dataesr/scientific-paragraphs-categorization huggingface dataset:
Background/aims To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. Methods A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. Results At baseline, mean VA in HRVO (53. 8) was similar to CRVO (51. 9; p=0. 40) but lower than BRVO (59. 4; p=0. 009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months.
Clinical science treatment were made at the discretion of the treating physician. The type of RVO (BRVO, HRVO or CRVO) was categorised by the treating physician at enrolment. A baseline visit captured demographic data when the first injection was administered. The number of letters read on a logarithm of the minimum angle of resolution VA chart (best of uncorrected, corrected or pinhole), central subfield thickness (CST in µm), the presence of cystoid macular oedema (CMO, active or inactive as judged by the treating physician), any treatments given, other procedures performed, and adverse events were recorded at baseline and follow-up visits.
Statistical analysis Observations began at the first injection and continued until the 12 month visit (365±30 days). Baseline data were summarised using the mean, SD, median, first and third quartiles (Q1, Q3) and percentages where appropriate. Comparison between cases and controls used t-tests, Wilcoxon rank-sum tests, χ 2 tests and Fisher's exact tests where appropriate. Crude visual and anatomic outcomes used the last observation carried forward for non-completers. Outcomes were adjusted for baseline differences using analysis of covariance (ANCOVA). Visits were censored after any steroid injection to examine outcomes while only on VEGF inhibitors. Generalised additive mixed effects models were used to plot longitudinal changes in VA and CST for each type of RVO while only on VEGF inhibitors.
We reported the number of injections and visits for completers but also used generalised Poisson mixed models to compare groups incorporating all eyes up to completion, non-completion, or receipt of an intravitreal steroid. Kaplan-Meier survival curves were generated for event-based outcomes. Analysis was performed in R V. 4. 1. 0 ( cran. r-project. org) utilising the lme4 (1. 1-27. 1) and mgcv (V. 1. 8-35) packages for linear and generalised additive mixed effects models respectively. 15 The survival (3. 2-11) package was used to generate the Kaplan-Meier estimates. 15 A p<0. 05 was considered statistically significant.
DISCUSSION This analysis using the FRB! observational database found that HRVO was a distinct clinical entity at baseline and in response to VEGF inhibitors compared with BRVO and CRVO. VA at baseline in HRVO eyes was worse than BRVO and closer to CRVO while macular thickness at baseline placed HRVO between BRVO and CRVO eyes to concur with previous reports. 5 Once treatment was underway, the mean VA and CST in HRVO almost mirrored BRVO through 12 months. The mean change in VA over 12 months, the primary outcome, was significantly higher in eyes with HRVO (+16. 4 letters) than with BRVO (+11. 4 letters; p=0. 006) and with CRVO (+8. 5 letters; p<0. 001). Mean change in CST was largest in CRVO, closely followed by HRVO which was significantly greater than BRVO eyes. Treatment burden was similar across all forms of RVO at around eight injections in this realworld study.
Clinical science Randomisation aims to minimise selection bias so that any difference in outcome between groups can be explained only by the treatment. There is potential for confounding when stratification based on HRVO is not done and disproportionate contributions are made by HRVO to study groups receiving different treatments. For example, randomisation distributed 24 HRVO eyes to the aflibercept group (13%) and 31 eyes to the bevacizumab group (17%) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) study. 23 nother comparative study had 15% HRVO in a ranibizumab group and 19% in a bevacizumab group when it compared outcomes in CRVO. 12 here are some limitations inherent with the observational design of this study. The FRB! registry does not use reading centres and relies on the diagnosis and consistency of the treating physicians that are obliged to include least 85% of their relevant patients and finalise data entry in over 95% of visits to fulfil audit requirements.
Probands with MAC and no genetic diagnosis We selected 78 patients with a clinical diagnosis belonging to the MAC spectrum and no familial history of ocular defects. They were previously explored by the mean of a HTS panel of 119 genes of ocular development (Supplementary Data 1) without any disease-causing variant identi ed. DNA was extracted from blood using the MagnaPure system (Roche Applied Science, Germany), except for three individuals whose DNA was extracted from other tissues (two from amniotic liquid, one from muscle fetal tissue). Capture probes were designed with SureDesign (Agilent, USA). A library of all coding exons and intronexon boundaries was prepared using the SureSelect XT HS and XT Low Input Enzymatic Fragmentation Kit and the SureSelect XT HS Target Enrichment System for Illumina Paired-End Multiplexed Sequencing Library (Agilent, USA) following the manufacturer's instructions.
