dataesr/scientific-paragraphs-categorization huggingface dataset:
Discussion Patients enrolled in the IXORA-S study were highly representative of those receiving biological treatments in clinical practice throughout Europe. This study demonstrated the rapid and superior efficacy of ixekizumab compared with ustekinumab at week 12, as assessed by PASI 90 response (primary end point), which was maintained through week 24. Similar observations were made for total clearance (PASI 100). Overall, ixekizumab was found to be statistically superior to ustekinumab as early as week 2 and/or week 4 for all key secondary end points. During the first 24 weeks of IXORA-S, both drugs were generally well tolerated. These data indicate that ixekizumab can provide a faster and greater level of improvement than ustekinumab in patients with plaque psoriasis, while maintaining a safety profile consistent with previous reports.
Ct Reference and Clinical Samples A total of 323 reference and clinical samples were analyzed that included 58 endocervical samples from St. Petersburg, 60 additional endocervical samples from Amsterdam and eight endocervical samples from Boston, Massachusetts; 265 were already in the MLST database 1  including the 20 reference strains: A/SA-1, A/HAR13, B/TW5/OT, Ba/Apache2, C/TW3/OT, D/UW3/Cx, Da/TW-448, E/Bour, F/IC-Cal3, G/UW57/Cx, H/UW4/Cx, I/UW12/Ur, Ia/UW202, J/UW36/Cx, Ja/UW92, K/UW36/Cx, L 1 /440, L 2 /434, L 2a /UW396, L 3 /404. ompA Genotyping and MLST Analysis Genomic DNA was purified from clinical isolates and ompA genotyped as described previously  (Dean et al. , 2009; Batteiger et al. , 2014). Only the samples from St. Petersburg were provided as swabs; DNA was extracted and purified for these samples using our protocol as described in  Joseph et al.
(2014). MLST analysis examined seven housekeeping genes: glyA, mdhC, pdhA, yhbG, pykF, lysS, and leuS, with primers as described  (Dean et al. , 2009)  (Supplementary Table  1 ). All seven housekeeping genes were amplified and sequenced as described  (Batteiger et al. , 2014). A consensus sequence was created from the forward and reverse sequence. The genes for each of the St. Petersburg, Amsterdam and Boston samples were each concatenated and queried against the 265 samples in the MLST database in addition to including these samples in the database. Allelic numbers and STs were assigned based on this query as described previously  (Batteiger et al. , 2014).
Phylogenetic Analysis and Strain Clustering Using the concatenated sequences, dataset strain clustering and Single Nucleotide Polymorphism (SNP) analyses were performed as described  (Batteiger et al. , 2014). Briefly, this included visualizing clusters of related STs and non-related STs using eBURST 2   (Feil et al. , 2004). Founder STs were identified by the highest number of single locus variants (SLV) branching from that particular ST (i. e. , the clonal ancestor that diversifies into other STs). Clonal complexes generated by eBURST were defined as a group of STs separated by one SLV. Phylogenetic trees were created by Maximum likelihood using the Symmetric+GI model, which provided the best fit for the data, in the R package phangorn  (Schliep, 2010)  to analyze the nucleotide sequence variation between the seven MLST loci for each ST.
Tree nodes were verified with 1,000 bootstrap replicates. Alternative evolutionary pathways, such as horizontal gene transfer, were analyzed with SplitsTree 3  using the splits decomposition method as described  (Dean et al. , 2009; Tamura et al. , 2013). In addition, the sequence for each of the seven MLST loci for a sample were compared across the dataset and to the ompA genotype of the same sample to determine evidence for putative recombination.
PROC FREQ in SAS was used to identify SNPs associated with disease phenotype and Haplotype as described previously  (Dean et al. , 2009 ). Levene's test evaluated the variance across the dataset of the 323 samples. The Classification Index was used to determine significance of each SNP with a disease phenotype where a p-value of <0. 05 was considered significant. DnaSP v5. 10 (Librado and Rozas, 2009) was used to calculate nucleotide (nt) and haplotype (hd) to determine the genetic diversity and differentiation for regional subgroups on the concatenated sequences of the seven MLST genes. DnaSP considers the frequency of variants (STs) present in a population and also genetic distances that separate these variants from each other. Genetic population differentiation between regional subgroups was assessed using the pairwise fixation index (Fst) in Arlequin v3.
