dataesr/scientific-paragraphs-categorization huggingface dataset:
The collaborative work between ESTS and ITMIG has recently produced a landmark result, that is the harmonization of both prospective databases as regards to the minimum dataset, which are now identical in terminology, wording and type of data fields. This will certainly facilitate any future common project between the two Organizations. The International Association for the Study of Lung Cancer (IASLC) launched in 2010 the Staging Project for the release of the 8 th edition of the TNM classification of the thoracic tumors. For the first time in history, the IASLC Staging and Prognostic Factors Committee (SPFC) decided to create a thymic staging domain with the aim of proposing a TNM staging system for the thymic tumors. The thymic domain asked the major thymic interest groups worldwide to collaborate in the data collection.
The ESTS promptly replied and contributed with the data from its retrospective thymic database. The results of this extraordinary collaborative effort involving ITMIG, ESTS and JART was the creation of an impressive retrospective thymic database with more than 8,000 cases which allowed to formulate the 8 th edition of the IASLC/UICC/AJCC TNM classification of thymic tumors  (8). After the completion of the 8 th edition of the TNM, the IASLC SPFC is now working at the next phase of the Staging Project which will eventually lead to the release of the 9th edition of the TNM expected in 2024. ESTS will certainly provide the necessary support to the project with its prospective thymic registry which contains more than 1,100 patients as of November 2017.
Conclusions The ESTS thymic database represents a fundamental storage of information about patients with thymic tumors. It is free, easily accessible to any ESTS institution, web-based, periodically maintained and updated. Any participating Institution can have access to its own data and it can also be used as internal database for any study using your own data. Any participating Institution can propose a study using the data of the whole database and, upon acceptance from the ESTS Database Committee, it can receive the data for the analysis. We believe that the ESTS thymic database represents an invaluable source of data to be used by the ESTS community for important studies in the advancement of the management of thymic tumors.
The genomes of phages E215 (66,789 bp) and E217 (66,291 bp) also had a high level of similarity (97% identity over 98% of their length), are related to the genomes of members of the P1virus subfamily of the Myoviridae, and closely resemble the genome of Pseudomonas phage vB_PaeM_CEB_DP1. In order to discard temperate phages and, more broadly, phages that could serve as vehicles for undesirable functions, we searched for similarities between all putative viral open reading frames (ORFs) and a custom database of genes expressing bacterial virulence factors, antibiotic resistance, and integrases/excisionases/recombinases. We found that the genomes of phages PYO2, DEV, E215, and E217 do not encode proteins with similarity to undesirable functions, leading us to classify them as virulent. On the contrary, as reported in Table  S4 , the genomes of phages E220 and S218 contained open reading frames with high levels of similarity to genes annotated as integrases in the ACLAME database  (19).
Genomic DNA extracted from purified high-titer phage preparations was subjected to standard Illumina library preparation protocols and sequenced on an Illumina Mi-Seq instrument at the CNR IBBIOM Institute in Bari, Italy, to generate paired-end (2 ϫ 250 nucleotides) sequence reads. Raw paired-end sequence data were subjected to stringent quality trimming and removal of library adapters using Trimmomatic software  (43)  and assembled using the SPAdes (v3. 7. 1) program  (44)  and k-mer lengths of 75, 97, and 119. Each genome was assembled as a single contig and deposited in GenBank. BLAST similarity searches of the complete genome sequences against the sequences in GenBank recovered high levels of identity and contiguity with previously sequenced genomes and allowed taxonomic assignment of each isolate (Table  S4 ).
An in-house database of undesirable genes was constructed by merging entries from the ACLAME database of mobile elements  (19)  whose descriptions contained any of the terms "integrase," "excisionase," "recombinase," or "repressor" with those from the Comprehensive Antibiotic Resistance Database (CARD)  (45)  and the Virulence Factor Database (VFDB)  (46). All ORFs with the ATG, GTG, or TTG start codon were inferred from viral genome sequences using a custom Python script and used as queries for BLASTX  (47)  searches (E value cutoff, 5eϪ04) against the undesirable gene database. Transduction assay. Phages were tested for their ability to transduce the tetracycline resistance (Tc r ) marker from PAO1Tc r into wild-type PAO1. An aliquot (100 l) of a high-titer lysate (Ͼ1 ϫ 10 10 PFU/ml) obtained in PAO1Tc R was used to infect a 10-ml overnight culture of the recipient strain PAO1.
