dataesr/scientific-paragraphs-categorization huggingface dataset:
SK laboratory is supported by the  "Université Grenoble Alpes "  ANR-15-IDEX-02 LIFE  and SYMER programs. Additional support to the  SK laboratory came  from:  Fondation   ARC "Canc'air" project  ( RAC16042CLA ),  Plan Cancer  ( CH7-INS15B66 ) and  Plan Cancer  ( ASC16012CSA ) and  ANR   Episperm3 program. The EDEN cohort has been funded by the  Foundation for Medical Research (FRM) ,  National Agency for Research (ANR) ,  National Institute for Research in Public Health (IRESP: TGIR cohorte santé 2008 program ),  French Ministry of Health (DGS) ,  French Ministry of Research, Inserm Bone and Joint Diseases National Research (PRO-A)  and  Human Nutrition National Research Programs, Paris-Sud University, Nestlé ,  French National Institute for Population Health Surveillance (InVS) ,  French National Institute for Health Education (INPES) , the  European Union   FP7  programs (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects),  Diabetes National Research Program  (through a collaboration with the  French Association of Diabetic Patients (AFD)) ,  French Agency for Environmental Health Safety (now ANSES) ,  Mutuelle Générale de l'Education Nationale (MGEN) ,  French National Agency for Food Security , and the French-speaking association for the study of diabetes and metabolism (ALFEDIAM).
Funding: This work was supported by the  French National Cancer Institute (INCa)  and the  French Institute for Public Health Research (IReSP)  ( INCa_13641 ), the  French Agency for National Research  ( ANR-18-CE36-0005 ) and  AVIESAN (Alliance nationale pour les sciences de la vie et de la santé , grant number  ISP09_2014 ). DNA methylation measurements were obtained thanks to grants from the  Fondation de France  (n°  2012-00031593  and  2012-00031617 ) and the  French Agency for National Research  ( ANR-13-CESA-0011 ).
The DNA was sent to the Max Planck Institute genome sequencing centre for library construction (Cologne, Germany) and six SMRT cells were sequenced on an RSII instrument using P6-C4 chemistry, producing over 7. 46 Gb of long-read sequence data with an average insert size of ca. 15 kb. The raw reads were trimmed, self-corrected and assembled using the Canu pipeline v1. 0  12  with the following parameters: genomeSize = 110m, minOverlapLength = 1,000, utgGraphErrorRate = 0. 020, utgRepeatErrorRate = 0. 020. Two successive rounds of genome polishing were performed with Quiver (https://github. com/ PacificBiosciences/GenomicConsensus (date last accessed 12 April 2019)) and a final correction was performed by mapping the Illumina genomic DNA libraries to the assembly using the CLC Genomics Workbench (95% similarity over 95% of the read length) and calling bases on a majority-rule basis with areas of zero coverage filled from the PacBio reference.
Illumina RNA-Seq Approximately 50 ml of log-phase C. paradoxa culture was centrifuged for 2 min and the cell pellet was ground in liquid nitrogen prior to extraction using TRIzol (Thermo Fisher Scientific) per the manufacturer's protocol. Approximately 100 ng of total RNA was used to prepare an Illumina RNA-Seq library with the RNA Sample prep kit v2 (Illumina, Inc. ) and sequenced on a MiSeq instrument in 2 Â250 bp paired-end mode using a 500-cycle MiSeq reagent kit V2 (Illumina, Inc. ). These reads were quality and adapter trimmed using the CLC Genomics Workbench, assembled to transcripts using Trinity  13  in both a de novo and genome-guided manner, and clustered at 95% sequence similarity using CD-HIT. 14 Evidence of long overlapping ORFs on these transcripts was found by translating with EMBOSS.
Illumina genome data Approximately 50 ml of log-phase C. paradoxa culture was centrifuged for 2 min and the cell pellet was extracted using the Qiagen DNeasy Plant DNA kit. Two aliquots of ca. $200 ng of genomic DNA were each sheared using a Covaris ultrasonicator (Covaris, Inc. , Woburn, MA) to 500 and 800 bp, respectively, and used to construct two individual sequencing libraries using the TruSeq Nano DNA Sample prep kit (Illumina, Inc. ) that were then sequenced on a MiSeq instrument in 2Â300 bp paired-end mode using a 600-cycle MiSeq reagent kit v3 (Illumina, Inc. ). Two sequencing runs were performed: one with the 500 and 800 bp inserts multiplexed, and another with the 500 bp insert alone. In total we produced 109 million reads totalling 33. 59 Gb of C. paradoxa genomic DNA. Reads were quality and adapter trimmed using the CLC Genomics Workbench (Qiagen).