ST and ompA Distributions For the 323 samples, 84 unique STs were identified (Supplementary Table  3 ). STs novel to the dataset were numbered consecutively in order of identification. Of those 84, 57 (67. 9%) were singletons, with a relatively even distribution by geographic region (excluding Asia and Africa where the sample sizes were very small) with a higher percentage of singletons in Europe that was not significantly different (Table  2 ; p = 0. 08). Table  2  also shows that the percentage of unique STs per region was highly similar. However, the ST/sample ratio was significantly greater for Russian than for European and American samples (p < 0. 009). There were also significant differences in the distribution of STs (Table  3 ). Dutch females (n = 79) were significantly more likely to be infected with ST23 (p = 0.
032; 95% CI: 1-23) and ST34 (p = 0. 02; 95% CI: 1. 1-25) compared to Russian females (n = 58) and with ST19 (p = 0. 001; 95% CI: 1. 7-34. 7) compared to American females (n = 108). Supplementary Table  4  shows the distribution of STs by geographic region. There were 26 ompA genotypes observed in the dataset resulting in a 3. 23 lower resolution than for STs. Excluding the STDs samples from South Africa, all samples available from Asia and Africa were from trachoma patients; 1 (7. 1%) of 14 was a urogenital Da ompA genotype (ST 37) in Asia while 1 (5. 9%) of 17 was a urogenital E genotype (ST 39) in Africa. ompA genotype E (n = 72) was the most prevalent and associated with 18 STs with an ST to sample ratio of 0. 25 (Supplementary Table  3 ). The distribution for the remaining ompA genotypes in descending order was G (38; 16 STs; ratio: 0.
001). In the Americas, ompA genotype Ia was significantly more prevalent than the other regions (p = 0. 001). In comparing female STD cohorts, Russian women were significantly more likely to be infected with E and G (p = 0. 001 and 0. 026, respectively) while Dutch women were significantly more likely to be infected with D and I (p = 0. 026 and 0. 002, respectively). Simpson's Discriminatory Index was 0. 98 (95% CI 0. 97-0. 99) for MLST and 0. 70 (95% CI 0. 67-0. 73) for ompA genotyping. Based on DnaSP, nucleotide diversity was lower in Russia (Pi = 0. 00216) compared to Netherlands (Pi = 0. 00321) and North America (Pi = 0. 00294) (Table  4 ). However, Netherlands and North American datasets contained isolates from men and LGV samples. The phylogenetically disparate LGV samples appeared to contribute substantially to nucleotide diversity; nucleotide diversity dropped from 0.
00250 to 0. 00196 in Dutch women when the four LGV isolates were removed. When comparing non-LGV isolates from women in these regions, Russian women had the highest nucleotide diversity (Pi = 0. 00216), followed by North American women (Pi = 0. 00210), and Dutch women (Pi = 0. 00196). Assessing population differentiation between regional subgroups by Fst revealed significant differences between most regional subgroup pairwise comparisons (Table  5 ). African and Asian subgroups exhibited high Fst values in all comparisons, indicating those regions were distinct from others in the dataset. This is not surprising given the small sample size and the fact that these samples are from two distinct trachoma populations. Though Western Europe was significantly different from all subgroups, the Russia and Americas subgroups were not significantly different by Fst.
However, this could be attributed to the higher LGV representation in the Western European samples (15. 5%) in comparison to the American samples (7. 3%), and Russian samples (0%). Concordantly, when LGV samples were removed from the Western European dataset, Western Europe was no longer significantly different from Russia (Table  5 ). When evaluating only women without LGV from the Netherlands, Russia, and North America, the Russian women were not significantly different from the American and Netherlands women (Supplementary Table  8 ).
8%) from the Netherlands. While ompA genotypes were generally consistent across samples of the same ST, many cases of recombinant strains were observed. For example, ST19 (n = 40) was primarily associated with ompA genotype G (37. 5%) but eight different ompA genotypes (B, D, E, G, H, I, J, K) were also associated with this ST. The majority of these samples were from St. Petersburg and Amsterdam (Supplementary Table  3 ). ST23 (n = 32) was also associated with eight ompA genotypes (B, D, G, H, I, Ia, J, K) but the most frequent was Ia (47%). In contrast, the most geographically prevalent ST was ST39 (n = 45) where 95% were associated with ompA genotypes E. There were also 24 singletons that were recombinants (Table  6 ). Table  7  shows the ompA genotype, ST and allelic SNPs, if present, associated with each of the eight Boston samples added to the dataset.
