dataesr/scientific-paragraphs-categorization huggingface dataset:
By contrast, in LMICs in south/southeast Asia, the odds of TDR remained unchanged following ARV scale-up. In Latin America/Caribbean, North America, Europe, and upper-income Asian countries, the odds of TDR have increased by around 1. 10-fold per year since 1995, mainly as a result of increased NNRTI resistance. Four NNRTI-associated and 16 NRTI-associated SDRMs accounted for most NNRTI-and NRTI-associated TDR, respectively, in all regions. Notably, in sub-Saharan Africa and south/southeast Asia, most of the NNRTI-associated SDRMs detected were associated with high-level resistance to nevirapine or efavirenz. Finally, the researchers report that 95% of TDR viruses in sub-Saharan Africa and south/southeast Asia were unrelated and had therefore arisen independently. What Do These Findings Mean? Because many drug-resistance mutations reduce HIV's fitness and tend to be lost rapidly in individuals not exposed to ARV therapy, differences among the datasets used in this meta-analysis with respect to how long each ARV-naïve patient had been infected with HIV before virus sampling may limit the accuracy of these findings.
Additional Information Please access these websites via the online version of this summary at http://dx. doi. org/10. 1371/journal. pmed. 1001810. • Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS • NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS • Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on antiretroviral drugs and on universal access to ARV therapy; Avert also provides personal stories about living with HIV/AIDS • The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of antiretroviral therapy for treating and preventing HIV infection • The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy • The Stanford University HIV Drug Resistance Database includes information about surveillance drug-resistant mutations (SDRMs) and an interactive map displaying HIV drug resistance in ARV-naïve populations.
Acknowledgments This work was supported by grants from:  SIRIC-CARPEM  and  ARC  no. PJA 20141201954  to LR and  ANR Genopath 2009-2012 09geno03101I ,  APHP-PHRC AOM08198  and  EU   FP7  grant  2012-305608  (EURenOmics) to VF-B and by  INSERM. The shapes of the cells used in this review are inspired by http://smart. servier. fr/servier-medical-art.
Obtained data were normalized to hematocrit values in the periphery and coronary blood, respectively. To determine the specifi city of the MP-bound IgM, an ELISAbased immunocompetition assay using native LDL, Cu-OxLDL, or MDA-LDL as competitors was performed. MP lysates (1:50) were diluted in TBS/BSA and mixed 1:1 with 50 µg/ml of native LDL, Cu-OxLDL, or MDA-LDL, and binding to coated MDA-LDL was measured as described above.
Flow cytometric analysis of platelets Purifi ed platelets were stained with 10 µg/ml of LR04 or an isotype control antibody (MM-30; Biolegend) for 30 min at 4°C. After washing in fi ltered PBS + 0. 5% BSA, cells were pelleted at 500 g and incubated with 0. 25 µg/ml of anti-IgM APC (II/41; eBiosciences) for 20 min in darkness at 4°C. Cells were washed again and samples were acquired on a FACS Calibur (Becton Dickinson), and data were analyzed using Flow Jo software (Treestar). 3). Moreover, costaining of circulating MPs with LR04 and T15/E06 antibodies revealed that PC epitopes are nearly exclusively present on MDA-carrying MPs (supplementary Fig. 4 ). To rule out that the presence of OSEs was due to ex vivo oxidation, BHT was added to the plasma, in addition to EDTA, before isolating MPs, as addition of BHT to plasma has been shown to prevent ex vivo oxidation of LDL  ( 33 ).
Statistical analyses Statistical analyses were performed using Graph Pad Prism 5 for Windows (Graph Pad Software). Two data groups were compared using Student's unpaired or paired t -test. To analyze multiple group data, either one-way or two-way ANOVA tests followed by Bonferroni's multiple comparison tests were performed as appropriate. For correlation analysis, the Pearson's test was used. Data are presented as mean ± SEM. A P value of <0. 05 was considered signifi cant.