Analysis of repeat content We compared the repeat content of the C. paradoxa genome against those in red and green algal genomes. To minimize potential biases of misassembled repetitive regions, we focussed only on available genome assemblies that comprise highly contiguous sequences or at chromosomal resolution: three red algae (Cyanidioschyzon merolae  16  [NCBI BioProject PRJNA10792], Gracilariopsis chorda  17  [PRJNA361418], and Porphyra umbilicalis 18 v1. 5 [PRJNA234409]), and three green algae (the prasinophytes, Micromonas commoda 19 RCC299 [PRJNA15676] and Ostreococcus lucimarinus 20 CCE9901 [PRJNA13044], and Chlamydomonas reinhardtii 21 v5. 5 [PRJNA12260]). For each genome assembly, a de novo repeat library was first derived using RepeatModeler v1. 0. 11 (http://repeatmasker. org/RepeatModeler (date last accessed 12 April 2019)) at default setting.
Gene prediction The RNA-Seq reads were mapped to genome contigs using STAR  22  and the resulting. bam file was used in the BRAKER1 pipeline  23  to ultimately train Augustus  24  in predicting genes across the C. paradoxa genome. Augustus predicted 25,831 genes encoded on the C. paradoxa contigs. Each translated protein sequence was used in a BLASTp query against the NCBI 'nr' database (E-val =1Â10 À5 ) to assign a provisional annotation.
Phylogenomics of individual predicted proteins Each predicted C. paradoxa protein was used in a BLASTp query against an in-house database composed of NCBI RefSeq v. 73 proteins with the addition of available algal and protist genome and transcriptome data from dbEST, TBestDB, the JGI Genome Portal (https://genome. jgi. doe. gov (date last accessed 12 April 2019)) and the Microbial Eukaryote Transcriptome Sequencing Project (MMETSP). 25 This database was partitioned into four subsets based on taxonomic provenance: Bacteria, Opisthokonta, remaining nonbacterial or opisthokont taxa, and the MMETSP database. Each subset was searched against independently (BLASTp, E 10 À10 ) using the C. paradoxa proteins and the top 2,000 hits from each search were saved, combined, and sorted by bitscore. The sorted list was parsed such that a taxonomically broad selection of top hits was retained, and the associated proteins were aligned together with the query sequence using MAFFT v7.
29 Read counts were normalized, and any gene that: (i) exhibited a log2 fold change of (þ/À) 1. 5 or greater between the first time point (1ALO) and any other time point, and (ii) had a BLASTp hit to the NCBI nr database, was retained as differentially expressed (DE). A variance stabilizing transformation was applied, and the set of DE genes was then clustered using an agglomerative hierarchical method available via the 'agnes' function. The variance-stabilized data pertaining to cluster members were then plotted and inspected; clusters were manually split, joined and outlying members were removed. To determine whether any clusters exhibited patterns of functional enrichment, the C. paradoxa predicted proteome was annotated using Blast2GO,  30  and member genes of each cluster were used in a Fisher's exact test, as performed in Blast2GO, with the reference set consisting of all 12,652 genes with BLAST hits in the genome.
Gene Ontologies with an uncorrected P-value of <0. 05 were retained. In addition, genes were annotated via the KEGG Automatic Annotation Server (KAAS, https://www. genome. jp/kegg/kaas/ 31 (date last accessed 12 April 2019)) and grouped according to KEGG pathway assignment. Plots were created to illustrate the overall transcriptional response of all members in each pathway; those with a clear up-or down-ward trend comprising the majority of assigned genes were retained for discussion. In all, we identified 4,297 differentially expressed genes in the C. paradoxa light/dark treatment. These genes clustered into 40 predominant expression patterns. The cell cycle genes were identified via BLASTp using curated homologues from other algae, and further qualified using the NCBI 'nr' databases.
Eukaryote tree of life To place C. paradoxa in a broader eukaryote tree of life and test Archaeplastida monophyly, we adapted and expanded the protocol of Price and Bhattacharya  32  to derive de novo ortholog groups (OGs) and construct a 3,000 OG dataset from 115 publicly available eukaryote proteomes. Briefly, EST and/or predicted proteome data were retrieved for each species (see Supplementary Table  S1 ) and OrthoFinder  33  was used to construct ortholog groups (OGs) from the total data. We parsed each group (or putative gene family) and retained those that had low levels of paralogy (>80% of genes in the group were single-copy [i. e. one protein per taxon]) and contained !4 phyla and !10 species. Taxa with multi-copy representative proteins were removed from these groups, and the protein sequences corresponding to each individual group were aligned with MAFFT v.