To these, phages PAK_P1 and PAK_P4, previously characterized for their therapeutic efficacies in mouse infections  (13, 21) , were added; both are Myoviridae, have a head diameter of 80 nm and a tail of about 130 nm, and share no homologies with the other 4 phages in the cocktail. Their genome sequences (GenBank accession number NC_015294 and KC862300, respectively) are 93,198 bp and 93,147 bp, respectively, with 93% identity. Our final cocktail included these 6 phages: PYO2, DEV, E215, E217, PAK_P1, and PAK_P4. The cocktail was composed of phages mixed at the same number of PFU per milliliter, and the cocktail was prepared immediately before each experiment to ensure accurate phage titers. Biofilm disruption. Two methods were used to monitor biofilm disruption: fluorescence microscopy and crystal violet staining.
At 1 h after injection of the bacteria into the larvae, a fixed dose of phage cocktail (4,500 PFU/larva) was injected. Statistical analysis. Statistical analysis was performed using Student's t test or two-way analysis of variance (ANOVA) with the Tukey test or the chi-square test with the Yates correction. P values for Kaplan-Meier curves were calculated by the Mantel-Cox test. Statistical analysis was done using Graph-Pad software (http://www. graphpad. com/quickcalcs/). Accession number(s). The GenBank accession numbers for the phages are MF490236 for vB_PaeP_ PYO2, MF490238 for vB_PaeP_DEV, MF490241 for vB_PaeM_E215, MF490240 for vB_PaeM_E217, MF490237 for vB_PaeP_E220, and MF490239 for vB_PaeS_S218.
ACKNOWLEDGMENTS We thank  A. Bragonzi  from the  Infection and Cystic Fibrosis Unit at San Raffaele  for providing clinical strains and  Z. Alavidze ,  M. Kutateladze ,  N. Chanishvili , and  T. Chikvashvili  from  The Phage Therapy Center of Georgia  for providing the Phagyo and  Intesti Bacteriophage  preparations. We also thank  S. Binda  and  L. Pellegrinelli  for helping us with the isolation of phages, as well as  N. Santo  for electron microscopy of our phages. The plasmid expressing GFP was a generous gift from  C. Penaranda  and  D. Hung ,  Massachusetts General Hospital. Strain PAO1 pilA was generously provided by  F. Imperi ,  Department of Biology and Biotechnology, Sapienza University, Rome, Italy. We thank  M. A. Nicola  ( Imagopole, Institut Pasteur ) for her assistance. We are grateful to  M.
Relationships to worldwide human P. vivax isolates To analyze the relationship between our 11 P. vivax-like isolates and human P. vivax, we completed our dataset with 19 published human P. vivax genomes (S1 Table)  [38]. All sequencing reads were aligned against the PvP01 reference genome  [15] , and SNVs were called and filtered as described in the Materials and methods section. Maximum likelihood phylogenetic trees were then produced based on 100,616 SNVs. Our results clearly demonstrate the presence of 2 significantly distinct genetic clades (with a bootstrap value of 100) composed of P. vivax-like strains on one side and human P. vivax isolates on the other side (Fig  3 ). This result differs from previous results suggesting that human strains formed a monophyletic clade within the radiation of ape P.
Because of its high DNA content, the Pvl06 isolate was sequenced using PacBio chemistry. After a greater than 8-kb-size selection of DNA fragments using the BluePippin Size-Selection System (Sage Science), the library for this Pvl06 sample was sequenced using P6 polymerase and PacBio chemistry version C3/P5 in 20 SMRT cells. Raw sequence data are deposited in the European Nucleotide Archive. The accession numbers can be found in S1 Table. inferences (see S1 Table ). BWA  [49]  was found to be as specific as reads from Laverania samples did not map onto the reference P. vivax genome PvP01 (Otto, pers. com. , results not shown). The 11 newly generated P. vivax-like samples, together with the already published 19 P. vivax samples and the reference strain P. cynomolgi  [8]  reads, were therefore mapped against the PvP01 reference genome using BWA version 0.
