gestational age at birth. 4  Unfortunately, anti-BP180 antibody ELISA values were not recorded in their study. [9] [10]  We observed that anti-BP180 antibody ELISA values higher than 150 IU were only associated with the occurrence of IUGR, while we did not evidence any relationship between these anti-BP180 ELISA values and other types of APO such as prematurity or small for gestational age at birth. Not applicable (without delivery) -Unknown 0-0 a Missing data for five patients who had delivery of an alive baby without information for IUGR, SGA, preterm labour or prematurity. We estimated that a threshold of 150 IU of anti-BP180 ELISA value provided a 30% positive and 91% negative predictive value with an adjusted OR = 5.
Comparative Modeling of YF MTase 2017 We modeled the NS5 MTase domain of the prototype YFV isolated in 2017 (GenBank: KY885000) and the variant carrying the three amino acid changes (R 101 K, V 138 I, and G 173 S) using Modeller software version 10. 1. The search for a suitable template was performed on the Swiss-model server  [39]. The PDB structure from the vaccine YFV complexed with S-adenosyl-L-homocysteine (SAH; 3EVB)  [22]  was employed as a template, sharing 94. 32% identity with the YFV 2017 sequence. The template and target sequences were aligned using the "align2d" function of Modeller  [40]. A total of 100 models were obtained for each MTase variant using the "automodel" routine of the Modeller. Each model was optimized using the variable target function method (VTFM) for 300 iterations and molecular dynamics (MD) in slow mode.
Synthesis of YFV cDNA Infectious Clone The methodology employed in this study was based on the strategy developed for the infectious clone Zika virus Rio-U1  [43]. The cDNA genome was derived from the YFV isolate ES-504 (GenBank: KY885000). This YFV was isolated from a non-human primate belonging to the Alouatta guariba clamitans species in the state of Espírito Santo, Southeastern Brazil, in February 2017. The cDNA was previously obtained by RT-PCR and sequenced  [2, 6]. We amplified the ES-504 cDNA to obtain four fragments covering the entire genome and presenting overlapping regions (Figure  2A ). The employed primer sets are listed in Supplementary Table  S1. The amplification primers of fragments 2, 3, and 4 were used to insert silent mutations to create restriction sites Mlu I, Kpn I, and Spe I, allowing directional cloning in plasmid vectors.
Plaque Phenotype Assays The plaque phenotype assay was conducted as described elsewhere  [45]. In summary, Vero cells seeded at 40,000 cells/cm 2 were infected with 10 PFU, 20 PFU, and 40 PFU of each virus. After infection, cells were overlaid with 0. 5% agarose prepared in Earle's 199 medium (Gibco, Waltham, MA, USA) supplemented with 5% fetal bovine serum (FBS; Cutilab, Campinas, SP, Brazil), 0. 25% sodium bicarbonate (Sigma-Aldrich, Saint Louis, MO, USA), and 40 mg/mL gentamicin (Gibco, Waltham, MA, USA) and further incubated at 37 • C and 5% CO 2 for 7 days. The cells were fixed in 10. 0% formaldehyde and stained with 0. 4% violet crystal. Images of the plates were analyzed using ImageJ software version 1. 51 to measure plaque areas. The results were plotted and statistically analyzed using GraphPad Prism software 8.
02 in a final volume of 0. 5 mL. The cell medium was discarded, and the inocula were adsorbed in the cell monolayer for 1 h. After that, the viral suspension was discarded, the appropriate cell medium was added to the monolayer, and the cells were incubated for 5 days. An aliquot of cell supernatant was collected every 24 h and titrated by plaque assay  [45]. The viral titers were transformed in log 10 and plotted in a dispersion graph for analysis. The statistical analyses were conducted in GraphPad Prism 8 software.
Euthanasia was performed with intraperitoneal administration of three times the previous dose of the Ketamine/Xylazine cocktail, followed by cervical dislocation. This experimentation was reproduced in quadruplicate, totalizing 16 animals infected with each viral sample. Average survival time (AST), percentage of mortality, clinical scores, and body weight loss were calculated and analyzed in GraphPad Prism 8 software. Statistical analysis of Kaplan-Meier survival curves was performed by log-rank test (Mantel-Cox).