Genome data and repeat content We sequenced six PacBio RSII SMRT cells of C. paradoxa genomic DNA, producing over 7. 46 Gb of long-read sequence data (see Supplementary Methods). A BLASTx analysis of the PacBio assembly using the NCBI bacterial proteome database identified 36 contigs containing partial bacterial contaminant fragments. These were removed yielding the final assembly of 712 contigs totalling 99. 94 Mb (N50 = 214 kb). Inspection of various k-mer spectra under the expectation of haploidy or diploidy (http://kmergenie. bx. psu. edu (date last accessed 12 April 2019)) using high-quality Illumina reads provided evidence that C. paradoxa is more likely to be a haploid than a highly homogenized diploid genome (Supplementary Fig. S2 ). In support of this hypothesis, a SNP analysis using the PacBio assembly and Illumina short-read data identified 27,675 variants with at least 10x coverage (using 95% sequence identity over 95% of the trimmed read length).
Of these, only 5,016 (or 18%) occurred at a frequency between 30-70%, suggesting that the major class of SNPs, expected at 40-60% for a diploid, was not recovered. Applying an ab initio approach for gene prediction guided by transcriptome data, we predicted 25,831 protein-coding genes in the C. paradoxa genome (excluding bidirectional transcripts, see below). Genes were densely packed, spanning 60. 3% of the genome with a mean intergenic distance of only 770 bp (likely an over-estimation given that we did not predict UTRs), often oriented end-to-end with many short introns (mean = 9. 2 introns/gene; mean length = 86 bp). Such complex gene structures are problematic for HMM-based gene predictors therefore the models presented here will require additional manual curation. BUSCO  35  was used to assess completeness of the predicted proteome and identified 282 of the 303 (93%; 90% complete, 3% fragmented) of the core proteins as being present in the eukaryote (odb9) dataset, suggesting that the assembly was nearly complete.
This represents a major improvement over the previous C. paradoxa predicted proteome  10  that, although found to contain 273 (90%) of core odb9 proteins, was highly fragmented (58% complete, 32% fragmented). To assess the difference in assembly size between the previous (70 Mb) and the current assembly, we aligned the two assemblies using MUMmer 4. 0b2 (https://github. com/mummer4/mummer (date last accessed 12 April 2019)) and find that 65. 2 Mb of the assembly maps one-to-one between the two genomes, with 87,101 duplicate features annotated (type 'DUP') in the new assembly that sum to 34. 7 Mb. The one-to-one and duplicate genome feature lengths sum to 99. 9 Mb, or the length of the new assembly, and thus the previous assembly size was likely an artefact of repetitive, paralogous and/or multi-copy DNA content that was resolved here with the use of longread PacBio sequencing.
Short-read mapping of 105 million Illumina reads to the new assembly indicates that 91. 6% of reads map successfully, with 17. 9 million (18. 5%) having more than one best placement. A BLASTP analysis (e-val =1Â10 À10 ) indicates that 22,678 of 25,831 (87. 8%) predicted proteins from the new assembly have hits to the previous proteome (Supplementary Tables  S2  and S5 ), whereas 27,066 of 32,167 (84. 1%) predicted proteins from the old assembly have hits to the current proteome (Supplementary Table  S3 ). Of the 5,101 proteins from the previous assembly with no hits, 2,355 have TBLASTN hits (e-val =1Â10 À10 ) to the new genome, however only 194 have a BLASTP hit to the NCBI nr database (Supplementary Table  S4 ). We analysed repeat content in the C. paradoxa genome and found that 29. 4% is comprised of repetitive elements and 11.
Interestingly, we find that translation of our assembled de novo transcriptome dataset revealed 3,510 non-redundant (excluding alternate isoforms) transcripts (see Supplementary Table  S6 ) that encode bi-directional and partially or completely overlapping open reading frames (ORFs) of at least 300 amino acids (900 nucleotides) in length. One such example (shown in Fig. 3A ), a ca. 3,050 bp sequence (DN10586_c0_g1_i1: ORFþ) on contig (tig)00001085 contains 13 introns and encodes two bidirectional and overlapping ORFs spanning a gene structure predicted by Augustus. In the forward frame (in relation to the predicted structure), the encoded 718amino acid protein is a putative bacterial-derived ABC transporter with a local BLASTp top hit spanning the entire length of the query to Pontibacter chinhatensis (WP_119433509; 626 AA; E = 0.
