dataesr/scientific-paragraphs-categorization huggingface dataset:
We performed the PCA to observe the grouping according to host strain using picard  70. For nuclear mapping, the reads were mapped against the reference genome using bowtie2  68  with the -very-sensitive-local preset option. Potential optical or PCR duplicates were removed using Picard tools  70. Variant identification. Variant calling was performed using the GATK-4. 0. 11. 0 package  28. First, we performed haplotype calling, and the resulting gvcf files were merged into a single gvcf file using the same GATK package. Variants were then called, and only SNPs were extracted among all variants. The number of identified SNPs was 66,529,611. The SNPs were filtered out if their QualByDepth score was less than 2, if FisherStrand score was higher than 60, RMSMappingQuality was less than 40, MappingQualityRankSumTest score was less than -12.
A 75 μL solution of insecticide or control sample was overlaid on the top of the diet in each well and left to air dry before adding a single neonate in each well. Control treatments included distilled water and resulted in <5% mortality in all bioassay replicates. After treated diet air-drying, one neonate was transferred to each well, and sealed trays were maintained in incubators at 27 °C with a 16:8 (light:dark) photoperiod and 60-80% relative humidity. Bioassays were replicated four (deltamethrin) or two (deltamethrin + PBO) times, with each toxin concentration tested with 16 insects per bioassay replicate. Mortality was scored after 7 days and used for probit analysis in the POLO-PLUS software package  76  to estimate concentrations killing 50% of the individuals (LC 50 ) and corresponding 95% confidence intervals.
Acknowledgements This work was supported by a grant from the  department of Santé des Plantes et Environnement at Institut  national de la recherche agronomique (adaptivesv). Partial support for this project was also provided by  Agriculture and Food Research Initiative Foundational Program  competitive grant No. 2018-67013-27820  from the  USDA National Institute of Food and Agriculture. We also acknowledge  Yutao Xiao  ( CAAS ) for discussions on this paper and  Claire Lemaitre  ( INRIA ) for CNV identification.
Data availability The reference genome assembly generated in this study is available at NCBI (JACWZW000000000), together with raw PacBio reads and Hi-C data (PRJNA662887). The reference genome assembly is also available at BIPAA (www. bipaa. genouest. org/sp/ spodoptera_frugiperda). The resequencing data in this study are available at NCBI SRA (PRJNA494340, PRJNA577869). The vcf files generated in this study are available at Zenodo  77. Raw data used to generate figures are available as source data files within the Supplementary Materials, together with R scripts used to generate corresponding figures. Raw data used to generate Supplementary figures are also available as a source data file within the Supplementary Materials.
Serum Biomarkers At baseline and at each follow-up visit, a biochemical dataset including liver and renal function tests, virological values, and biochemical parameters for calculating FibroTest (FT), Fibrosis 4 (FIB-4), and aspartate-aminotransferase-to-platelet ratio index (APRI) was assessed. Beyond that, fasting samples were prospectively collected for measurements of lipids (serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides) and diabetic values (HbA1c, serum fasting glucose (FG), and serum insulin). Subjects with HOMA-IR levels >3 were defined as IR, as previously described  [23]. HOMA-IR was calculated according to the homeostatic assessment model: fasting glucose (mmol/L) × fasting glucose (mmol/L)/22. 5. FibroTest is a patented fibrosis marker which was developed by BioPredictive (Paris, France).
Statistical Analysis Data were expressed as mean ± standard deviation, if normally distributed, and as median and interquartile-range (IQR), if not normally distributed. Associations between categorial variables were tested by Spearman's correlation coefficients and their associated probability. Comparisons between groups were assessed by using the Mann-Whitney U-test. Friedman's test was carried out to detect longitudinal differences of metabolic parameters and noninvasive fibrosis assessments during 24 weeks of follow-up. A p value of less than 0. 05 was judged to be statistically significant. All analyzes were performed by using IBM SPSS 26. 0 statistical software package (SPSS/IBM, Munich, Germany).
The spectral data were acquired on an Autoflex Speed MALDI-TOF/TOF mass spectrometer equipped with a Smartbeam laser, using FlexControl 3. 4 and FlexImaging 3. 0 software packages (Bruker Daltonics). Ions were detected in positive linear mode over a mass range of m/z 2,000-20,000 with a sampling rate of 0. 63 GS/s. The lateral spatial resolution was set to 75 μm, and a total of 500 laser shots were accumulated per pixel at constant laser power, using random movement within each pixel. The deflection was set at an m/z of 1,500 and laser focus at medium. Analyses were performed using a detector gain of 2. 69 V, ion source voltage 1 at 19. 5 kV, ion source voltage 2 at 18. 15 kV, and lens voltage at 7 kV. Spectral data were loaded into SCiLS Lab 2016 software (http://scils. de/; Bremen, Germany).