This work was supported by the  SFB Lipotox F30 of the Austrian Science Fund , a  Bridge grant  from the  Austrian Research Promotion agency  (C. J. B. ),  National Institutes of Health  Grant  088093  (J. L. W. , S. T. ), and the  Fondation Leducq  (C. J. B. , C. M. B. , S. T. , J. L. W. ). J. L. Sanofi  and  Genzyme , has research grants from  Regeneron , and is a part-time employee of ISIS Pharmaceuticals.
e. before substitution programs with methadone and buprenorphine were launched in France. Data on the HIV-1 transmission group and date of HIV-1 diagnosis were collected from the databases of the four clinical centres. The clinical charts of potentially eligible patients were then reviewed by the same investigator to check for injection drug history (including the date of first i. v. drug use). The study was restricted to individuals who did not have HIV-1-seropositive sexual partners at the time of HIV diagnosis and who were not transfusion recipients. The Scientific Review Board of Bicêtre Hospital approved the study and all the patients gave their written informed consent to participate. Sequencing of the CLDN6, CLDN9, OCLN and SCARB1 genes DNA was extracted from peripheral blood mononuclear cells with the Blood and Cell Culture DNA maxi kit (Qiagen).
Bioinformatics analyses Polyphen and SIFT (Sort Intolerant From Tolerant) are sequence homology based tools that predicts whether an amino acid substitution in a protein will have a phenotypic effect. These prediction softwares are based on the principle that protein evolution is correlated with protein function. Positions important for function should be conserved in an alignment of the protein family, whereas unimportant positions should appear diverse in an alignment. This software will predict which mutants may have a phenotypic effect. SIFT takes a query sequence or a SNP and uses multiple alignment information to predict tolerated (meaning no predicted effect on structure or protein function) and deleterious (that can render the resulting protein nonfunctional or defective) substitutions for every position of the query sequence or for the SNP.
From a query sequence SIFT searches for similar sequences, chooses closely related sequences that may share similar function to the query sequence, obtains the alignment of these chosen sequences, and calculates normalized probabilities for all possible substitutions from the alignment. Positions with normalized probabilities less than 0. 05 are predicted to be deleterious, those greater than or equal to 0. 05 are predicted to be tolerated (http://sift. jcvi. org/). Polyphen-2 (http://genetics. bwh. harvard. edu/pph2/) predicts the functional significance of an allele replacement from its individual features using HumDIv and HumVar datasets (compiled human disease-causing mutations from the UniProtKB database). For a mutation, Poly-Phen-2 calculates probability that this mutation is damaging and reports estimates of false positive rate (the chance that the mutation is classified as damaging when it is in fact non-damaging) and true positive rate (the chance that the mutation is classified as damaging when it is indeed damaging), mutation is also appraised qualitatively, as benign (correspond to tolerated for SIFT), possibly damaging, or probably damaging (damaging corresponds to deleterious for SIFT).
In our previous study of the CLDN1 gene, we identified no specific coding variants in the case population  [18]. Here, direct genomic sequencing of the whole coding region and adjacent intron-exon junctions of the CLDN6, CLDN9, OCLN and SCARB1 genes in the case and   However, one SNP, rs149605777 (Fig  2 ), corresponding to a c. 626G>A heterozygous coding variant, was found only in the HIV+HCV-case population (G>A n = 1). This variant leads to a missense Arg209Gln (R209Q) change in the C-terminal cytosolic tail of CLDN6, with a nonattributed MAF (minor allele frequency) in the NCBI database. Prediction tools (PolyPhen 2 and SIFT) showed that this mutation is possibly damaging or tolerated (scores of 0. 533 with PolyPhen and 0. 43 with SIFT). Human Splicing Finder (HSF) software showed that this c.
626G>A substitution potentially creates a splice acceptor site. However, sequencing of cDNAs derived from the patient's blood cell mRNA showed no evidence of splicing in vivo (see Materials and Methods). In the CLDN9 gene, we identified SNPs already described in databases (Fig  2 ). There was no statistically significant difference between the control and case populations. In the OCLN gene, we identified several SNPs and also one rare heterozygous variant, exclusively in the case population (Fig  2 ). This rare rs147125035 variant was present in only one HIV+HCV-patient and corresponded to a missense c. 70C>G substitution with a MAF frequency of 0. 006. It leads to a Pro24Ala (P24A) change (Fig 2 ) in the N-terminus of OCLN. This variant is predicted to be potentially damaging or deleterious (scores of 1 with PolyPhen and 0.