0; Supplementary Fig. S4 ). The reverse frame encodes a 715-amino acid protein for which the N-terminal 395 amino acids align via BLASTp to Oscillibacter sp. (CDC69327. 1; 453 AA; E = 2Â10 À22 ) annotated as a 30S ribosomal protein S5. To test whether these ORFs may represent bidirectionally transcribed genes, we mapped stranded RNA-Seq data to these gene structures (e. g. Fig. 3A ), however we found no evidence of their transcription. We consider it extremely unlikely that nucleotide CDS sequences 1-3 kb in size would by chance encode a conserved (i. e. to known NCBI homologues) protein translation (free of stop codons) in the reverse frame after horizontal gene transfer (HGT) to the C. paradoxa nuclear genome and subsequent accrual of 13 spliceosomal introns. Additional work is required to determine the potential biological implication of these findings.
Eukaryote tree of life To place C. paradoxa in a broader tree of life and test for shared ancestry among multiple microbial eukaryote groups, we adapted and expanded the protocol of Price and Bhattacharya  32  to derive de novo ortholog groups (OGs) and constructed a partitioned 3,000 OG dataset from 115 publicly available eukaryote proteomes (Supplementary Table  S1 ). The consensus maximum-likelihood tree (Fig. 4  and Supplementary Fig. S10 ) is consistent with the monophyly of most major eukaryote phyla as has been previously published (see below). This tree also provides strong support for, and therefore confirms a single origin of the Archaeplastida, whose common ancestor hosted the cyanobacterial primary endosymbiosis that gave rise to the plastid in eukaryotes. 10, 49, 50 This result is often found when using multigene datasets from the nuclear  51, 52  and mitochondrial compartments,  53  but Archaeplastida non-monophyly has also been reported in several cases  52    Phylogeny showing the position of Cyanophora paradoxa and other glaucophytes in the eukaryotic tree of life.
This tree was constructed using a partitioned 3,000 OG dataset from 115 publicly available eukaryote proteomes, as described in the text and reference. 32 All nodes have 100% bootstrap support unless shown otherwise. The full tree is presented in Supplementary Fig. S10. In support of the monophyly hypothesis, analysis of single genes from the C. paradoxa genome by Price et al. 10  showed that of 4,445 maximum-likelihood trees analysed, over 60% supported a sister group relationship between glaucophytes and red and/or green algae plus plants at a bootstrap support !90%. In addition to the monophyly of the glaucophyte and green lineages based on plastid-encoded genes, Lee et al. 55  also identified 23 OGs in the nuclear genomes of both lineages that were transferred to the nucleus (i. e. totalling 93 gene families) from the genome of the ancestor of the Glaucophyta þ Viridiplantae plastid.
This shared history of endosymbiotic gene transfer (EGT) supports the monophyly of these two lineages within Archaeplastida. In comparison, only four such OGs are common to all three lineages, and only one primordial OG is common to the greens and rhodophytes. Our genome-wide analysis also strongly supports the early divergence of the red algae, with glaucophytes and Viridiplantae forming a well-supported clade (100% bootstrap support), a conclusion that was also reached in a recent study of nuclear data [351 protein dataset, maximum-likelihood and Bayesian analysis; see Fig. 1  in Brown et al. 52  ] and of plastid data [60 proteins shared by the Archaeplastida and cyanobacteria; see Fig. 5 , Supplementary S23 in Lee et al. 55  ). This conclusion is at odds with several other studies. For example, Li et al.
56  identified compositional biases among first and third positions of nucleotides in plastid amino acid codons and settled on an early divergence of glaucophytes based on protein data and plastid morphology (i. e. presence/absence of PG). They could not, however, significantly reject competing topologies. A basal divergence of glaucophytes within Archaeplastida was also found by Ponce-Toledo et al. 57  in an analysis of a concatenated dataset of 97 plastid proteins that included the putative bacterial ancestor of plastids; i. e. the lineage including the freshwater species Gloeomargarita lithophora. This topology suggested that plastid primary endosymbiosis occurred in a freshwater environment, and glaucophytes are freshwater taxa. 9 However, our finding of an early split of Rhodophyta within Archaeplastida does not argue against a freshwater environment for plastid endosymbiosis, because many early diverging red algal clades include freshwater taxa such as in the Compsopogonophyceae and Porphyridiophyceae.
Genes of tryptophan,  88, 89  isoprenoid, and menaquinone core synthesis (Cenci et al. , unpublished data) were also possibly transferred to support the required biochemical fluxes in the cyanobiont. In contrast, the overflow of carbon from the cyanobiont was putatively exported to the host cytosol where chlamydial enzyme effectors would have connected the tripartite symbiosis by incorporating excess carbon into host glycogen stores. 89, 90 o reassess the chlamydial contribution using the improved genome assembly from C. paradoxa in combination with an expanded bacterial genome database, we manually inspected the phylogenomic trees and found 35 well supported and 2 more weakly supported candidates (Supplementary Table  S8 ). The well-supported chlamydial set includes 17 HGTs shared by all Archaeplastida lineages, whereas 3 and 5 genes are putatively shared exclusively with green and red algae, respectively.