github. io/picard/) respectively. Variant Calling step used three different variant callers in parallel: Mutect2 16 , VarDict  17  and FreeBayes  18. The pipeline was able to detect a variant as low as 4% of allelic frequency at 100-fold depth in a previous test performed in our laboratory with known mosaic variants (data not shown). The standardization of VCF les follows the VCF 4. 3 speci cations, which allows secondary fusion of cooccurring variants and haplotype normalization and the production of a unique variant calling le (VCF) by sample. Annotation were made using VEP tool (Ensembl). We analysed annotated VCFs without lters on allelic frequency. Of note, we analysed the parents' annotated VCF with a focus on the offspring's pathogenic variant to avoid unwanted secondary ndings. To be sure our pipeline did not miss any parental mosaic, their binary alignment map (BAM) les were visualized at offspring's variant position using Integrative Genomics Viewer (IGV).
Parental segregation study of apparently de novo pathogenic variants We retrieved 41 probands with disease-causing variants in ocular development genes previously identi ed in our laboratory (PAX6, SOX2, RARB, OTX2, PAX2, PRSS56, CHD7, TFAP2A, RAX, GJA8, BMP4, CRYAB, PITX2 and ITPR1) (genotypes are detailed in Supplementary Data 3). They displayed various ocular defects belonging to the MAC or ASD spectrum (Supplementary Data 3). For all probands, parental segregation was previously performed on both parents using direct sequencing and did not nd offspring's disease-causing variants. Parents were all asymptomatic after ophthalmologic examination. A recurrence in a proband's sibling was noted in only two families (SG040829, SG110088). Resequencing of the 80 parents revealed two parental somatogonadal mosaicisms (Fig.
| Cell culture, transfection and treatments Human MPM cell lines MSTO-211H (RRID:CVCL_1430), NCI-H2452 (RRID:CVCL_1553), NCI-H28 (RRID:CVCL_1555), NCI-H2052 (RRID:CVCL_1518) from the American Tissue Culture Collection (ATCC) and T-47D (RRID:CVCL_0553), a generous gift from Pr Le Romancer (Cancer Research Center, Lyon, France), were maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum, 10 mM L-glutamine, streptavidin/penicillin (100 μg/mL) and kanamycin (100 μg/mL). All human cell lines have been authenticated using short tandem repeat profiling within the last 3 years. All experiments were performed with mycoplasma-free cells. Cells were transfected with siRNA or plasmid DNA using JetPRIME (Polyplus-transfection), as previously reported 3 (Table  S1 ). Exogenous AREG (20 ng/mL) was added to the cell supernatant 24 hours following the cell transfection or treated with phorbol 12-myristate 13-acetate (PMA, 25 ng/mL) for 30 minutes to 3 hours.
| DISCUSSION AREG overexpression was previously observed in MPM cells, compared to normal pleural mesothelial cells,  18  but we here provide data reinforcing that tumor AREG could also be used as a prognostic marker for MPM patients. We confirmed that 64. 3% of MPM patients highly expressed tumor AREG and that this expression is more frequent in patients with the epithelioid histological subtype, such patients being known to have a better prognosis with higher chemo-sensitivity. F I G U R E 6 SDC1 shedding activity in malignant pleural mesothelioma cell lines. Expression of SDC1 mRNA in MPM cell lines and T47D: *P <. 05, using an ANOVA test followed by a Tukey test (n = 4) (A). SDC1 was visualized by immunocytochemistry after staining of the nuclei with DAPI. The scale bar represents 50 μm (B).
Funding information The  Bio-MAPS study  was sponsored by the  Intergroupe Francophone de Cancérologie Thoracique (IFCT) , and funded by an unrestricted research grant from  ROCHE-France , research grants from  ROCHE-France  (2013) and from the  Fond de Recherche en Santé Respiratoire (FRSR ,  2012 ) to  Guénaëlle Levallet , a research grant "APRI" from  Caen University Hospital  for  S. Brosseau  ( 2014 ), and a research grant from the  Normandie League  against cancer for G. Zalcman (2012).
Study Population: Inclusion and Exclusion Criteria All consecutive children with BA managed in the respective centers were enrolled if they fulfilled the following criteria: (i) <3 years of age at assessment for LT, and (ii) assessed and transplanted within the contributing centers between 1 January 2016 and 31 December 2020. For those who had been transplanted, only those with a minimum of 3 months follow-up after LT were included at the time of selection and data gathering. As the study was an "intent-to-LT" analysis, the endpoints were "transplant" or "death (while waiting for LT)". Patients who were still waiting on the list at the study closure date were excluded, as well as those who were removed from the list during the study period because of being "too-well" or clinically improving to the point that LT was not recommended.