Under the column denoted ST sequence homology are the Ct ompA genotype sequences to which the sequences of the seven MLST genes are identical. For example, sample J/259b  has four SNPs that are different from the sequences of the seven genes for reference and clinical J strains in the database. These SNPs are identical to the sequences of strains G and K, which suggests that this sample is a recombinant between J and G or K strains. Another example is sample D/256b; the ompA genotype is D but the MLST sequences of the seven genes are identical to The numbers represent the ST. The tree was constructed using the matrix of pairwise differences between the 84 ST concatenated nucleotide sequences for the seven MLST loci using the maximum composite likelihood method for estimating genetic distances.
Only bootstrap values (1,000 replicates) of >70% are shown at branch points in the tree. STs (shaded gray) are singletons. Orange, Africa; red, Asia; yellow, Americas; blue, Russia; green, Western Europe. Scale bar indicates number of substitutions per site. reference and clinical F strains in the database. Therefore, it is a recombinant between D and F. Five (62. 5%) of the eight Boston samples were putative recombinants. Supplementary Table  5  shows similar data for the 60 new samples from Amsterdam. For the Amsterdam samples, 43 (54. 4%) of 79 samples were recombinants. Likewise, Supplementary  The non-invasive group includes clinical Ja strains that are recombinants of E and F strains. There are 14 SNPs that are specific for the LGV disease group, and each SNP independently identifies this group and Haplotype.
A significantly higher ST to sample ratio of 0. 45 was identified for Russian compared to European and American samples (p < 0. 009). This was not explained by the number of STs unique to a region as the percentages were relatively uniform across the geographies (Table  2 ). However, Russian women had the highest nucleotide diversity (Pi = 0. 00216), followed by North American women (Pi = 0. 00210), and Dutch women (Pi = 0. 00196), excluding LGV strains that are present only in the female Dutch population and would therefore skew the data. There are no males in the Russian dataset and therefore only women were evaluated here for the three locals. However, when assessing population differentiation for women from the Netherlands, Russia, and North America, excluding those with LGV, there were no significant differences (Supplementary Table  8 ).
, 1998; Dean et al. , 2009). We performed ompA genotyping on all samples in the database and, for ST23, the samples comprised Ia, B, D, G, H, I, J, and K genotypes while for ST34 they included genotypes F, D, D2, E, J, and Ja (Supplementary Table  3 ). The high number of ompA genotypes for these two STs suggests a high rate of recombination. For example, the sequences of the seven MLST genes matched those of reference strain Ia/UW202 for 47% of the ST23 samples where the ompA genotype was also Ia. However, the remaining samples that also matched the seven MLST Ia/UW202 sequences had B, D, G, H, I, J, and K ompA genotypes, indicating a mismatch between the MLST and ompA sequences, providing evidence for recombination (Supplementary Table  3 ). Similarly, STs such as 15, 19, and 34 had numerous samples, some of which were putative recombinants.
, 2016). Of course, with WGS, many additional genes have been found to be involved in recombination  (Harris et al. , 2012; Joseph et al. , 2012; Hadfield et al. , 2017). To confirm putative recombinants, we had described that the sequences of the seven MLST genes were individually aligned to the respective gene for all samples in the database and compared these results to the ompA genotype of the same sample. For example, Table  7  shows the five putative recombinants among the eight Boston samples. Sample D/256b had an ompA genotype of D but the seven MLST sequences were an exact match to the seven sequences of F. In some cases, one or more of the seven genes matched two different strains as was the case for samples J/253b and J/259b. Other examples of recombinants are shown in Supplementary Tables  6  and 7  for the Dutch and Russian samples, respectively.
In addition, Splitstree analysis was performed and revealed ancillary evidence for a network structure consistent with homologous recombination Bold denotes putative recombinant. * The seven ST genes of the sample have the highest homology to the seven genes of the strain that has the ompA genotype denoted in the column (e. g. , for sample D/256b that has a D ompA genotype, the seven ST genes were identical to the seven genes of F strains in the database where the ompA genotype was also F for those strains). LGV, lymphogranuloma venereum. * p < 0. 01. (Figure  2 ). While these data confirm the recombinant nature of the samples, it is likely that there are other genetic regions that have undergone recombination and, therefore, it is not possible to determine the extent of genetic exchange unless WGS is performed  (Joseph et al.