The matrix used was α-cyano-4-hydroxycinnamic acid matrix at 7 mg/mL in water/acetonitrile 50:50 (v/v) with 0. 2% trifluoroacetic acid. The mass spectrometer used to acquire the protein fingerprinting was an Autoflex Speed MALDI-TOF/TOF with a Smartbeam laser, using FlexControl (version 3. 4) software (Bruker Daltonics GmbH, Bremen, Germany). A total of 4,000 spectra were accumulated randomly per sample. The laser power was constant for all the samples, and the laser focus was set at medium. Ion detection was done in linear mode at a mass range of m/z 1,000-10,000, with a sampling rate of 0. 31 GS/s. Acquisition deflection was set at m/z 1,000. The detector gain was set at 2,500 V, the ion source voltage 1 at 19. 56 kV, the ion source voltage 2 at 18. 11 kV, and the lens voltage at 7 kV. External calibration of spectra was done through the deposition of a protein standard (Protein Calibration Standard I, Bruker Daltonics) before each measurement on the same target.
MALDI-TOF spectra were processed using FlexAnalysis software (version 3. 4) (Bruker Daltonics GmbH, Bremen, Germany). Baseline subtraction using the TopHat algorithm was set with a 5% minimal baseline width. Smoothing was performed with a 1 Da width and 5 cycles. Individual spectra were normalized using the Total Ion Count (TIC) value. Peak picking was applied using the peak intensities with a signal to noise ratio of 2. Infrared spectra were obtained using a Bruker Tensor II spectrometer, and an ATR accessory with 250 μm × 250 μm diamond crystal (Specac Ltd. , Orpington, UK) operated by the OPUS 7. 5 software (Bruker, Bremen, Germany). The spectral resolution was set at 4 cm -1 , and 100 scans were used for each measurement in the range of 4,000-600 cm -1. All the sample acquisitions were performed 5 times as follows: 1 μL of plasma was spotted on the diamond crystal and left to dry at room temperature for 8 min.
Spatial variability of the DH defect The spatial variability of the PSE-like defect that occurs in cooked hams was investigated by MSI by MALDI-TOF. To determine whether the defect progressed internally within the ham, indicating a local heterogeneity, the relationship between NH molecular maps with both DHi and DHo was studied. The training set used to build the predictive model was composed of the spectral data of the DHi and DHo. Then, the data from the NH were classified using this model to determine the class to which they were closer: DHi or DHo. The model's performance was evaluated by crossvalidation accuracy, which was 87%. The model's performance can be expressed as its capability to describe The evaluation results of the predictive model are given for each spectral method, i. e.
Plasma protein fingerprint to predict the PSE-like muscle defect The second part of the study aimed to assess the capacity of protein fingerprinting by MALDI-TOF mass spectrometry and ATR-FTIR spectroscopy to predict the PSE-like muscle defect in hams. Plasma samples were chosen since it is essential not to depreciate the carcass and to develop an easy-to-use method, blood sampling being easier than muscle biopsies. In the first part of this study, the prediction capacity of both spectral approaches was assessed separately using multivariate analysis. Then, both data matrixes were analyzed using the most discriminant spectra features to determine the synergy of both of these spectral methods. The predictive model built using neural network analysis from MALDI-TOF spectra showed a classification accuracy of 84.
Sections were then incubated for 30 min at room temperature in Imm-PRESS HRP Anti-Goat Ig Polymer Detection Kit (MP-7405, Vector Laboratories, Burlingame, CA) or in antimouse EnVision+ System/HRP (K4001, Dako, Heverlee, Belgium), for goat or mouse primary antibodies, respectively. The peroxidase activity was revealed using DAB+ substrate chromogen (Dako, Heverlee, Belgium). Tissues were finally counterstained with Carazzi hematoxylin 0. 1%, then dehydrated and mounted with Eukitt medium (VWR, Leuven, Belgium). Virtual images were acquired with a fully automated digital microscopy system Nanozoomer 2. 0-HT (Hamamatsu Photonics, Shizuoka, Japan) using a 40x magnification objective (0. 23 μm/pixel) and NDP. scan software (Hamamatsu Photonics, Shizuoka, Japan). Images were visualized using Cytomine software  [30].
