dataesr/scientific-paragraphs-categorization huggingface dataset:
Chromosome-level genome assembly The genome of M. mercenaria was sequenced and assembled using a combination of sequencing technologies, resulting in an assembly size of 1. 86 Gb with a N50 size of 83 Mb and a GC content of 35%. We reconstructed 19 chromosomes with the help of Hi-C data (Fig. 1 ) and no contamination was detected in the final DNA sequences (Fig. S1 ). The completeness of the genome assembly scored 76. 4% using the Mollusca database from BUSCO and 91. 8% using the Metazoan database, ranking our assembly among the best ever obtained for Venerida (Table  S1 ). Comparison of our assembly to another assembly published recently (M. mercenaria YKG,  [24] ) revealed inversions and translocations (Fig. 2 ). Most of the chromosomes showed minimal differences (Fig. 2 , top panels) whereas chromosomes 10, 14 and 16 displayed large structural differences as well as possible duplication events (Fig.
Tumor necrosis factor and C1q Genes belonging to TNF and C1q were manually curated in order to better analyze domain content and evolution because of the role of these genes in immunity and cancer regulation. TNF genes were considered if they had a TNF domain (IPR006052) or were within an orthogroup having genes containing a TNF domain (Table  S8 ), resulting in a total of 76 genes in M. mercenaria. As described above, these genes were mostly duplicated in tandem on the genome although some were also found in segmental duplication (Table  S8 ). Ortholog analysis clustered TNF members in 13 distinct OGs (Table  S8 ). One OG (OG0000926) had all species represented where M. mercenaria was not the species having most represented copies (Table  S9 ). Four OGs had representative members from the Bivalvia with the exception of the Pectinida family, including 2 OGs (OG0000639 and OG0000960) showing markedly higher numbers of representatives in M.
The number of TM domains was not related to the orthogroup clustering. Subsequently, TNF domains were extracted to perform a phylogenetic analysis (Fig. 4 ) that allowed the clustering of the domains into 6 families supported by bootstrap values higher than 70%. Most of these genes were clustered similarly to the OGs excluding OG0000926, which segregated into one branch having only members belonging to M. mercenaria set apart from two other branches. The orthogroups OG00005640, OG0034212, OG0043344 and OG0043346 formed a monophyletic group with a bootstrap of 100%, with the first OG specific to Venerida and last three specific to M. mercenaria (Fig. 4 ). Similarly to TNF genes, C1qDC genes were considered and manually curated (total of 408 genes in M. mercenaria, Fig. S5 ) if they contained at least one C1q domain (IPR001073) or a tumor necrosis factorlike domain superfamily (IPR008983).
philippinarum in which deleted Steamer elements were recovered during RepeatMasker searches on the nine genomes devoid of complete Steamer elements. Finally, no Steamer element could be detected in one third of the bivalves analyzed. We also looked for potential Steamer elements more broadly and systematically by searching the NCBI nucleotide database with the same conserved RT/RnaseH domain from the Steamer element of M. arenaria. Fifteen sequences were so selected from organisms belonging to different phyla. The Steamer family was well supported (bootstrap 90%) and included 23 elements derived from bivalves. These elements were named with the prefix "Ste" for "Steamer", followed by a code referring to the name of the species and a number in case of more than 1 sub-family. The analysis of the genomes revealed only one Steamer subfamily per species except for Mytilus coruscus and Anadara broughtonii with 2 and 3 sub-families, respectively, even though BLAST searches on public databases also revealed a second sub-family in M.
Although they are phylogenetically close, the fish elements do appear to form an independent group (bootstrap of 32 not shown in Fig. 6 ); the element of Branchiostoma belcheri common to both phylogenies (XM_019773121) is part of the C10 branch, and that of Strongylocentrotus purpuratus (XM_011662828) is part of a different branch. This data indicates that the sequences referred to as SLEs seem to correspond more to the whole or part of the Gypsy retrotransposons of the C-clade. In addition,  Metzger et al. (2018)   [31]  point out that many of their SLE sequences have been annotated as K02A2. 6-like, based on a more distantly related Caenorhabditis elegans retrotransposon. As we note the same in our NCBI searches, it appears that such annotation and element may also be related to the C-clade.
