dataesr/scientific-paragraphs-categorization huggingface dataset:
Homozygous carriers of the Hutterite (DSC2 c. 1660C > T)  [19]  or Naxos (JUP c. 2040_2041delGT)  [20]  founder variants were excluded from Group 1 and were regarded as separate groups. We performed the analysis using Microsoft Excel 2007 (Microsoft, Redmond, WA, USA) and IBM SPSS Statistics 25 (IBM Analytics, Armonk, New York, USA). To compare the outcomes, defined as the age of the first occurrence of one of the events listed in the composite endpoint, in different groups, we created Kaplan-Meier graphs and performed log-rank pairwise comparisons to determine different eventfree survival distributions. Variables were included in a multivariable Cox regression model, and correction for proband status and sex was performed.
Systematic Literature and Database Search The systematic PubMed literature search yielded 1 346 publications; the search performed in the ARVD/C Genetic Variants Database yielded 65 articles, of which 61 overlapped with the PubMed literature search. From a total of 1 350 articles, we identified 67 studies (Supplementary Table  2 ) describing patients with more than one variant believed to be associated with ARVC, which we used to create our study database (Fig. 1A ).
ARVC Multiple Variants Database Retrieving cases from the selected 67 publications and adding additional cases after contacting the related research groups, including those from the Dutch ARVC registry, resulted in a database containing 500 patients of interest. After de-duplicating patients published in more than one publication, 331 different multiple ARVC variant carriers (135 women and 196 men) were included. Most patients (n = 134; 40. 5%) were carriers of two heterozygous variants in two different genes (digenic form), 29. 3% (n = 97) were carriers of a homozygous variant (including 33 homozygous for the Naxos variant and 12 for the Hutterite variant), 24. 8% (n = 82) were compound heterozygotes with two different variants in one gene, 4. 8% (n = 16) had a combination of digenic form and compound or homozygous form, while 0.
g. ExAc database of ~ 60,000 exomes vs. gnomAD database of ~ 140,000 exomes and genomes), (2) the use of improved computational tools, (3) newly available patient information either published or in databases (e. g. HMD), such as the identification of more independent probands with similar phenotypes, (4) the availability of (more) Fig. 2  Kaplan-Meier survival analysis. Group 1 (double P/LP variant carriers), Group 2 (one P/LP variant carrier), and Group 3 (no P/LP variant carrier). A All. B, C All, stratified for sex. D, E All, stratified for proband status co-segregation data (underscoring pathogenicity), or lack of co-segregation (disputing pathogenicity), or (5) novel functional data supporting pathogenicity. In a recent study, rare variants associated with arrhythmogenic cardiomyopathy were reclassified in 31% of cases after 5 years of follow-up since 1996  [21].
In our dataset of patients carrying multiple desmosomal variants, we used guidelines based on the current ACMG criteria to identify patients carrying two or more reclassified P/LP variants in the desmosomal genes. This refinement showed that genotype, i. e. carrying multiple desmosomal P/LP variants, has an additional effect on the outcome. The control groups consisted of a group of patients (Group 2) carrying one desmosomal P/LP variant combined with a VUS or B/LB and another group of patients (Group 3) with a combination of two variants classified as either VUS or B/LB. Of note, no difference in outcome was found between these two latter groups. This could be because both groups are still too heterogeneous, and the effect of these variants remains unknown, emphasizing the need for additional functional and co-segregational analyses  [14].
Limitations and strengths Our analyses are limited by the incompleteness of reported data in the original studies. In addition, not all relevant genes were tested in all studies included. Therefore, the possibility cannot be excluded that a small number of patients included in our study had additional P/LP variants in those unanalysed genes. This may have led to an overestimation of the severity of phenotypes in subjects with one or no P/LP variants. Furthermore, the patients included in this cohort are from several large studies and registries describing ARVC patients and their family members. Unfortunately, we lack individual data regarding definite ARVC diagnosis or which task force criteria are fulfilled. Especially for family members, it is possible that they did not meet the diagnostic criteria or were asymptomatic.