Indeed, rates of Ct mixed infections as high as 6 to 16% have been reported among men who have sex with men and heterosexual populations, respectively, in Europe, including the Netherlands  (Quint et al. , 2011; Rodriguez-Dominguez et al. , 2015). The most geographically prevalent ST was 39 with 45 samples, 95% of which had an ompA genotype of E; there were only two recombinants in this ST: one from Boston with a D ompA genotype and one from St. Petersburg with a G genotype. E genotypes are known to be the most globally prevalent  (Lysén et al. , 2004; Millman et al. , 2004; Spaargaren et al. , 2004; Lee et al. , 2006; Gharsallah et al. , 2016)  and the least recombinogenic based on whole genome sequencing  (Joseph et al. , 2011 (Joseph et al. , , 2012)). In our dataset, there were 72 E genotypes with an ST to sample ratio of 0.
25; only the F genotype, the 4th most prevalent genotype with 30 samples, had a lower ratio at 0. 17. The lower ratios indicate greater fitness as these strains are prevalent worldwide and have fewer allelic variants that resolve into fewer STs. This is borne out by the fact that only eight (11%) of the 72 E genotypes and 0 of the 30 F genotypes were recombinants (Supplementary Table  3 ). A recent genome study that included 149 E strains supports our conclusions  (Hadfield et al. , 2017). Genotype D was also highly prevalent but had a much higher ratio at 0. 48, and 29 (88%) of 33 samples were recombinants. We previously found that phylogeny based on MLST resolved the STs along disease phenotype demarcations. As samples have been added to the database, the phenotype resolution has increased to include the LGV phenotype, denoted as clonal cluster-D (CC-D; Figure  1 ).
Similarly, the tree shows the three main clusters with the trachoma STs as a Subcluster of Cluster I, which resembles those of other reports  (Herrmann et al. , 2015). To determine whether the phenotypic groups could be more finely discriminated, we analyzed the database for SNPs that independently or together would identify a phenotype. As in our previous studies  (Dean et al. , 2009; Batteiger et al. , 2014) , specific SNPs correlated with LGV, non-invasive urogenital disease and trachoma. Haplotype 2, which included the noninvasive urogenital disease group required exclusion of strains that were recombinants, specifically D genotypes.
Chemical and Physical Parameters Temperature, salinity, and conductivity were measured using a in situ multi-parameter probe (TetraCon 325, WTW, Germany). To determine the SPM concentration, the water was filtered through preweighed 0. 45-µm pore-size filters (Whatman GF/F, Sigma-Aldrich). After filtration, the filters were rinsed with distilled water (10% filtered volume) to remove the salt and dried for 48 h at 50 • C before being weighed again to determine the total SPM concentration. Rainfall was extracted from Méteo-France database 2. River flow was extracted from the GIP-SA database 3 , as was the flow rate.
DNA Extraction and PCR Amplification Cell suspensions were prepared with two or three colonies in 200 µL of sterile water and total bacterial DNA was extracted by boiling (10 min at 94 • C). All presumptive Aeromonas strains were tested and identified at the species level by amplification and  ; e CFU. g -1 (wet weight); f count below the detection threshold; NA: not analyzed; NS: not sampled. sequencing of housekeeping genes. PCRs were performed with specific primers targeting the gyrB gene  (Yáñez et al. , 2003)  and the radA gene  (Roger et al. , 2012) , as previously described. The PCR products were separated in 1. 5% agarose gel in 0. 5× TBE buffer. The products were sequenced using forward amplification primers in an ABI 3730XL automatic sequencer (Beckman Coulter Genomics). Membership in the genus Aeromonas was checked by comparison with the NCBI database using the Basic Local Alignment Search Tool (BLAST 4  ).
Phylogenetic Analysis Phylogenetic analysis was performed as previously described by  Roger et al. (2012). Briefly, gene sequences were codon-aligned using the ClustalW application within the Bioedit Sequence Alignment Editor. Phylogenetic analyses were performed for each of the two gene sequences and for a manually concatenated sequence. Gaps in concatenated sequences were deleted with Bioedit. The sequences were converted to Phylip format using the EMBOSS Seqret online program 5. A maximum likelihood (ML) method-based phylogenetic tree was reconstructed using evolutionary distance analyzed with the PhyML v3. 1 software using GTR, with a gamma distribution parameter estimated from the dataset and invariant sites as a substitution model. ML bootstrap support was calculated after 100 reiterations.