But the SLEs 'Crassostrea virginica' , 'Mercenaria mercenaria 2' (which corresponds to our SteMemer) and 'Cerasoderma edule 1' do belong to the Steamer family. This seems to confirm that in addition to the 19 species we obtained, the Steamer family is also represented in Ishadium recurvum, Siliqua patula, Limecola balthica and Panepoa generosa. The distribution of the Steamer family within species is quite peculiar. Although almost exclusively restricted to bivalves, it could not be detected in 6 of the genomes studied. Of course, the absence of detection does not mean absence of element even if we tried to be as exhaustive as possible. Indeed, in addition to the simple LTRHavest search, we used both a Repeat-Masker approach and a BLAST search on public databases (using the identified Steamer sequences) in order to either detect a possible Steamer element in apparently devoid species (which allowed us to identify the deleted copies in R.
Based on the universal single-copy orthologs (BUSCO) analysis using the Mollusca_odb10 and Metazoa_odb10 lineages, we assessed the quality of the final assembly and contrasted it to other bivalve genome assemblies. Blobtools  [85]  was run with default parameters on the final assembly of the clam in order to detect potential contamination. For that, reads from Illumina were mapped on the assembly using BWA mem algorithm  [86]  and BLASTn version 2. 11. 0  [87]  was also computed on the NT database from NCBI  [88]  and given as input to blobtools. In order to compare our assembly and M. mercenaria YKG genome assembly, nucmer from MUMmer  [89]  was run with default parameters comparing each chromosome from one strain to all chromosomes from the second strain. Mummerplot was used to generate dot plots of the results.
LTR-retrotransposons and steamer elements identification We investigated LTR-retrotranspons using a detailed and precise pipeline customized for M. mercenaria. This was done because we were interested in the characterization of Steamer elements (part of the C-clade of the Gypsy superfamily) in Bivalvia, given the suspected role of these elements in carcinogenesis and the increasing reports of leukemia in the hard clam. Thus, we first choose to refine the detection of LTR-retrotransposons by running LTRHarvest  [90]  on all Bivalvia genomes using the following parameters "-minlenltr 80 -maxlenltr 1200 -mindistltr 2500 -maxdistltr 11000 -similar 80. 0". The outputs were combined and filtered using BLASTx  [87]  (evalue less than 10 -15 ) against an in-house database (267 RT/RNaseH or pol sequences representing the different known clades of LTR-retrotransposons, plus DIRS and Polinton sequences used as competitors) assigning, when possible, the resulting sequences to each LTR-superfamily (Gypsy, Copia or BEL/Pao) if more than 8 of the first ten matches were assigned to the same superfamily; uncertain assignation were manually curated.
Sequences belonging to each superfamily were clustered into families using uclust from USEARCH version 11. 0. 667 [91]  with parameter "-cluster_fast -id 0. 8 -sort length -strand both". A multiple alignment was done on each cluster of sequences and on the remaining single sequences (clustered together by species). Then sequences were insertscleaned using an in-house program trimming the nucleotides not conserved in at least 80% of the aligned sequences. This pipeline (from uclust to trimming) was performed twice to get a better clustering. To identify Steamer elements, we first extracted and translated the RT/RNaseH domain from the Gypsy sequences obtained with LTRHarvest  [90]  for all 20 species. This was done using BLASTx  [87]  (E-value less than 10E-5) against an in-house database of RT/RNaseH of 215 Gypsy elements representing a large part of the Gypsy clades  [32] ; best matches positions guided the extraction with boundaries of RT/RNaseH domains being determined according to those defined for RT 5′ part and RNaseH 3′ part of Gypsy multiple alignments defined in the Gypsy Database  [92].
This Gypsy dataset (including Steamer elements from M. arenaria and E. directus, AIE48224. 1 and MH025794, respectively,  [31] ) was used as database to retrieve potential Gypsy elements from the C-clade using BLASTp  [87]  and keeping sequences having the best match with C-clade reference elements with an E-value less than 10E-50 and at least 300aa covered. Here, we kept the single sequences and a consensus sequence per previously defined-cluster. To identify Steamer elements more widely in metazoans, we performed tBLASTn  [87]  analyses with the RT/RNaseH domain of the Steamer element from M. arenaria as query (E-values 1E-140, query cover > 95%, no filter) on genomic and transcriptomic databases (nr/nt, wgs, est. , TSA) available at NCBI (https:// www. ncbi. nlm. nih. gov/). We also used phylogenetic approaches to determine the position of the C-clade elements in each branch.