Ligand preparation, protein preparation and molecular docking From the chemical structure of compound 33 (an N-alkylated tranylcypromine derivative) and the cofactor FAD (Extended data, Figure  S7A  and Figure  S7B , respectively  38  ), the covalent adduct was generated using the builder tool in the software MOE (Molecular Operating Environment) 2015. 10  39. An open-access alternative that can perform an equivalent function is AutoDock  40. In brief, the chemical structure of FAD was firstly obtained from a selected crystal structure of HsLSD1 (PDB entry: 6NQU, 41 % sequence identity) and then its structure was simplified since only the flavin ring of the cofactor is involved in the mechanism of action of this class of LSD1 irreversible inhibitor. Thereafter, the desired ligand was obtained by forming a covalent adduct between the amino group of the cyclopropyl core of compound 33 and the flavin ring of the cofactor.
Here, only the tricyclic ring of FAD was kept whereas the 5´-adenosyldiphosphoribityl group at position 10 of the flavin ring (oriented towards the interior of the protein) was removed using the builder tool in MOE. The generated model was prepared with the Schrodinger Protein Preparation Wizard tool using the OPLS_2005 force field where hydrogens atoms were added, partial charges were assigned, and energy minimisation was performed. To facilitate docking, the flavin ring of FAD was selected as the centroid to computationally prepare a 12 Å docking grid. Docking simulations were performed using the Glide docking software and the in-built Extra Precision (XP) scoring function in order to estimate the target-compound binding affinity (as expressed as XP score). Selecting default parameters, only 10 output poses (conformations) for ligand conformer were generated in the final step.
625% DMSO) control wells. Schistosomula/compound co-cultures were then incubated at 37°C for 72 h in a humidified atmosphere containing 5% CO 2. At 72 h, tissue culture plates were imaged under the same conditions (37°C for 72 h in a humidified atmosphere containing 5% CO 2 ) using an ImageXpress Micro XL high content imager (Molecular Devices, UK) with subsequent images processed for phenotype and motility. Briefly, the motility was captured from five successive images taken at six second intervals, for the phenotype four adjacent images were taken and tiled together to maximise larval numbers for phenotype analysis. All images were taken by a high content imaging microscope (ImageXpress Micro XL) controlled with Meta Xpress software (Molecular Devices, UK)  46. The phenotype and motility scores were used to evaluate whether a compound displayed anti-schistosomula activity; here, -0.
Miracidia were scored as fully transformed if the transformation process was completed, the sporocyst surface was fully formed, no cilia plates remained attached and normal movement was detectable. A miracidium was scored as partially transformed if the parasite was no longer swimming, assumed a rounded morphology and ciliated plates remained attached to the parasite surface. Dead parasites were identified if they did not show any signs of movement, extensive degradation was present at the surface and no flame-cell activity was evident. All statistical analyses were performed using a two-way ANOVA followed by least significant difference post-hoc correction. All analysis were performed using GraphPad software, version 7 (RRID:SCR_ 002798).
75 zoom factor) using the Leica Application Suite X. For each Z-stack, a total of 60 sections were acquired selecting the 488 nm and 405 nm fluorescent channels for egg autofluorescence and DAPI (nuclei) stain, respectively. Quantification of overall volume (mapped by the green autofluorescence) and content of vitellocytes (DAPI) for individual eggs was performed using Imaris v8. 2 (Bitplane, RRID:SCR_007370). All statistical analyses were performed using a nonparametric Student's t-test (Mann-Whitney test). All analysis were performed using GraphPad software, version 7 (RRID:SCR_002798).
A Z-stack, containing 60 sections, was generated for each microscopic image for each adult schistosome examined (six male and six female worms for each treatment). For the quantitative analysis, the fluorescent intensity of the DAPI (staining non-proliferating nuclei) and EdU (staining all dividing cells) channels were used to calculate the total volume (µm 3 ) occupied by each fluorophore using the Surface tool in Imaris v8. 2 (Bitplane, RRID:SCR_007370). The percentage of EdU positive nuclei was calculated by dividing the volume of the EdU channel by the volume of the DAPI channel  15. All statistical analyses were performed using a nonparametric Student's t-test (Mann-Whitney test). All analysis were performed using GraphPad software, version 7 (RRID:SCR_002798).