Clinical observations All animals lost body weight during the first 3 POW, reaching -5. 2 ± 1. 7% on POW 2 compared to body weight at surgery. From POW 4, all animals (n = 14) started to gain weight and all had recovered at least their initial body weight at POW 12 (+ 8. 3 ± 3. 5% compared to weight at surgery). At POW 26, all animals (n = 8) had gained weight compared to weight at surgery (+ 12. 1 ± 5. 0%). Signs of ocular or systemic pain and discomfort were absent throughout the study. Together, these data suggest comfort and well-being of the rabbits during the in vivo phase of the study. In eyes of both the Sham and Test groups, a similar incidence and severity of iris inflammation (graded mild to severe), aqueous flare (graded mild to moderate), fibrin in the anterior chamber (incidence only, severity not graded), cornea cloudiness (graded minimal to mild) and fluorescein staining (graded slight) were observed.
However, no fibrosis nor dense connective tissue development were observed within any implant at any time point. The only instance of collagen fibers within pores (including Type III collagen-positive fibers) was in the case of contact between the implant and the cornea. The cornea-implant contact was assumed to be favored by the narrow iridocorneal angle in rabbits (~12. 5°vs 35-45°in the human eye). Endothelial cell density changes were not measured. No blood nor lymphatic neovessels were in evidence within the porous structures. The pore colonization was deemed to be stable over the time interval between 1 month and 6 months, following suprachoroidal implantation of the MINIject device. No mitosis was observed within the porous structures at any post-operative timepoint. Together, these data suggest that porous structure colonization results from cell migration from surrounding reactive tissues into the porous structure of the implant, and not by any cell proliferation within the implant itself.
Discussion Our study provides data on the biocompatibility and tolerability of the novel MINIject MIGS device following implantation in the suprachoroidal space of rabbits. No biocompatibility issue was identified as being induced by the MINIject device after implantation for 6 months into the suprachoroidal space in the rabbit eye. Minimal encapsulation was seen around the implant and was assessed to become stable within 4 weeks after implantation. Implant biointegration, characterized by the colonization of its porous structure by cells of surrounding tissues, was identified and was also assessed to become stable within a short time following implantation (4 POW).
Conclusions The results of these two in vivo pre-clinical studies have demonstrated that MINIject (a novel MIGS device made of porous silicone) is biocompatible and very welltolerated in ocular tissues when placed into the suprachoroidal space of rabbits. There is very little fibrotic encapsulation surrounding the implant. Biointegration is present and may prevent significant fibrous encapsulation, thus preserving the permeability of the surrounding tissues. Pore colonization, once established, is stable and primarily cellular, supporting the assumption that tissue colonization does not impair fluid drainage through the porous matrix over time. In conclusion, these data strongly suggest that the MINIject implant may provide a long-term ability to enhance aqueous outflow.
Statistical Analysis All in vitro experiments were performed ≥3 independent times, as indicated in the figure captions, in duplicate, triplicate, or quadruplicate wells. The independent number of animals in each group is indicated in the figure legends. Data are displayed as mean of independent experiments/independent animal samples±SEM if not otherwise specified in the figure legend. Statistical analysis was carried out with the GraphPad Prism 6 software (GraphPad Prism Software Inc, San Diego, CA). For comparison of 2 groups, unpaired 2-tailed Student t test was applied, and for analysis of ≥3 groups, 1-way ANOVA with Turkey and 2-way ANOVA with Tukey multiple-comparisons test were performed if not otherwise specified in the figure legend. In all cases, a value of P≤0. 05 was considered statistically significant.
ORIGINAL RESEARCH ARTICLE fibrotic responses in cardiac fibroblasts, proliferation of HCFs was studied after incubation with 480 individual compounds, selected from a database comprising 150 000 natural products for a maximum of chemical diversity with the OptiSim algorithm (Figure  1A  and 1B). Applying a selection threshold of fibroblast proliferation inhibition fold change ≥75%, we identified 15 candidates, of which 5 inhibited proliferation rates in a dose-dependent manner (Figure  1B  and 1C). Next, we excluded cell death to be involved in the observed decrease in proliferation triggered by these compounds (bufalin, gitoxigenin, lycorine, anisomycin, and geldanamycin). Therefore, HCFs were treated with respective compounds using the effective doses and subjected to fluorescence-activated cell sorter analysis after annexin-7AAD staining (Figure  1D ).