Phylogenetic analyses were performed as in Thomas-Bulle et al. [32]  on amino acid sequences corresponding to the RT/ RNaseH domains of the newly characterized sequences and reference elements from the C-clade. Multiple alignments of these protein sequences were performed using MAFFT  [93]. After a manual curation of the alignments, phylogenetic analyses were conducted using Neighbor Joining and the pairwise deletion option of the MEGA5. 2 software  [94]. Using Topali2. 3  [95] , the best-fitted substitution model retained was the JTT model with a gamma distribution. Support for individual groups was evaluated with non-parametric bootstrapping using 100 replicates. Finally, we used a RepeatMasker version 4. 1. 0 [96] approach with the addition of "Concatenate_sequences. py" concatenating hits closer than 500 bp and removing hits smaller than 300 bp length  [32]  to (i) search Steamer elements in bivalve genome devoid of a complete copy, and (ii) retrieve all possible Steamer copies in each genome.
Genome annotation A previously published transcriptome  [9]  of M. mercenaria, predicted genes from Song et al. [24] , proteins belonging to Mollusca and reviewed sequences belonging to Bilateria species from UniProt database  [99]  were mapped on the repeat-masked genome with BLAT  [100]  to rapidly identify the position of the sequences on the genome. To refine the alignments, only matches with more than 80% identity were kept and given to exonerate version 2. 4. 0 using est2genome model and protein2genome model for transcriptome and proteins mapping, respectively. Transcriptome alignments were filtered with at least 98% of identity and at least 90% of the transcript length matching the genome while proteins hits were filtered with at least 50% of identity and at least 50% of the protein length matching the genome.
An ab-initio prediction was done using SNAP  [101]  with training on the transcriptome sequences mappings. Finally, Gmove  [102]  combined all different resources listed above with the addition of the previous gene prediction to build the gene set. Finally, this gene set was given to Gmove  [102]  with the addition of the mapped predicted annotation from Song et al. [24]. Functional annotation was done on each resulting protein by alignments to the nr database  [103]  using BLASTp version 2. 11. 0  [87]  by keeping the best three matches. Domains were defined using InterProScan 5. 36-75. 0 [104]  with the default parameters. Finally, correspondence was done between InterProScan identifications and gene ontology terms  [105, 106]. The assessment of the predicted proteins was done based on BUSCO by mapping the Metazoa_obd10 database  [107]  on all considered assemblies.
The script "agat_sp_statistics. pl" from Another Gtf/ Gff Analysis Toolkit (AGAT) was run against all genomes and related GFF files to compute all annotation metrics. In order to compare annotations between M. mercenaria and M. mercenaria YKG gene prediction, Orthofinder version 2. 4. 1  [28]  was ran using the two proteomes with default parameters. In addition, Best Reciprocal Hits (BRH) were determined to retrieve 2 by 2 orthologs using BLASTp matches filtered on an E-value of 10E-5. Moreover, GO terms were assigned to each gene from each assembly using IPR2GO database and TopGO library from R was used to generate statistics of GO enrichment in genes present in one strain but not found in the other one and conversely.
Gene duplications and gene family analysis on 20 Mollusca species Duplication events were assessed by running MCScanX  [108]  with default parameters and as input the BLASTp file result of all proteins predicted against each other and the M. mercenaria genome sequences. We also ran 'duplicate_gene_classifier' , in order to reveal all different type of duplications detected in our genome assembly. GO terms were assigned to each genes using IPR2GO database. Then, TopGO R library was used to generate statistics of GO enrichment in different categories of genes (e. g. , tandem duplicated genes). Predicted M. mercenaria proteome was compared to the newly published hard clam genome YKG (GCA_014805675. 1, [24] ) as well as to other published genomes of Bivalvia representing 6 orders including Venerida with R.
philippinarum (GCA_014805675. 1, [37] ), C. sinensis (GCA_012932295. 1, [35] ), L. rhynchaena (GCA_008271625. 1, [36] ) and A. marissinica (GCA_014843695. 1, [34] ), Myida with Dreissena rostriformis (GCA_007657795. 1, [109] ), Adapedonta with Sinonovacula constricta (GCA_007657795. 1, [110] ), Arcida with A. broughtonii (no accession number,  [111] ), Ostreida with C. gigas (GCA_902806645. 1, [112] ), C. virginica (GCA_002022765. 4, [113] ), O. edulis (unpublished), S. glomerata (GCA_003671525. 1, [114] ), Pectinida with Mizuhopecten yessoensis (GCA_002113885. 2, [115] ) and P. maximus (GCA_902652985. 1, [116] ) and Mytilida with M. philippinarum (GCA_002080025. 1, [117] ), Limnoperna fortunei (GCA_003130415. 1, [118] ), M. coruscus (GCA_011752425. 2, [119] ) and M. galloprovincialis (GCA_900618805.