12 with SIFT). Interestingly, this rare variant was found in the case patient harboring the CLDN6 mutation described above. HSF software identified no splice site for this variant. Both mutated residues in CLDN6 and OCLN are highly conserved in different species. We also identified two variants of the SCARB1 gene, both in another case patient (Fig  2 ): rs5891 (MAF: 0. 007) and rs372663606 (no attributed MAF in NCBI), corresponding to heterozygous c. 403G>A missense (leading to a p. Val135Ile change) and c. 1056G>A synonymous (p. Pro352) substitutions, respectively. HSF software identified no splice site for this variant. The c. 403G>A missense substitution is predicted to be benign/tolerated (scores of 0. 322 with Poly-Phen and 0. 5 with SIFT). Thus, we found that 2 of the 22 HIV+HCV-IDU case patients displayed specific mutations or variants in HCV cellular receptors.
We found variants in CLDN6, OCLN and SCARB1, solely in the cases (2/22, 18%). The corresponding mutations affected residues that are highly conserved in various species and are thus likely to be damaging. Two mutations had no reported database frequency, while the other two variants were rare and not found in the control population. Interestingly, the same case patient harbored one heterozygous mutation in CLDN6, together with one rare heterozygous mutation in OCLN, both of which were likely damaging and involved residues highly conserved in different species. The probability of finding both variants in the same case patient was extremely low. Another case patient harbored two mutations in SCARB1, but prediction tools suggested that they were unlikely to have functional consequences. Once again, the likelihood of the two variants occurring in the same patient was extremely low.
Acknowledgments We thank  Olivier Alibeu  for technical assistance. This work was supported by the  French National Agency for Research on AIDS and Viral Hepatitis (ANRS)  (grants  ANRS AO-1-2008  and  ANRS AO-2-2013 ) and by grants from  Roche  laboratories ( Dr. Alexandrina Pinta ) and  Janssen  laboratories ( Dr. Rima Lahoulou ). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
Acknowledgements The authors would like to thank  Norbert Mencke ,  Lourdes Mottier  and  David McGahie , and the kind support of  Bayer Animal Health GmbH and Virbac Group. The authors would like to acknowledge scientists and veterinarians who have advanced the understanding of FeL. Publication of this manuscript has been sponsored by  Bayer Animal Health GmbH. All authors are members of LeishVet (www. leishvet. org). LeishVet address:  Facultad de Veterinaria, Dpto. Sanidad Animal, Avda. Puerta de Hierro s/n 28040 Madrid ,  Universidad Complutense de Madrid, Spain. E-mail: leishvet@ucm. es.
If the evidence is IDA, then the property was directly observed for a live isolate by one of the authors or an expert mentioned in the acknowledgements  (Table  1 ) was isolated in December 2013 by aerobic cultivation on a culture medium consisting of a Columbia broth culture medium (Sigma-Aldrich, Saint-Quentin Fallavier, France) modified by the addtion of 100 g/L of NaCl with a pH adjusted to 7. 5. O. picturae strain S1 had a 16S rRNA sequence similarity of 99. 8 % with the The strains and their corresponding GenBank accession numbers for 16S rRNA genes are (type = T ): Oceanobacillus indicireducens strain A21 T , NR_113330, Oceanobacillus chironomi strain T3944D T , NR_043700, Oceanobacillus caeni strain S-11 T , NR_041533, Oceanobacillus chungangensis strain CAU 1051 T , NR_109672, Oceanobacillus picturae strain R-5321 T , NR_028952, Oceanobacillus manasiensis strain YD3-56 T , NR_116624, Oceanobacillus kapialis strain SSK2-2 T , NR-112740, Oceanobacillus polygoni strain SA9 T , NR_114348, Oceanobacillus profundus strain CL-MP28 T , NR_043778, Oceanobacillus kimchii strain X50 T , NR_117544, Oceanobacillus iheyensis strain HTE831 T , NR_075027, Oceanobacillus iheyensis strain HTE831 T , NR_028001, Oceanobacillus oncorhynchi subsp.
incalanensis strain 20AG T , NR_042257, Oceanobacillus locisalsi strain CHL-21 T , NR_116461, Oceanobacillus sojae strain Y27 T , NR_112845 and Oceanobacillus neutriphilus strain A1g T , NR_116424. Phylogeny pipeline  [28]  was used, wherein sequences were aligned using MUSCLE  [29]  alignment curation by Gblocks  [30]  and construction of phylogenic tree performed using PhyML  [31]. Numbers at the nodes are bootstrap values obtained by repeating the analysis 100 times. The scale bar represents a 2 % nucleotides sequences divergence Fig. 2  Gram staining of Oceanobacillus picturae strain S1 T Fig. 3  Transmission electron microscopy of Oceanobacillus picturae strain S1 T , using a Morgani 268D (Philips) at an operating voltage of 60 kV. The scale bar represents 500 nm reference strain O. picturae strain LMG19492 T (Genbank accession number NR_028952) (Fig.