Expression and Purification of YFV NS5 MTase Domain For the expression and functional studies, the sequence corresponding to the methyltransferase domain of YFV NS5 (aa 1-270) was amplified using specific primers with Phusion DNA Polymerase and reagents (Thermo Fisher Scientific). The amplicon was obtained from ES-504 isolate (GenBank: KY885000) and then cloned into a pETM-11/LIC plasmid vector with an N-terminal His6 tag. The vector plasmid was modified with the deletion of the connector sequence and the TEV cleavage site between the His6 tag and the MTase domain by PCR with Phusion DNA Polymerase. The variant carrying the reverted amino acids of the molecular signature (R101K, I138V e S173G) was obtained through site-directed mutagenesis using QuikChange II XL Site-Directed Mutagenesis Kit (Agilent).
Before a final drying step, the unincorporated [3H]SAM was washed from the DEAE filters with 10 mM ammonium formate (pH 8. 0), with H 2 O, and with absolute ethanol. At last, the filters were placed into plastic bags with BetaplateScint (Wallac) scintillation fluid and sealed. The transferred [3H]methyl groups onto RNA substrates were quantified in counts per minute using a Wallac 1450 MicroBetaTriLux liquid scintillation counter. The IC 50 values of SAH, sinefungin and cap analogs were determined with GraphPad Prism software 8 using the log (inhibitor) versus response variable slope equation.
Structural Analysis of the Molecular Signature in the NS5 MTase Domain A previous study on the circulating YFV 2016-2019 first explored the molecular signature in computational tridimensional structure analyses of NS3 and NS5 viral proteins  [6]. Here, we reproduced the comparative modeling methodology, focusing exclusively on the MTase domain, to review the structural localization and potential influence of the three residues characteristic of YFV 2016-2019, which caused the outbreak in Southeastern Brazil. Thus, we modeled the MTase domain of YFV 2016-2017 NS5 protein by homology, using the crystallographic structure of YFV 17D MTase (PDB: 3EVB), sharing 94. 32% of identity and 100% coverage, as a template. The YFV 2016-2019 molecular signature in the MTase consists of residues R, I, and S in positions 101, 138, and 173, respectively.
These residues are adjacent with distances between Cα from 101 to 138 and 138 to 173 of about 10Å. These amino acids are not directly involved in binding or catalytic interactions; however, they are closer to the methyl donor (SAM) binding site (Figure  1 ). We also utilized the PyMOL software to change the three amino acid alterations, reverting these residues to the corresponding previously circulating YFV 2000-2010, here named as MTase 2010. The substitutions were Arg (R) to Lys (K) in position 101, Ile (I) to Val (V) in position 138, and Ser (S) to Gly (G) in position 173. All three-residue changes are conservative and have little impact on the 3D structure. Notably, residues with longer lateral side chains substituted the residues of MTase 2010. For instance, the R residue in 101 (MTase 2017) has an additional amino group in the side chain than the K residue (MTase 2010).
Acknowledgments: We are thankful to  Ieda Pereira Ribeiro ,  Déberli Ruiz Fernandes ,  Lidiane de Souza Menezes Raphael ,  Marta Pereira Santos  and  Alexandre Araújo Cunha dos Santos  for the technical support in the completion of this work. We are also grateful to the  Plataforma Genomica-Sequenciamento de DNA-RPT01A-Rede de Plataformas Tecnológicas FIOCRUZ  for the services.
Induction of muscle contraction and contractile force measurement Muscle contractions were induced by electrostimulation using two transcutaneous surface electrodes connected to a constant-current stimulator (DS7A, Digitimer, Herthfordshire, United Kingdom). One electrode was placed at the heel level and the other one was located just above the knee joint. Electrical signal coming out from the force transducer of the ergometer was amplified (Two operational amplifiers: AD620 and OP497, Analog Devices, Norwood, MA, USA, with a total dB gain: 70dB @ 0-5 kHz bandwidth), continuously monitored and recorded on a personal computer using a Powerlab 16/36 data acquisition system (AD Instruments, Sydney, Australia) and a dedicated software (LabChart 8, AD Instruments, Sydney, Australia). The digital signal was converted to force (mN) according to a linear calibration curve.