Statistical Analysis The chi-squared test of the Fisher exact test was performed to compare the antimicrobial profiles; the Pearson coefficient was used to measure the degree of linear correlation between abundance of Aeromonas in water and fluid mud; the Student's t-test was used to compare the abundance of Aeromonas inside the water column. All data analyses were performed with XLSTAT (XLSTAT, Boston, MA, United States V2016. 3).
Surface water (-50 cm below the surface) and fluid mud were sampled in the mouth of the Seine Estuary at Tancarville site (N 49 • 28 30. 26 E 0 • 27 48. 65 ). a Average daily flow rate (GIP Seine-Aval database); b cumulated rainfall 7 days before the sampling (Météo France database); c Suspended Particulate Matter (wet weight); d CFU. 100 mL -1.
ACKNOWLEDGMENTS The authors wish to thank:  Florian Van Dooren  and  Michel Simon  for their technical assistances, the SAUR company that gave us access to the  WWTP of Tancarville, Pr. A. Andremont  and  N. Grall  ( INSERM, IAME, UMR 1137 ) for the identification of presumptive Aeromonas using MALDI-TOF mass spectrometry and  Pr Ingrid Padilla  ( Puerto Rico University, United States ) for the critical review of the manuscript.
NS Surface water (-50 cm below the surface) and fluid mud were sampled in the mouth of the Seine Estuary at Tancarville site (N 49 • 28 30. 26 E 0 • 27 48. 65 ). a Average daily flow rate (GIP Seine-Aval database); b cumulated rainfall 7 days before the sampling (Météo France database); c Suspended Particulate Matter (wet weight); d CFU. 100 mL -1.
Briefly, all materials were equilibrated at room temperature prior to use. For initial detection of specific antibodies, serum samples were diluted 1 to 100 with sample diluent as indicated in the manufacturer's instructions. Limited cross reactivity data are available for the kits used. Cutoff for positivity was 11. 0 standard units. Statistical analysis used Chi-square or Fisher's exact tests for categorical data, and Kruskal-Wallis tests for quantitative data. Effect of age, sex and disease status on positive C. trachomatis serology was tested on IgG positivity, IgA positivity and positivity of either IgA or IgG. Additional comparisons were done within the families' studies, among controls, healthy relatives and CD patients; within sporadic cases, between CD and ulcerative colitis (UC) patients.
Selection of eligible studies This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria  [13]. The eligible studies were obtained by searching online databases, MEDLINE and EMBASE. The following keywords were used for searching: (''inflammatory bowel disease'' OR ''Crohn's disease" OR "ulcerative colitis") AND ("polymorphism * "OR "variant") AND (''protein tyrosine phosphatase nonreceptor'' OR "PTPN22" OR "lymphoid protein tyrosine phosphatase"). The most recent research was performed on April 30th 2016, and there was no limitation on the research. The references of reviews and retrieved articles were also searched simultaneously to find additional eligible studies. Research was performed using the Entrez interface of the National Center for Biotechnology Information (ncbi) from the terminal of a Linux station (ubuntu 14.
Data extraction Relevant information from the articles were extracted from the studies independently by the first (AH) and second (CC) authors. Disagreements were resolved through discussion to reach consensus or were adjudicated by a third author. If genotype information was lacking, we tried to contact the corresponding authors in order to obtain the required data. If they did not provide data, those studies were excluded from our review. General characteristics (e. g. demography, genotyping method) of the included studies were extracted. We extracted the following information from each included study: first author's name, publication year, sample size, source of controls, ethnicity, genotyping method, matching variables of controls with cases, age, sex distribution, and counts of alleles and genotypes in both cases and controls.
The random effects model is best used in the presence of significant between-study heterogeneity  [16]. We quantified the effect of heterogeneity by using the recently developed I 2 measure, where I 2 = 100% × (Q -df)/Q, where df is degrees of freedom  [17]. The I 2 measure ranges between 0% and 100% and represents the proportion of inter-study variability attributable to heterogeneity rather than chance. I 2 values of 25%, 50%, and 75% were defined as low, moderate, and high estimates, respectively. All statistical analyses were performed using the general package for meta-analysis (version 4. 6-0, depends on R≥2. 9. 1).