All spectra were recorded in the positive linear mode for the mass range of 2000 to 20,000 Da (parameter settings: ion source 1 (ISI), 20 kV; IS2, 18. 5 kV; lens, 7 kV). A spectrum was obtained after 675 shots with variable laser power. The time of acquisition was between 30 s and 1 min per spot. The twelve spectra of strain S1 were imported into the MALDI BioTyper software (version 2. 0, Bruker) and analyzed by standard pattern matching (with default parameter settings) against the main spectra of over 4108 bacteria including the spectra from the most closely related species including Oceanobacillus oncorhynchi CIP108867T, Oceanobacillus profundus CIP 109535T, Oceanobacillus chironomi CIP 109536T, Oceanobacillus iheyensis CIP 107618T, and Oceanobacillus oncorhynchi subsp. incaldanensis CIP 109235T, and Oceanobacillus sojae.
In addition to these validly published species, we compared the O. picturae spectrum with spectra of Oceanobacillus massiliensis strain N'Diop and 'Oceanobacillus manasiensis' (HG931336). The resulting score was > 2, matching with Oceanobacillus picturae CIP 108264 T. The identification method included the m/z from 3000 to 15,000 Da. For every spectrum, a maximum of 100 peaks were compared with spectra in the database. We added the spectrum from strain S1 T to our database (Fig. 4 ).
Genome project history The O. picturae genome was sequenced as part of a culturomics study aiming to isolate all bacterial species colonizing the human gut  [1]  (Table  2 ). To the best of our knowledge, O. picturae represent the fifth genome sequenced into the Oceanobacillus genus and the first genome of O. picturae. The genome accession number is CCAX00000000 and consists of 5 contigs without gaps. Table  3  shows the project information and its association with MIGS version 2. 0 compliance.
2 % (9,590,000 clusters). Within this run, the index representation for O. picturae was determined to be 11. 16 %. Illumina reads were trimmed using Trimmomatic  [32] , then assembled through Spades software  [33, 34]. Contigs obtained were combined together by SSpace  [35]  and Opera software v1. 2  [36]  helped by GapFiller V1. 10 [37]  to reduce the set. Some manual refinements using CLC Genomics v7 software Fig. 5  Circular representation of the Oceanobacillus picturae genome. Circles from the center to the outside: GC screw (green/purple), GC content (black), tRNA (dark red), rRNA (purple), tmRNA (blue), miscellaneous RNA (beige) on forward strand, genes on forward strand colored by COGs categories, scaffolds in alternative grays, genes on reverse strand colored by COGs, tRNA (dark red), rRNA (purple), tmRNA (blue), miscellaneous RNA (beige) on reverse strand cCLC bio, Aarhus, Denmark) and homemade tools improved the genome.
Genome annotation Non-coding genes and miscellaneous features were predicted using RNAmmer  [38] , ARAGORN  [39] , Rfam  [40] , PFAM  [41] , Infernal  [42]. Coding DNA sequences (CDSs) were predicted using Prodigal  [43]  and functional annotation was achieved using BLAST+  [44]  and HMMER3  [45]  against the UniProtKB database  [46].
Genome properties The genome of Oceanobacillus picturae contained 3,675,175 bp with a G + C content of 39. 15 % (Fig. 5 , Tables  3  and 4 ). The genome was shown to encode at least 157 predicted RNA including 14 rRNA, 31 tRNA, 1 tmRNA and 111 miscellaneous RNA. In addition, 3666 genes were identified, representing a coding capacity of 3,125,691 bp (coding percentage: 85. 05 %). Among these genes, 269 (7. 34 %) were found as putative proteins and  The total is based on the total number of protein coding genes in the annotated genome 891 (24. 3 %) were assigned as hypothetical proteins. Moreover, 3595 genes matched at least one sequence in Clusters of Orthologous Groups database  [47]  with BLASTP default parameters. The properties and the statistics of the genome are summarized in Tables  4  and 5.