By default, in ChIPSeeker, the transcription start sites (TSS) region is defined from -3kb to +3kb. To produce metagene profiles, only the 5073 plus strand genes were filtered from the gff file. Compute Matrix of the DeepTools package  73  was used with the 'scale-regions' option, defining the region Body Length (distance in bases to which all regions are going to be fit) as 2,000 and up-and downstream distance of 2,000. PlotProfile of the same package served to produce images of metagene profiles evoking the "standard error" option. Significant differential peaks with adjusted p-value ≤ 0. 05 were retained for the analysis. Integrative Genomics Viewer (IGV) was used for visualisation of MACS generated BedGraph files and BED files.
Data visualisation Heatmaps of enriched ATAC-Seq reads in significantly different peak regions were generated with Heatmapper. Three datasets were generated for each sex: (i) the raw number of reads aligned to each peak region that was also used as input to DESeq2, (ii) raw number divided by total number of peaks per sample and (iii) the normalised output of DESeq2. As expected, all files delivered roughly the same clustered heatmaps. Only differential peaks were shown here. Average linkage was used as the clustering method; Manhattan was used as distance Measurement Method; clustering was applied to rows and columns.
05% Tween 20 (TBST). Following that, the membranes were probed with 1:2000 dilution of anti-H3K4me2 (ab32356, Lot GR84714-4, Abcam, RRID:AB_ 732924) overnight (at 4°C) in 5% fat-free dry milk in TBST. The blot was washed, incubated overnight at 4°C with 1:500 dilution of the secondary antibody (goat anti-rabbit Horseradish Peroxidase coupled antibody -Pierce #31460, Lot HB987318, RRID:AB_228341) in 5% fat-free dry milk in TBST. The blot was then developed by incubating with an enhanced chemiluminescence (ECL) substrate (Pierce) followed by CCD camera image acquisition. Acquisition time was adjusted to have maximum exposure without saturation. The detected bands were analysed with ChemiDoc software v4. 0. 1 with high sensitivity settings. For sample normalisation, the membranes were stripped by incubation at 50°C for 1 h in 62 mM TRIS-HCl pH 6.
Except for one sample (DMSO F2, highlighted by*), control (DMSO) treated, and compound 33 treated female samples were clearly clustered, suggesting the high quality of the sequencing data across a library of 24 samples (each sample was derived from an individual worm). Similar conclusions were drawn from the male dataset (Extended data, Figure S5C  38  ). Of these statistically enriched ATAC-Seq signals, 87% (732/844) and 76% (1,597/2,107) of the differentially identified loci were found in female and male gene bodies, respectively (Extended data, Table  S4E  66 ). Those lists of genes were further segregated depending on whether the ATAC-Seq signals were differentially associated with compound 33 (negative value of log 2 FC -fold change) or control treated samples (positive value of log 2 FC) (Extended data, Table  S5A  and Table S6A  66  , female and male respectively), keeping in consideration that unique genes may be associated with multiple ATAC-seq peaks (up to four and 15 different peaks for the female and male datasets, Extended data, Table  S5B  and Table S6B  66  , female and male respectively).
mansoni worms by Wendt et al. 100 (Figure  10 ). For both sexes, we performed a hypergeometric distribution analysis on the two datasets (ATAC-seq vs scRNA-Seq) to calculate the probability that the ATAC-Seq signal is over-represented in genes differentially expressed within distinct cell clusters. In females, ATAC-Seq loci affected by compound 33 treatment were over-represented (PMF > 0. 1, outlined in bold boxes) in genes differentially expressed/enriched in the esophageal glands, the germinal stem cells (within the ovary), the hes2+ stem cells (a neoblast progenitor population), the S1 stem cells (within the vitellaria) and the late female germinal stem cells within the ovary (Figure  10A ). The genes smp_312640 (expression enriched in the late female germ cell cluster) and smp_200410 (expression enriched in both GSC clusters) represent two examples where compound 33 statistically affects ATAC-Seq signals found in the intragenic region (3´-UTR and intron, respectively as shown in Extended data, Figure S6  38  ).
To explore this, homology modelling and compound docking were performed (Figure  11 ). As previously published  19  , the homology model of the parasite enzyme was generated using the elucidated HsLSD1 structure (PDB entry: 2V1D, Figure  11A )  105. The predicted 3D model of SmLSD1 shows the main features of this protein, particularly the catalytic domain (Amino Oxidase-Like domain -AOL domain shown in green) containing the histone substrate (in brown), cofactor binding pocket and the Tower domain (in blue) with its antiparallel coiled-coil conformation 106. In order to predict the binding mode of compound 33 (Extended data, Figure  S7A  38 ) to SmLSD1, the N5 adduct of this compound with the flavin ring of the FAD (Extended data, Figure  S7B  38 ) cofactor was prepared (Extended data, Figure S7C  38  ) and used as a ligand for molecular docking to the SmLSD1 homology model.