1. 19 [49]  (parameters-q 20 -Q 20 -C 50) followed by bcftools to remove indels (call -c -V indels)  [49]. SNVs were filtered using VCFTools  [59]  to keep variants that have been successfully genotyped in 100% of individuals, with a minimum depth of 5 reads per position. Allelic frequencies were also estimated for each variant at each SNV in order to select the dominant allele in multiple infections (-minDP 5max-missing 1-freq). Then, the files in VCF format were transformed into tab-delimited text format, using the "vcf-to-tab" Perl module, and finally transformed into fasta format using a homemade Perl script that could be obtained directly by contacting corresponding authors.
Gene family search For the P. vivax-like Pvl01 and Pvl06, P. vivax PvP01 and SalI, P. cynomolgi B strain, and P. knowlesi H strain genomes, gene variants were detected and counted using Geneious software  [60]. This allowed the presence/absence of the variants of the different gene families across Plasmodium species to be evaluated. For each gene family, the number of variants identified in the 2 reference genomes Pvl01 and Pvl06 was confirmed by manually checking the presence/absence of these in the other P. vivax-like genotypes obtained using ACT and bamview  [61, 62].
2. 8  [73]. The tree was constructed using the concatenation of the 2,784 orthologous groups that have a final alignment of more than 50 amino acids (among the Pl13sp set of 2,943 groups). RAxML was called using the following options in order to automatically determine the substitution model that best fits the data model and so that 100 bootstraps were performed to assess the tree robustness: "-m PROT-GAMMAAUTO -f a -# 100. " The best amino acid model of substitution identified by RAxML for the dataset (the JTT model with empirical base frequencies JTT + F) was used in the subsequent analyses. The idea behind the Silva method  [29]  for relative age estimation is that the divergence between amino acid sequences in independent lineages is correlated and that the divergence regression slopes of the proteins of a species pair of reference with the divergence of the proteins of other species pairs reflect the relative age of those splits (see Silva and colleagues  [29]  for a detailed description of the method).
Following this method, we obtained, for each of the 2,784 orthologous groups of the Pl13sp set that have a final alignment of more than 50 amino acids and for each species pair, the amino acid sequence divergence d AA through a pairwise comparison using PAML version 4. 7  [74] , with the option "cleandata" set to 1 to remove sites with missing data from the dataset. The sequence divergences d AA were estimated using 4 different models of substitution (JTT, WAG, LG, and Dayhoff) to evaluate their influence on the estimates of the relative ages. An R script from the authors of this method  [29]  allowed the estimation of α, the slopes of the TLS regressions of the divergence of the proteins between every possible species pairs and the reference species pair, with the 95% CI by bootstrapping (n = 10,000 bootstraps).
RelTime estimates relative rates for each branch of the tree without requiring a distribution of rate heterogeneity. The relative rates of 2 sister lineages are estimated assuming that the time to their most recent common ancestor is equal in the presence of contemporaneous sampling, and the rate of their ancestral branch is estimated as the average of their branchspecific relative rates. This framework is applied to subtrees of 3 or 4 taxa following a bottomup strategy, from tips to the root to estimate relative rates and times, relative rates being scaled by setting the lineage relative rate of the ingroop root node to 1 (see Tamura and colleagues  [32] ). RelTime analysis was performed on the concatenation of the alignments of the same 2,784 orthologous groups we used to build the phylogenetic tree, removing sites with missing data (Complete-Deletion option) and using the same substitution model (JTT + F).