To further elaborate on fibroblast-specific actions of bufalin and lycorine, we determined the cell size of neonatal rat cardiomyocytes stimulated with Ang II on treatment with the 2 lead drug candidates. Neither bufalin nor lycorine counteracted the hypertrophic growth of cardiomyocytes in vitro stimulated by Ang II (Figure IB and IC in the online-only Data Supplement). Of note, lycorine but not bufalin exerted slight inhibitory effects on proliferation of the rat renal fibroblast cell line NRK49F (Figure ID in the online-only Data Supplement). In contrast, bufalin in particular inhibited proliferation of primary human pulmonary fibroblasts (Figure IE in the online-only Data Supplement). These results might suggest a potential therapeutic implication of the substances not only in cardiac but also in renal or pulmonary fibrotic diseases, respectively.
Bufalin and Lycorine Prevent Fibrosis and Preserve Cardiac Function in Ang II-Induced Cardiac Remodeling To verify whether the identified antifibrotic substances prevent fibrosis development at early stages also in vivo, C57BL/6N mice were infused with Ang II by subcutaneously implanted minipumps for 2 weeks. The natural substances (dissolved in dimethyl sulfoxide) or the solvent alone (as control) was injected intraperitoneally every other day until the end point, beginning 1 day after the start of Ang II infusion. Histological sections of the heart were studied for fibrosis development, and cardiac function was assessed both echocardiographically and hemodynamically. A schematic representation of the preventive in vivo study is depicted in Figure  2A. Ang II infusion led to a significant decrease in body weight (Figure IF in the online-only Data Supplement) which linked with increased ratios of heart to body weight in animals infused with the solvent only (controls); however, bufalin or lycorine did not significantly prevent this effect (Figure  2B ).
ORIGINAL RESEARCH ARTICLE indicates true improvement of tissue function, making pseudonormalization unlikely (Figure  2H ). The preventive effect of lycorine on MPI and of bufalin on E/A ratio was of borderline significance (Figure  2D  through 2G). Hemodynamic pressure-volume measurements were performed to assess LV compliance. Treatment with bufalin or lycorine completely counteracted the development of passive stiffness of the LV caused by the Ang II infusion, as evidenced by a reduction of the end-diastolic pressure-volume relationship (Figure  2I ). In line with the heart weight data (Figure  2B ), cardiac mass measured by echocardiography was slightly increased but unaffected by bufalin or lycorine in the Ang II-treated groups (Figure  2J ). Bufalin and lycorine were detectable in cardiac tissue (and plasma) of mice, confirming their uptake into the heart on systemic delivery (Figure IID and IIE in the online-only Data Supplement).
Antifibrotic effects of bufalin on α-SMA expression of primary HCFs are significantly disturbed on overexpression of miR-671-5p, reflected by elevated α-SMA expression (Figure  5D ), suggesting a role for miR-671-5p in the antifibrotic efficacy of bufalin. Because of an intronic localization of miR-671-5p, expression of its host gene chondroitin polymerizing factor (CHPF) was additionally determined in primary HCFs after treatment with the lead compounds. Expression levels of CHPF, however, did not change consistently in primary HCFs on treatment with the identified molecules (Figure VIIB in the online-only Data Supplement), suggesting that the substances do not directly drive transcription of the miR-671-5p host gene CHPF. Consistently, increased miR-671-5p expression could be observed in fibrotic conditions in vivo.
ORIGINAL RESEARCH ARTICLE online-only Data Supplement). Repression of SEPP1 by miRNA-671-5p would therefore support the detrimental activity of this miRNA. To validate the bioinformatic prediction via TargetScanHuman, we cloned the 3′ untranslated region of SEPP1 downstream of the firefly luciferase gene and found the normalized luciferase activity to be markedly reduced on cotransfection of the construct with miR-671-5p mimic compared with the miR-mimic control (Figure  6B ). To prove that SEPP1 is a target of miR-671-5p in primary HCFs, SEPP1 levels on overexpression of miR-671-5p were monitored. Levels of SEPP1 were prominently and significantly decreased in primary HCFs after overexpression of miR-671-5p (Figure  6C ). These data validate SEPP1 as a target of miR-671-5p in primary HCFs.