• Table  S4A. xlsx -List of the 71,859 ATAC-Seq peaks found in the female dataset • Table  S4B. xlsx -List of corresponding 844 genomic loci associated to statistically significant ATAC-seq differences (adjusted p-value ≤0. 05) following compound 33 treatment (female dataset). • Table  S4C. xlsx -List of the 84,997 ATAC-Seq peaks found in male dataset. • Table  S4D. xlsx -List of corresponding 2,107 genomic loci associated to statistically significant ATAC-seq differences (adjusted p-value ≤0. 05) following compound 33 treatment (male dataset). • Table  S4E. xlsx -List of female and male genes associated to statistically significant ATAC-seq differences between compound 33 and mock treatments. • Table  S5A. xlsx -List of the 844 genomic loci associated to statistically significant ATAC-seq differences (female subset).
Acknowledgments KFH, GP and AB thank the  Welsh Government, Life Sciences Research Network Wales  scheme and the  Wellcome Trust  ( 107475/Z/15/Z ) for financially supporting this project. JHK and PAC thank the  NIH  ( GM62437 ). DL and CG acknowledge the support provided by the framework of the " Laboratoires d'Excellences (LABEX) "  TULIP  ( ANR-10-LABX-41 ). With the support of  LabEx CeMEB , an  ANR « Investissements d'avenir » program  ( ANR-10-LABX-04-01 ) and its  Plateforme Epigénomique Environnementale. Eve Toulza and the  Bio-Environment  platform team performed the Illumina sequencing whose cost was covered by the  Joy Welch Research Fund : Post-doctoral Grants  2021/22- Funding Call. We thank past and current members of the  Hoffmann group  and  Miss Julie Hirst  for contributions to S.
Cells Huh7-Lunet cells and Huh7-Lunet T7 cells have been described before  33  , as well as the Con1 subgenomic replicon clone 9-13  34  (gt1b, GenBank accession number AJ238799) and LucubineoJFH1 35 (gt2a, GenBank accession number AB047639), along with the HAV replicon cell lines 36. Huh 7. 5 cells were a generous gift from Charles Rice. Huh 7. 5 TLR3, RIG-I and MDA5 were generated in a previous study  14. The HepaRG LGP2 KO cell line cell line was preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. described recently  37. HepG2 were kindly provided by H. P. Dienes. RIG-I KO and MDA5 KO cells were generated by CRISPR/Cas9 in this study. All cell lines used in this study were validated and free of mycoplasma. PHH were isolated from liver resections of patients undergoing partial hepatectomy as described previously  14.
Viruses For HCV infection of Huh7. 5 cells, strain Jc-1 was used. For infection of uPA-SCID mice with humanized liver HCV WT isolates from sera of an infected patient (gt1b, strain GLT1 38 ) or of strain mH77c (gt1a 39 ) was used. For HAV, genotype IA WT strains were isolated from patient stool samples. Huh7. 5, HepG2 and HepaRG cells were infected with Hepatitis A virus strain HM175/18f, genotype IA. For HAV infection of humanized mice, virus of GLT1 serum was obtained from a male patient under immunosuppression with tacrolimus, mycophenolic acid and methylprednisolone because of status post re-liver-transplantation. The local ethics committee approved data collection and analysis (ethics vote: S-677/2020, Heidelberg University, ethics committee of the medical faculty). HAV WT was obtained from stool samples of two anonymous donors, through allowance of Apulia Region, Italy (DGR n.
ACKNOWLEDGMENTS The authors thank  Rahel Klein ,  Ulrike Herian  and  Lieven Verhoye  for excellent technical assistance. We are grateful to  Vibor Laketa  and the  Infectious Diseases Imaging Platform (IDIP ) for microscopy support. We thank  Yuri Kusov  for the HAV subgenomic replicon,  Stanley Lemon  for a plasmid encoding HAV full-length genome and  Verena Gauss-Müller  for the HAV 3C antibody. Huh7. 5 cells and the HCV NS5A antibody "9E10" were generous gifts of  Charles M. Rice. We thank  Takaji Wakita  for the JFH-1 isolate. In addition, we thank  Zhenfeng Zhang ,  Ann-Kathrin Mehnert ,  Philipp Klein ,  Christopher Neufeldt  and  Mirko Cortese  for helpful discussions.