Phylogenetic tree of P. vivax and P. vivax-like strains The phylogenetic relationships of the RBPs in the P. cynomolgi-P. knowlesi-P. vivax-P. vivaxlike group of species was reconstructed using a maximum likelihood analysis using RAxML  [73]  with 100 bootstrap replicates. The tree was visualized using Geneious software  [60]. To investigate relationships between the P. vivax and P. vivax-like populations, we constructed a maximum likelihood tree using the filtered variant call set of SNVs limited to the higher allelic frequency genotypes identified within each sample using RAxML and PhyML (using general time-reversible [GTR] models)  [73, 76]. Trees were visualized using Geneious software  [60]. All approaches showed the same final phylogenetic tree described in the "Relationships to worldwide human P.
Analysis of phylogenetic discordance by means of reticulated networks We looked for signatures of introgression and/or ILS by performing a phylogenetic network using SplitsTree 4. 14. 6  [77]  based on the alignment of a portion of the mitochondrial genome containing the cox1 and cytb genes, as in Liu and colleagues  [10]. We included all but 2 (KF618538 and KF618534) samples from Liu and colleagues  [10] , all from Prugnolle and colleagues  [9] , and 3 of our samples with a high-quality-sequenced mitochondrial genome (Pvl08, Pvl09, and Pvl10), and we added P. cynomolgi as the outgroup (GenBank accession number: AB434919. 1). Gaps and monomorphic positions were excluded for the analysis, and the dataset resulted in an alignment of 85 sequences of 127 variable positions. We conducted a reticulate network using the RECOMB 2007  [78]  and the NeighborNet distance transformation methods  [79].
Detection of genes under selection In order to identify genomic regions involved in parasite adaptation to the human host, i. e. , regions under positive selection, we performed branch-site tests. To search for genes that have been subjected to positive selection in the P. vivax lineage alone, after the divergence from P. vivax-like, we used the updated branch-site test of positive selection  [80]  implemented in the package PAML version 4. 4c  [74]. This test detects sites that have undergone positive selection in a specific branch of the phylogenetic tree (foreground branch) using Likelihood Ratio Tests (LRTs) to compare models allowing positive selection or not. The selective pressure is defined as the ratio (ω) of nonsynonymous (i. e. , d N , keeping the amino acid) to synonymous (i. e.
vivax Sal1, P. vivax-like Pvl01, P. knowlesi H strain, and P. cynomolgi B strain were used for this test (i. e. , the 4,056 gene Pv4sp set of orthologous genes). We obtained d N /d S ratio estimates per branch and gene for P. vivax and P. vivax-like lineages alone using Codeml (PAML version 4. 4c  [74] ) with a free-ratio model of evolution. Genes with a significant signal of positive selection in P. vivax only were compared to the ones obtained in P. falciparum from Otto and colleagues  [13]  (S4 Table in Otto and colleagues  [13] ), in order to identify, e. g. , essential proteins for human or vector infection. The data are deposited in the Dryad repository (doi:10. 5061/dryad. 32tm1k4) [81].
Agence Nationale de la Recherche  Jeunes Chercheurs Jeunes Chercheuses http://www. agence-nationale-recherche. fr / Project -ANR-12-JSV7-0006 (grant number  ORIGIN Origin, adaptation and evolution of Plasmodium  falciparum). Received by FP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Agence Nationale de la Recherche Tremplin-ERC  ( TERC3 ) 2017 http://www. agencenationale-recherche. fr / Project -ANR-17-ERC3-0002 (grant number EVAD: Evolutionary history and genetic adaptation of Plasmodium vivax). Received by VR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Laboratoire Mixte International https://www. ird. fr/infos-pratiques/archives/anciens-lmi/lmi-zofac-zoonoses-dans-lesforets-tropicales-humides-d-afrique-centralemodalites-des-transferts-inter-especes-etadaptation-des-pathogenes (grant number ZOFAC: zoonoses dans les forêts tropicales humides d'Afrique centrale: modalites des transferts interespèces et adaptation des pathogènes).