Acknowledgments The authors thank the  Hannover Biomedical Research School  and the  Integrated Research and Treatment Center Transplantation, Hannover Medical School, Germany , for financial support to  L. Grote-Levi  and  K. Bock. They thank  Ellen T. Roche ,  Department of Mechanical Engineering and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge , for generous lending of the Millar catheter for the rat study.
A second questionnaire covered the postlockdown period and was sent between May 5, 2020 and June 15, 2020. The present study used the data from the first self-administered questionnaire, which included questions on socio-demographics, household size and composition, SARS-CoV2 diagnosis, a detailed description of the subject's symptoms in the 2 weeks before the questionnaire, comorbidities, healthcare use and treatment, employment, daily life, child care, alcohol, tobacco and cannabis use, social and sexual life, preventive measures, risk perception and beliefs. Additional specific socio-demographic and clinical characteristics were extracted from original cohort databases. Symptoms were reported if they had been present at least once in the last 14 days. If a symptom had been, but was no longer present when the questionnaire was completed, the duration was noted on a scale (less than 1 day, one to 3 days, four to 7 days, eight to 14 days, > 14 days).
Estimates of unweighted and weighted cumulative incidences on days 15 (March 30, 2020), 30 (April 14, 2020) and 45 (April 29, 2020) of lockdown were obtained as one minus the estimated probability of survival free of CLS at that time. To account for potential heterogeneity between the cohorts, left-truncation and censorship in the data, factors associated with the occurrence of CLS were identified using unweighted data and delayed-entry Cox models with stratification on the source cohort. The start of the at-risk period was defined according to the calendar day for each participant and survival time was calculated as the time between that day and the day the questionnaire was filled-out in case of no symptom or the day the first symptoms were reported in CLS cases. Multivariable analysis was performed including all factors associated with CLS cases on univariable analysis.
Acknowledgments The authors warmly thank all the volunteers of the CONSTANCES,  E3N-E4N , and  NutriNet-Santé  cohorts. We thank the staff of the  CONSTANCES ,  E3N-E4N  and  NutriNet-Santé  cohorts that have worked with dedication and engagement to collect and manage the data used for this study and to ensure continuing communication with the cohort participants. We thank  Mrs. Dale Roche-Leclerc  for her help in editing the manuscript. The SAPRIS study group. Nathalie Bajos  (co-Principal investigator),  Fabrice Carrat  (co-Principal investigator),  Pierre-Yves Ancel ,  Marie-Aline Charles ,  Florence Jusot ,  Claude Martin ,  Laurence Meyer ,  Ariane Pailhé ,  Gianluca Severi ,  Alexis Spire ,  Mathilde Touvier ,  Marie Zins. Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center -University of Paris (CRESS), Bobigny, France.
Here we established the proof of concept of the use of MS/MS for the rapid proteotyping of SARS-CoV-2 from clinical samples. We recently published a dataset from a shotgun LC-MS/MS experiment performed with SARS-CoV-2 infected cells and proposed a list of specific viral peptides that could be used for the development of targeted approaches  (23). Interestingly, we observed that some SARS-CoV-2 specific peptides eluted from the LC column at narrow windows of retention time. Here, we used LC-MS/MS with an Orbitrap instrument (Q Exactive HF) for analyzing the peptidome from nasal swabs spiked with different quantities of viral material. By using a short LC gradient focusing on the region of interest identified in our previous study, we tested the detection of the virus in samples containing different quantities of viral peptides, as well as COVID-19 clinical samples, paving the way for the development of time-efficient viral diagnostic tests based on an alternative platform.
Cell culture and Virus Vero E6 (ATCC, CLR-1586) cells were cultured at 37°C in 9% CO2 in Dulbecco's modified Eagle's medium (DMEM, Gibco, ThemoFisher) supplemented with 5% fetal calf serum (FCS) and 0. 5% penicillin-streptomycin. The SARS-CoV-2 strains 2019-nCoV/Italy-INMI1 (Genbank MT066156) was provided by the Lazzaro Spallanzani National Institute of Infectious Diseases (Rome, Italy) via the EVAg network (European Virus Archive goes global). SARS-CoV-2 stocks used in the experiments had undergone two passages on Vero E6 cells and were stored at -80°C. Virus titer was 7. 25x10 5 plaque forming units (PFU)/mL, as determined by standard plaque assay (three dilutions in duplicates). All experiments entailing live SARS-CoV-2 were performed in our biosafety level 3 facility and strictly followed its approved standard operating procedures.