Moderate-intensity exercise protocol Function and bioenergetics of the posterior hindlimb muscles were evaluated throughout a 6-min moderate-intensity exercise consisting of maximal isometric contractions repeated at a frequency of 1 Hz, induced with square wave pulses (0. 5-ms duration). Individual maximal stimulation intensity was determined by a progressive increase of the stimulus intensity until there was no further force increase. Force parameters were acquired with LabChart software (AD Instruments, Oxford, UK). Peak force (Pf, mN) was quantified. Total force production (TFP) was computed as the sum of each twitch. Specific parameters (sPf, sTFP) were normalized to posterior hindlimb muscles volume (cm 3 ) computed from anatomic hindlimb MR images. Force increase (%) was defined as the ratio between the maximal and initial force values.
Multimodal MR data acquisition Ten consecutive non-contiguous axial slices (1-mm thickness, spaced 0. 25 mm) covering the region from the knee to the ankle were selected across the lower hindlimb. RARE images (Rare factor = 8, effective echo time = 35. 29 ms, actual echo time = 11. 76 ms, repetition time = 5000 ms, one accumulation, 20 x 20 mm field of view, 256 x 192 matrix size, acquisition time = 3 min 14 s) were recorded at rest in order to assess muscle volume. Posterior hindlimb muscles region was manually delineated on each of the 6 largest slices. Then, muscle volume of each slice was extracted using the FSLeyes software  (33). Total muscle volume (cm 3 ) was calculated using the truncated cone volume formula considering slice and gap volumes. Multiecho T2-weighted images (16 echo times equally spaced from 7.
28 ms to 116. 59 ms, 2000-ms repetition time, one accumulation, 20 x 30 mm field of view, 256 x 256 matrix size, total acquisition time = 8. 32 min, slice thickness = 1 mm, slice gap = 1 mm) were recorded at rest. T2-weighted images were processed to generate T2-maps on a pixel by pixel basis by fitting the corresponding data with a single exponential function. Mean T2 values of hindlimb muscles were measured on T2 maps and averaged on the 2 largest consecutive slices from the outlined regions of interest. The corresponding values were quantified for total gastrocnemius (GA) muscle and its right, central and left parts. Measurements were also performed for the tibialis anterior (TA). The averaged T2 of water protons illustrates the molecular environment together with the water mobility. 31 P-MR spectra (8 kHz sweep width; 2048 data points) from the posterior hindlimb muscles were continuously acquired before (rest period; 4.
MR Spectroscopy data processing MRS data were processed using custom-written routines in Python  (34)  integrating the AMARES Fortran code  (35)  from jMRUI (http://www. jmrui. eu/). Relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP were obtained from 31 P-MR spectra using the AMARES-MRUI-based time domain fitting routine including appropriate prior knowledge for the ATP multiplets  (34). Absolute amounts of phosphorylated compounds were expressed taking into account a 5-mM β-ATP basal concentration  (36). The PCr relative concentration was expressed relative to the PCr content at rest which was set at 100%. Intracellular pH was calculated from the chemical shift of the Pi signal relative to PCr according to the formula (37): pHi = 6. 75+log[(3. 27-δPi)/(δPi-5.
Data treatment. We constructed two data sets that were used for further analyses. First, we identified the number of expressed gene isoforms in the Atacama plant species transcriptome data set. To get these numbers, we counted the total number of genes per reaction for each annotated reaction. This analysis provided a first matrix which served as the basis for the reaction enrichment analysis (Fig. 1 , Tab. S1). Second, we identified highly expressed genes in Atacama species. To do this, we took the top 10% expressed genes from each of the 32 Atacama plant species transcriptome, as well as the top expressed genes from the 17 related Sister species for which raw sequencing data were available  (Eshel et al. , 2021). Top expressed genes that were not associated with any reaction were removed.
1, Tab. S2). Reaction enrichment analysis. Reaction enrichment analysis was performed using the two data matrices produced in the previous section: the number of expressed gene isoforms or qualitative expression levels for genes that were annotated to enzymatic reactions. First, exclusive reactions from Atacama or Sister species were extracted (Tab. S3). Second, common reactions (detected in at least one species in each set) were identified. We compared the number of expressed gene isoforms annotated to a reaction in any given Atacama species to the corresponding number of expressed gene isoforms annotated to the same reaction in the Sister species. We did this comparison using the entire data set or partitioned by vegetation belt (i. e. Prepuna, Puna, Steppe). Reactions were considered more diverse (i.