Data for Analysis All data were retrospective and retrieved from the patients' medical and operational records. This was performed once and only for the purpose of the analyses by one of the co-authors of the caring center. Data and information were collected about: (1) The history of prematurity, comorbidities and associated malformations, poly-malformative atresia or not. (2)  The type of initial surgery for BA (no-surgery, laparotomy or Kasai procedure) and the type of center for Kasai ((a) non-liver-expert center (i. e. , no multidisciplinary pediatric liver service), (b) liver-expert center (i. e. , multidisciplinary pediatric liver service available but no transplant service) and (c) pediatric LT center (LTC including multidisciplinary pediatric liver services). (3) Age at initial operation, age at assessment and age at registration on the transplant list.
Prolonged waiting time is also associated with clinical deterioration, hospital boundness and/or LT under urgent conditions-all conditions associated with increased (although preventable) peri-transplant morbidity and mortality. Use of PELD exception or priority status for biliary atresia patients registered on the waiting list before age 3 years, according to the type of allocation rules and types of organ used. Transplant data from 7 centers. 1-Proportion of transplants performed under PELD exception or priority status (red line) (values in % in each transplant), and 2-number of transplants and graft types used: whole livers (black), split livers (green) and living donor grafts (yellow). Centers (defined as in Figure  1 ) are aligned left to right according to their affiliation to one of 3 allocation systems that differ about allocation rules for small children (see legend on the bottom).
Figure3. Use of PELD exception or priority status for biliary atresia patients registered on the waiting list before age 3 years, according to the type of allocation rules and types of organ used. Transplant data from 7 centers. 1-Proportion of transplants performed under PELD exception or priority status (red line) (values in % in each transplant), and 2-number of transplants and graft types used: whole livers (black), split livers (green) and living donor grafts (yellow). Centers (defined as in Figure1) are aligned left to right according to their affiliation to one of 3 allocation systems that differ about allocation rules for small children (see legend on the bottom).
| Demographic, clinical, and medical data collection For each selected patient, the following data had been previously registered in a declared database (RMR004-061120) during their hospital stage: sex, age, comorbidities, immunocompromised state, date of symptoms onset, new early warning score (NEWS) graded at the time of hospital admission,  11  computerized tomography chest scan results (CT-chest scan), drugs prescription, and further need for ICU admission and in-hospital mortality. Demographic and clinical characteristics of study patients are depicted in Table  1.
| Statistical analyses Quantitative variables expressed as median [range] were compared using the Mann-Whitney U test. Qualitative variables expressed as percentages were compared using Fischer's exact test or Pearson's χ 2 if applicable. When linear regression was performed, slopes were compared using Spearman's test. When receiver operating characteristic (ROC) curve analysis was performed, area under ROC curve, standard error, and p value were calculated using the trapezoid rule, the Hanley method, and Z ratio, respectively. A p < 0. 05 was considered statistically significant. Statistical analyses were performed using GraphPad Prism 8 (GraphPad) and SAS version 9. 4 (SAS Institute Inc. ).
From this research biobank samples (n = 4704 sampled patients), we retrospectively selected samples taken from adult patients (i) hospitalized in medicine wards for COVID-19 (n = 1116); (ii) with a time delay less than 9 days between sample collection and onset of COVID-19 symptoms (n = 183); (iii) with full clinical data available from a registered clinical data bank (Reims University Hospital GDPR number RMR004-061120) elaborated for an internal purpose between March 1, 2020 and March 31, 2021 and focusing on COVID-19 adult patients (n = 143). Patients who required palliative care or hospitalized directly in ICU were excluded from the study. Finally, only 43 COVID-19 adult patients with available frozen EDTA-plasma samples and with full registered clinical data were included in this retrospective investigation.