Methodology of Research Work In the context of the energy transition, it was observed through an initial literature review that the term is principally entrenched in French literature. Consequently, this warrants the introduction of low-tech in English literature. Therefore, this research work aims at using low-tech as an assessment framework for in-practice energy flexibility solutions. To carry out the evaluation, it was necessary to categorize energy flexibilities into three main types: supply-side energy flexibilities, demand-side energy flexibilities, and energy storage systems. Despite some degree of overlap between these three categories, there is enough distinction between them to present energy flexibility solutions in this manner. Thus, Google Scholar and Web of Science were used as resource databases to search for existing energy flexibility solutions that fell within the three categories.
Funding: This work was partially supported by the  ANR  project  ANR-15-IDEX-02 , the eco-SESA program (https://ecosesa. univ-grenoble-alpes. fr/, accessed on 3 April 2023), the  Observatory of Transition  for Energy (https://ote. univ-grenoble-alpes. fr/, accessed on 3 April 2023), and a grant from the  French government  under the  PIA, IRT Nanoelec , bearing the reference  ANR-10-AIRT-05.
Methods In this systematic analysis for the Global Burden of Disease Study, osteoarthritis prevalence in 204 countries and territories from 1990 to 2020 was estimated using data from population-based surveys from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, 42 countries for hand osteoarthritis, and US insurance claims for all of the osteoarthritis sites, including the other types of osteoarthritis category. The reference case definition was symptomatic, radiographically confirmed osteoarthritis. Studies using alternative definitions from the reference case definition (for example self-reported osteoarthritis) were adjusted to reference using regression models. Osteoarthritis severity distribution was obtained from a pooled meta-analysis of sources using the Western Ontario and McMaster Universities Arthritis Index.
Research in context Evidence before this study The Global Burden of Disease (GBD) study is the only source of global, regional, and country estimates of osteoarthritis burden over time. We have previously reported on osteoarthritis of the hip and of the knee, but here we also report on osteoarthritis of the hand and of other sites for the first time. Input data for GBD osteoarthritis models were identified through a systematic review and use of US insurance-claims data. We did a systematic review of population-based epidemiological studies of osteoarthritis reporting on osteoarthritis prevalence published between 1980 and the end of 2019 in PubMed using the search terms (("osteoarthritis" AND ("epidemiology" OR "prevalence")) AND "humans") AND ("population" OR "population groups" OR ("population" AND "groups")).
These data provide strong support to address high BMI as a modifiable risk factor to reduce osteoarthritis burden. Health system planning would be further aided by quantifying additional osteoarthritis risk factors, such as injury and occupational hazards. The presented evidence should contribute to developing global health initiatives for osteoarthritis during the 2021-30 decade of healthy ageing. definitions, data collection, and disease modelling methods. Studies done between 1980 and 2019 from all available global locations were identified using PubMed (appendix pp 3-4). These data were used to produce prevalence estimates for each osteoarthritis site between the years 1990 and 2020, across the age range (>30 years), for male and female sexes, and for all GBD locations (appendix pp 1-2 presents a description of GBD superregions, regions, and country groupings).
Case definitions The GBD reference case definition for both hip and knee osteoarthritis is symptomatic osteoarthritis radiographically confirmed as Kellgren-Lawrence grade 2-4 (definitive osteoarthritis). [24] [25] [26]  Kellgren-Lawrence grade 2 indicates the presence of one defined osteophyte in the joint, grade 3 indicates the presence of several osteophytes and joint-space narrowing, and grade 4 indicates the same criteria as grade 3 in addition to bone deformity. Symptomatic osteoarthritis requires reported pain for at least 1 month out of the past 12 months. The main sources of input data for the hip and knee osteoarthritis models were cross-sectional, populationbased survey data from locations worldwide and statelevel US insurance claims data captured by International Classification of Diseases (ICD)-9 four-digit or five-digit codes starting with 715 specific to knee or hip, and ICD-10 codes M16 and M17.