Received by FP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council  Doctoral Training Grant  (grant number  MR/J004111/1 ). Received by GGR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome Trust https://www. genomethics. org/overview. html(grant number  098051  Genome Ethics). Received by GGR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
All sequences have been submitted to the European Nucleotide Archive. The accession numbers of the raw reads are in S1 and S2 Tables. The genome assemblies of Pvl01 and Pvl06 can be found on the Dryad Repository: https://datadryad. org/resource/doi:10. 5061/dryad. 32tm1k4. 2. The two genome assemblies and annotations are available at the following ftp address: ftp://ftp. sanger. ac. uk/pub/ pathogens/Plasmodium/P_vivaxLike/. The dataset used to produce the reference allele frequency distributions are available in the following Dryad repository: doi: 10. 5061/dryad. 32tm1k4. All the other relevant data, alignments, and trees are within the paper and its Supporting Information files.
Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth.
Methods The 3H study will systematically evaluate cardiovascular, nutritional and health-related quality of life (QoL) measures in children on HD and HDF to test the hypothesis that children on HDF have an improved cardiovascular risk profile and growth and nutritional status compared to those on conventional HD. Primary and secondary outcome measures are described in Table  1. We will assess for difference in these outcomes between the two dialysis modalities, and the impact of modifiable risk factors, including clinical and dialysis-related factors, biochemical measures and medications. PROMs will be assessed using established QoL questionnaires as well as dialysis-specific outcomes. This is a registered clinical trial (ClinicalTrials. gov: NCT02063776).
Study design 3H is a multi-centre, non-randomised parallel-arm intervention study carried out by investigators of the International Paediatric Hemodialysis Network (IPHN) Registry and the Cardiovascular Comorbidity in Childhood CKD (4C) Study  [18]. The IPHN prospectively collects detailed data from children on maintenance haemodialysis via an on-line electronic system (www. pedpd. org). The infrastructure, expertise and collaborations of the 4C study consortium, that is performing longitudinal follow-up in a cohort of over 700 children with CKD, is utilised and expanded for clinical and cardiovascular monitoring in 3H. Children were recruited from 28 paediatric dialysis units across Europe and in Toronto, Canada. A minimum follow-up of 12 months was required.
Study organization Patients meeting the inclusion criteria will be enrolled by local investigators. Six investigators serve as regional coordinators and visit study centres annually to perform the vascular scans, collect blood samples and complete data entry. All investigators will be provided with portable equipment for imaging. To ensure optimal reproducibility and quality of the imaging, prior to the start of the study the coordinators will be trained in all the vascular imaging, and blinded assessment of the vascular measures will be performed periodically to determine intra-observer and inter-observer variability. All training of the investigators was performed as part of the 4C study  [19] , and 6-monthly investigator meetings will be held alongside the 4C study meetings to synchronize study activities, discuss results, and exchange experiences.
I -cardiovascular monitoring (baseline and annual intervals) 1. cIMT -High resolution ultrasound of the common carotid artery to measure cIMT (morphology, B-Mode) and elasticity (function, M-Mode) according to the Mannheim cIMT consensus  [20]. The cIMT will be obtained by five averaged measurements on each side using a portable ultrasound device (Acuson P50; Siemens Medical Solutions USA, Inc. ) with integrated digital image evaluation software (Syngo US Workplace; Siemens Medical Solutions USA, Inc. ). As cIMT in children changes with growth, it will be expressed as a SDS using reference values normalized for age, sex and height derived from healthy children  [21]. 2. Aortic pulse wave velocity (PWV) and augmentation index will be measured with the Oscillometric Vicorder device using the distance from the suprasternal notch to the femoral recording point via the umbilicus as path length.
Statistical analysis All analyses has been decided a priori in an analysis plan. Each quantitative outcome will be assessed for normality. cIMT, PWV, 24-h MAP profiles and height will be expressed in SD scores. The co-primary endpoints of mean and standard deviation (or median/interquartile range if appropriate) annualised change between baseline and 1 year in cIMT and height SDS will be calculated, and compared between the HDF and HD cohorts using unpaired t-tests (or the non-parametric equivalent). As data are observational, adjustment for potential confounders (country, age, gender, access type, dialysis vintage) will be made using linear regression. The adjustment for the primary analysis will be made through the construction of propensity scores, representing the likelihood of receipt of HDF (vs HD), based on the pre-specified confounders.