1, [44] ) with the addition of an outgroup species from the Gastrodopa class, Aplysia californica (GCA_000002075. 2, [120] ). These Predicted proteomes were downloaded from public databases or requested from authors if not public. A. californica was used as outgroup. In order to define gene families, Orthofinder  [28]  was used on all previous proteomes with default parameters (P. fucata was removed from the analysis as it had less than 80% of the proteome within orthogroups). From Orthofinder results, we used the single copy gene OGs and concatenated the proteins per species to generate the species tree using MAFFT online  [93]  with default parameters adding the bootstrap calculation and using iTOL to generate a graphical representation of the tree. TNF and C1q domain-containing genes belonging to M.
mercenaria were manually identified and curated. Briefly, the identification was first based on the presence of the domain of interest, with the second step being the retrieval of all genes being in the same OG. Then, genes not having a start or end codon or having a deletion region were verified and corrected where possible, using IGV  [121]  with RNAseq data for validation using splicing sites and mapped proteic and transcriptomic data that served for the annotation process. Once validated, all domains of interest were extracted from all considered species using an in-house script. Multiple alignments of all retrieved domains (444 and 2217 sequences of TNF and C1q domain, respectively) were done with the MAFFT server using MaxAlign tool (293 and 408 curated sequences left for TNF and C1q domains respectively) to improve the alignment and run a phylogeny with bootstrap of 1000 on a Neighbor Joining method.
Thousands of unique noncoding RNAs (ncRNAs) are expressed in human cells, some are tissue or cell type specific whereas others are considered as house-keeping molecules. Studies over the last decade have modified our perception of ncRNAs from transcriptional noise to functional regulatory transcripts that influence a variety of molecular processes such as chromatin remodeling, transcription, post-transcriptional modifications, or signal transduction. Consequently, aberrant expression of many ncRNAs plays a causative role in the initiation and progression of various diseases. Since the identification of its developmental role, the long ncRNA DNM3OS (Dynamin 3 Opposite Strand) has attracted attention of researchers in distinct fields including oncology, fibroproliferative diseases, or bone disorders.
FUNDING INFORMATION This work was supported by funds from  Institut National de la Santé et de la Recherche Médicale (Inserm) ,  Centre National de la Recherche Scientifique (CNRS) , the  Association Française contre les Myopathies ,  AFM  (through grant HuMusmiR # 17708 ), the  French Government (Agence Nationale de Recherche, ANR) ANR-PRCI FIBROMIR , and  ITMO Cancer Aviesan (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Science and Health)  within the framework of the  Cancer Plan  (Plan Cancer 2018 ARN non-codants en cancérologie: du fondamental au translationnel n 18CN045).
The Phase 3 ICARIA-MM (NCT02990338) and IKEMA (NCT03275285) studies demonstrated that isatuximab (Isa) plus pomalidomide (P) and dexamethasone (d; Isa-Pd) or carfilzomib (K) and d (Isa-Kd) improved progression-free survival (PFS) versus Pd or Kd in patients with relapsed and/or refractory multiple myeloma. In this post hoc analysis of patients with soft-tissue plasmacytomas, we evaluated Isa-Pd/Isa-Kd efficacy using central radiology and central laboratory assessments. Given the low incidence of soft-tissue plasmacytomas (7. 8 %, ICARIA-MM; 6. 3 %, IKEMA), efficacy data were pooled across the two studies. PFS (HR, 0. 47; 95 % CI, 0. 21-1. 08), overall response rate (50. 0 % vs 17. 7 %), and very good partial response or better rate (26. 9 % vs 11. 8 %) were improved with Isa-Pd/Isa-Kd versus Pd/Kd, with consistent improvements within individual studies.
Isa acts through multiple mechanisms to kill myeloma cells  [14, 15]. In the Phase 3 ICARIA-MM study (NCT02990338), Isa in combination with pomalidomide and dexamethasone (Isa-Pd) significantly improved progression-free survival (PFS) compared with Pd alone (median PFS 11. 5 vs 6. 5 months) in patients with relapsed and refractory MM (RRMM; hazard ratio [HR], 0. 60; 95 % confidence interval [CI], 0. 44-0. 81; p =. 001) [16]. Based on these results, Isa-Pd is approved for adult patients with RRMM who have received ≥ 2 prior therapies, including lenalidomide and a protease inhibitor. The Phase 3 IKEMA study (NCT03275285) demonstrated that Isa in combination with carfilzomib and dexamethasone (Isa-Kd) significantly improved PFS compared with Kd alone in patients with relapsed MM (HR, 0. 53; 99 % CI, 0.