Overall, our findings indicated that early peripheral blood IFN-β levels might be a relevant predictive marker of further need for an ICU admission in COVID-19 adult patients, specifically when clinical score (NEWS) was graded as upper than 5 at hospital admission. AUTHOR CONTRIBUTIONS Andreoletti Laurent, N'Guyen Yohan, and Berri Fatma designed the study. Andreoletti Laurent, Berri Fatma, and N'Guyen Yohan wrote the manuscript. Andreoletti Laurent, Pham Bach-Nga, and N'Guyen Yohan established the research biobank, the clinical data bank, and supervised the data collection. Berri Fatma and N'Guyen Yohan analyzed the data and designed the table and the figures. Callon Domitille helped for data collection. Berri Fatma, N'Guyen Yohan, Andreoletti Laurent, Callon Domitille, Labreil Anne-Laure, Glenet Marie, Heng Laetitia, Bani-Sadr Firouze, and Pham Bach-Nga provided valuable input to interpretation of the data and critically reviewed the manuscript.
ACKNOWLEDGMENTS We acknowledge  Dr. Nicolas Richet  ( URCA, Université de Reims Champagne-Ardenne, Plateau Technique MOBICYTE ) for performing the Droplet Digital PCR analysis. We are indebted to Pr. Christine Hoeffel ,  Dr Clément Lier ,  Dr Coralie Barbe ,  Cécile Grasset , and  Cécile Reppel  for their help in the preparation of this manuscript. This work was supported by a research grant  URCA-2020-EA4684  dedicated to research teams from the  University of Reims Champagne-Ardenne. This work was supported by a research grant  URCA-2020-EA4684  dedicated to research teams from the  University of Reims Champagne-Ardenne.
Cloning of cDNAs encoding octanoyltransferases from H. annuus The Arabidopsis plastidial octanoyltransferase (AtLIP2p) protein sequence, encoded by the AT4G31050. 1 gene and retrieved from public databases, was used to search for sunflower homologues in the sunflower genome database (Sunflower genome portal Heliagene -https:// www. heliagene. org/: Badouin et al. , 2017). Two cDNA molecules were selected, HaLIP2p1 and HaLIP2p2, and specific PCR primers were designed to amplify both these genes, including their ATG and STOP codons (Table  S1 : primers were synthesized by Eurofins MWG Operon, Germany). The PCR fragments were purified and cloned into the pMBL-T Easy vector (Canvax, Spain), and the nucleotide sequences were confirmed by sequencing (Secugen, Spain). The confirmed sequences were deposited in GenBank under the accession numbers MT610110 (HaLIP2p1) and MT610111 (HaLIP2p2).
Protein sequence analysis The protein sequences derived from the HaLIP2p1 and HaLIP2p2 genes were obtained using the BLASTp program  (Camacho et al. , 2009). These were aligned with homologous sequences and a phylogenetic analysis was performed using ClustalX v. 2. 0. 10 software  (Larkin et al. , 2007)  and MEGA6 software  (Tamura et al. , 2013). An in silico analysis of protein localization was carried out using the DeePLoc  (Almagro Almagro Armenteros et al. , 2017) , TargetP V1. 1  (Emanuelsson et al. , 2007) , iPSORT  (Bannai et al. , 2002)  and Predotar  (Small et al. , 2004)  applications. ClustalX v. 2. 0. 10 and BioEdit  (Hall, 1999)  were used to study evolutionarily conserved residues through their alignment with homologous proteins from different phylogenetic groups: Arabidopsis thaliana, Ricinus communis, Oryza sativa and Amborella trichopoda.
Modeling the three-dimensional structure of HaLIP2p and molecular docking Homology modeling was performed using the Swiss Model server  (Schwede et al. , 2003 ; http://swissmodel. expasy. org/) and the M. tuberculosis LIPB X-ray structure as a template (MtLIPB:  Ma et al. , 2006). The UCSF Chimera program  (Pettersen et al. , 2004)  was used to visualize the model. Molecular docking was performed using the SwissDock server  (Grosdidier et al. , 2011a and 2011b)  with octanoic acid as a substrate (ZINC01530416). The docking model was then visualized and analyzed with the UCSF Chimera program.
Real-time quantitative PCR (RT-qPCR) The expression of HaLIP2p1 and HaLIP2p2 was analyzed by RT-qPCR using sunflower cDNAs from developing seeds (16, 20, 25 and 30 days after anthesis -DAA), roots, stems, cotyledons and leaves. A CFX96 TM real-time PCR detection system (Bio-Rad) was used to perform the reactions with SYBR Green I (QuantiTec SYBR Green PCR Kit: Qiagen, Crawley, UK) and specific primer pairs (HaLIP2p1qpcr-F/HaL-IP2p1qpcr-R for HaLIP2p1 and HaLIP2p2qpcr-F/HaLIP2p2qpcr-R for HaLIP2p2: Table  S1 ) over 40 PCR cycles: 94 • C for 30 s, 57 • C for 30 s and 72 • C for 1 min. The Livak 2 ΔΔCt method (Livak and Schmittgen, 2001) were used to calculate their expression normalized to the sunflower housekeeping gene actin (HaACT, GenBank Accession No. FJ487620, HaActin-qpcr-F4 and HaActin-qpcr-R4 primers: Table  S1 ).