Conclusive remarks In summary, the significantly improved genome assembly presented and analysed here provides several important insights. First, the phylogenetic analysis of a partitioned 3,000 OG dataset from 115 eukaryote proteomes that includes the new C. paradoxa gene models provides robust support for Archaeplastida monophyly. This analysis also supports with high bootstrap values most of the other existing supergroups. Noteworthy aspects of the C. paradoxa genome include its gene richness and low repeat composition with a relatively small contribution made by LTRs and LINEs. The finding of shared overlapping UTRs may indicate selection in at least one instance to co-localize functionally related genes. Any putative functional role of accessory ORFs encoded within the transcripts of C.
Funding This research was funded by the  National Science Foundation  ( 0936884  and  1317114 ) to D. B. A. P. M. W. appreciates support from the  Deutsche Forschungsgemeinschaft  (grants  EXC 1028  and  WE 2231/8-2 ). S. B. and U. C. acknowledge funding by the  ANR  [grant  ANR-18-CE13-0027  (MATHTEST)] and the  Region Hauts de France  ( Alibiotech grant ).
Background-purpose Totally extraperitoneal (TEP) endoscopic hernioplasty and Lichtenstein hernioplasty are the most commonly used approaches for inguinal hernia repair. However, current evidence on which is the preferred approach is inconclusive. This updated meta-analysis was conducted to track the accumulation of evidence over time. Methods Studies were identified by a systematic literature search of the EMBASE, PubMed, Cochrane Library, and Google Scholar databases. Fixed-and random-effects models were used to cumulatively assess the accumulation of evidence over time.
Introduction Inguinal hernia repair is the most common operation in general surgery with more than 20 million performed annually worldwide  [1]. Most patients with an inguinal hernia are symptomatic and the treatment of choice is surgical repair with mesh using open or laparo-endoscopic approach. The use of mesh varies worldwide from 0 to 5% in low-resource countries to 95% in high-resource countries. The Swedish National registry reported that for the year 2015, the percentages of inguinal hernia repair techniques were as follows: Lichtenstein hernioplasty 64%, totally extraperitoneal (TEP) hernioplasty 25%, transabdominal preperitoneal (TAPP) hernioplasty 3%, open preperitoneal hernioplasty 3. 3%, and tissue repair 0. 8%. The German Herniamed registry reported the following data for the period from 2009 to 2016: TAPP hernioplasty 39%, TEP hernioplasty 25%, and Lichtenstein hernioplasty 24%.
There is a lack of data from America and Asia  [1]. Some possible complications of hernioplasty include recurrence necessitating reoperations in 10-15% of cases and chronic pain (lasting more than 3 months) in 10-12% of cases, which may lead to long-term disability  [1]. To date, the evidence comparing TEP hernioplasty to Lichtenstein hernioplasty is non-conclusive  [2, 3]. However, there has been new published evidence since the most recent meta-analysis. Therefore, we decided to perform an updated traditional and cumulative meta-analysis to estimate the impact of the new studies on the robustness of the statistical significance of existing meta-analyses comparing TEP hernioplasty and Lichtenstein hernioplasty. Recurrence rate and chronic persistent pain were selected as primary outcomes.
Literature search With the use of the search terms in the free text and Medical Subject Headings terms ("laparoscopic or endoscopic total extraperitoneal inguinal repair", "laparoscopic or endoscopic total extraperitoneal inguinal hernioplasty", "open with mesh Lichtenstein inguinal hernia repair", "Lichtenstein's technique", "inguinal hernia repair with mesh", "TEP", "inguinal hernia", or "randomised or randomized controlled trial"), a systematic search of literature published over the last 30 years was performed using the EMBASE, Medline (PubMed), Cochrane Library, and Google Scholar databases. A grey literature search was also performed in the clinicaltrials. gov website. References of the retrieved articles were checked manually for additional studies. Disagreements between the authors were resolved by consensusbased discussions.
Data extraction and outcomes Two reviewers (PG and NA) independently extracted the following summary data from the included studies: name of authors; year of publication; number of patients included in the TEP and Lichtenstein hernioplasty cohorts; duration of operation; conversion rate; rates of haematoma and seroma formation; incidences of wound infection, vascular injury, and visceral injury; time to return to usual activities; incidence of persisting pain or persisting numbness; and recurrence rate.