Daratumumab, another anti-CD38 monoclonal antibody, appeared to have lower efficacy as a single agent or in combination with lenalidomide and dexamethasone in MM patients with soft-tissue plasmacytomas than was observed in those without  [21]. Similarly, Pd had limited efficacy in patients with MM and soft-tissue plasmacytomas  [22]. We performed a post hoc analysis of the efficacy and safety of Isa-Pd/Isa-Kd versus Pd/Kd in patients with relapsed and/or refractory MM and pre-existing soft-tissue plasmacytomas from ICARIA-MM and IKEMA. Due to the low incidence of pre-existing soft-tissue plasmacytomas within each study, efficacy data was pooled across the 2 studies to achieve sufficient sample size. Safety data are reported individually per study.
Outcomes In this pooled post hoc analysis, we evaluated the efficacy of Isa-Pd/ Isa-Kd versus Pd/Kd in patients with RRMM and pre-existing soft-tissue plasmacytomas. The primary objective was to assess the impact of Isa-Pd/Isa-Kd versus Pd/Kd on PFS (as per IRC). Secondary endpoints included ORR, ≥VGPR, and CR rates. OS was determined for ICARIA-MM only as it was not mature at data cutoff for IKEMA. MRD was assessed in patients achieving CR in ICARIA-MM and in patients achieving ≥VGPR in IKEMA. Because MRD was not assessed in the same subset of patients in the two studies, pooled MRD analysis was not conducted. The safety analyses were not pooled as isatuximab was combined with drugs that had different safety profiles in the two studies. Safety results according to the treatment arm from each individual study were summarized for the subgroups of patients with relapsed and/or refractory MM and soft-tissue plasmacytomas.
Acknowledgments The  ICARIA-MM  and the IKEMA studies were sponsored by  Sanofi. The authors thank the participating patients and their families, and the study centers and investigators, for their contributions to the studies. We are grateful to  Marie-Laure Risse  for her support and contributions, and  Diane Stash  for her assistance with the radiology images. Medical writing support was provided by  Smitha Reddy, PhD  of Elevate Scientific Solutions, contracted by  Sanofi  for publication support services.
Data processing X-ray-based deviation data in 6 DOF (lateral, longitudinal and vertical translational position deviations in millimeters; roll-, pitch-and yaw-angles for rotational deviations in degrees) were retrieved from PDF-file records which are generated for every treatment session of a patient. A deviation/magnitude vector was calculated. (d = ̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅ ̅ x 2 + y 2 + z 2 √ = ̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅ lateral 2 + longitudinal 2 + vertical 2 √ ) to show the absolute translational deviation. For patients receiving SRS or FSRT, coplanar (treatment couch 0 • ) and non-coplanar (treatment couch other than 0 • ) beam configurations are often used to obtain highly conformal, sharp dose gradients outside the PTV to minimize dose to adjacent tissue or organs at risk  [20, 21].
Lewis and collaborators were investigating whether the ExacTrac monitoring frequency of intrafraction patient motion in stereotactic radiosurgery can be reduced. A pre-treatment image was acquired and further images at two time points during the treatment (about 8 and 13 min after first image). They analyzed data sets of 104 patients and did not find a correlation between patient motion over time, in direction or magnitude, and duration of treatment. They came to the conclusion that the imaging frequency could be reduced even further  [25]. An important aspect of the present study is the automated gating function of the ExacTrac Dynamic system. If the deviation in 6 DOF exceeds a prescribed tolerance range, the irradiation is stopped automatically without the need of any manual intervention.
Smit Zaveri The Power of Open Initiative with a similar mission. Every book is available in multiple formats and can be read online, offline or downloaded and printed. Translation and versioning tools help customize the books for localized require ments and these resources become available to other users as well, creating a multiplier effect and amplifying impact. 4 In just seven years, StoryWeaver has grown 50 times in size and scope, from a repository of 800 books in 24 languages to over 45 000 books in 314 languages. These books have been read over 18 million times on the platform by users in 150 countries. Pillar 2: ACCESS When I began working as a children's book editor, I firmly believed that I understood what it meant to be in publishing and how the industry functioned. I knew what a good editor did -she advocated for her books and her authors and illustrators everywhere, with her publisher, her sales team, and with the world at large.