(2019). LC-electrospray ionization (ESI)-HRMS2 analysis was performed by coupling the LC system to a hybrid QToF high definition mass spectrometer (Agilent 6538: Agilent Technologies) equipped with a dual ESI source. The parameters were controlled using MassHunter B. 07 software and the chromatogram was built as described in Martins-Noguerol et al. (  2020 ). The peaks were annotated using two different databases: lipid Match  (Koelmel et al. , 2017)  and lipid Blast  (Kind et al. , 2013).
Statistical analysis Statistical analysis was carried out using IBM SPSS v. 24. 0 software (IBM Corp. , Armonk, N. Y. , USA). The data were tested for normality (Kolmogorov-Smirnov test) and homogeneity of variance (Levene test), and a one-way analysis of variance (ANOVA) was performed determining the significant differences with a Tukey test. The data from the lipidomic analysis were analyzed using Metaboanalyst v4. 0  (Chong et al. , 2019)  and performing a multivariate analysis. A principal component analysis (PCA) was performed to study the differences in the lipid profiles among the different genotypes. Finally, an agglomerative analysis was carried out to obtain hierarchical clusters, which were represented together with heatmaps in which the cells represent the concentration of each lipid species.
Cloning and sequence analysis of two lipoyl octanoyltransferases from sunflower Two coding sequences were identified within the sunflower genome database (Heliagene,  Badouin et al. , 2017)  based on their homology to the Arabidopsis LIP2p gene (At4g31050. 1), located on chromosome (HaLIP2p1; HanXRQChr09g0268371) and chromosome 5 (HaLIP2p2; HanXRQChr05g0141551). Using these sequences, PCR products of bp (HaLIP2p1) and 873 bp (HaLIP2p2) were amplified from 25 DAA sunflower seed cDNA, and the protein sequences encoded by these cDNAs contained 283 (HaLIP2p1) and 290 (HaLIP2p2) residues. When these genes were launched into location predictors (DeePLoc: Almagro Almagro Armenteros et al. , 2017) they were both clearly classified as plastidial proteins (Figs. S1  and S2 ). The plastid transit peptide was located in the N-terminus of the proteins, Arg52 and Arg46, representing the first residues in the mature HaLIP2p1 and HaLIP2p2 proteins, respectively (Fig.
As we hypothesized for bacteria, a potential competition between KAS I and LIP2p proteins is present within plastids. HaLIP2p1 overexpression could produce an excess of octanoyltransferase activity, leading to a depletion of octanoyl-ACP in Arabidopsis plastids. Accordingly, a reduced availability of octanoyl-ACP for KAS I activity will lead to a decrease in fatty acid synthesis. Previously, Arabidopsis mutants with low KAS I and KAS III activities were seen to have reduced fatty acids synthesis  (Wu and Xue, 2010; Takami et al. , 2010). In order to clarify the role of LIP2p during fatty acid synthesis, a relatively complete lipidomics analysis in transgenic seeds was carried out. This study revealed different lipid profiles in both transgenic and WT seeds. The PCA analysis separated the data from both genotypes indicating that the overexpression of HaLIP2p1 had consequences on lipid biosynthesis.
Acknowledgements This work was supported by  Spanish State Research Agency  Projects  AGL 2017-83449-R  and  PID 2020-113134RBI00 , and the  CSIC  Project  I-LINK1186. The authors also wish to thank the  Hauts-de-France Region  and the  European Regional Development Fund (ERDF)   2014/2020  for their funding of this work.
Statistical Analysis Analyses were performed using the Statistical Package for the Social Studies software version 20. Quantitative variables were expressed as mean (± standard deviation, SD) and qualitative variables as count (percentage). Progression-free survival was defined as the number of months from the diagnosis to the identification of locally recurrent or metastatic disease in the lymph nodes or distant organs. Death was considered as melanoma-related in patients for whom the melanoma had progressed. A univariate analysis was performed to investigate the association between histological regression characteristics, inflammatory infiltrate status, and prognosis, using a chisquared 2 test. A P value ⩽0. 05 was considered as significant.