Acknowledgments This project was funded by the  Deanship of Scientific Research (DSR) ,  King Abdulaziz University, Jeddah , under grant no. (HiCi- 1434-140-30 ). The authors therefore acknowledge with thanks the DSR technical and financial support. We thank  Karolina Griffiths  for English reviewing. Author details 1  Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ,  UM 63 ,  CNRS 7278 , L' Institut de Recherche pour le Développement 198 ,  Inserm 1095, Institut Hospitalo-Universitaire Méditerranée-Infection, Faculté de Médecine, Aix-Marseille Université , 27  Boulevard Jean Moulin , 13385  Marseille Cedex  5, France. 2  Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah ,  Saudi Arabia.
Identification of DNA methylation changes in psoriatic epidermis Epidermis-specific DNA methylation profiles in psoriasis and matched controls were measured using the Illumina Infinium HumanMethylation450 BeadChip platform (450K) (Illumina, San Diego, CA), which evaluates methylation status of 482,421 CpG sites covering key features of the human genome  (Bibikova et al. , 2011). The ChIP analysis methylation pipeline package was applied for data analysis  (Morris et al. , 2014). The beta-value was chosen as a measure of the methylation level, which ranges from 0 (no methylation) to 1 (complete methylation). On the basis of the methylation level of 470,903 sites, similar global methylation status was seen between psoriasis and controls, with a median beta-value of 0. 590 in controls and 0. 554 in psoriasis (PRE-UV).
Effect of phototherapy on psoriasis and DNA methylation Differential analysis using significance analysis of microarrays (SAM) was performed to identify significantly affected MVPs by phototherapy in paired samples. A methylation change with delta-beta40. 1 and FDRo0. 05 was considered significant. After 1 month of treatment (MID-UV vs. PRE-UV), the methylation level of 73 CpG sites was significantly modified. At the end of phototherapy (POST-UV vs. PRE-UV), a total of 2,108 CpG sites were significantly affected. Top 50 hyper and 50 hypomethylated MVPs are listed in Supplementary Table  S1  online, ordered by methylation changes following phototherapy (POST-UV vs. PRE-UV). DAVID (Database for Annotation, Visualization, and Integrated Discovery) functional annotation analysis was performed for 1,082 known genes that are proximal to the 2,108 MVPs.
450K data validation Validation of BeadChip measurements was carried out on selected CpG sites using OneStep qMethyl (Zymo Research, Irvine, CA). For all the genes tested, qMethyl data were highly correlated with array data, with Pearson's correlation coefficient (r) of 0. 96 for HN1L and IRF2, 0. 85 for IFI27, and 0. 90 for PDK2 (Po0. 001; Supplementary Figure  S1 online).
One patient (patient 5) left at the middle stage of phototherapy; thus, only PRE-UV and MID-UV samples could be collected. All patients had moderate-severe psoriasis and a history stating improvement by sun exposure. Clinical improvement was assessed by evaluation of erythema, desquamation, and induration following phototherapy. Three grade evaluation (excellent, good, and unsatisfactory) was performed due to clinical routine by an experienced nurse and included the patient´s statement of improvement. Clinical data on patients are shown in Supplementary Table  S6  online. Twelve healthy age-, sex-, and skin type-matched volunteers were also recruited, and two punch biopsies were taken from the buttocks.
Genome-scale DNA methylation array Bisulfite-converted DNA was used for methylation profiling using the HumanMethylation450 platform. iScan Reader was used to image BeadChips. The ChIP analysis methylation pipeline package was applied for data analysis  (Morris et al. , 2014). By default, ChIP analysis methylation pipeline filtered the data for detection P-valueo0. 01. Probes with o3 beads in at least 5% of samples per probe were filtered out and probes from X and Y chromosomes were removed, resulting in 470,903 probes. Intra-array data normalization using the BMIQ (Beta MIxture Quantile dilation) method  (Teschendorff et al. , 2013)  was performed for correcting bias introduced by the Infinium type 2 probe design. Singular value decomposition method  (Teschendorff et al. , 2011)  was used to assess the magnitude of batch effects in relation to biological variation.
The beta-value was chosen as a measure of the methylation level and was transformed to M-value for differential analysis  (Du et al. , 2010). The limma package implemented in ChIP analysis methylation pipeline was used to calculate the Benjamini and Hochberg FDR-adjusted P-value for differential methylation between psoriasis (PRE-UV) and controls. To identify significantly modified CpG sites following phototherapy, significance analysis of microarrays was performed in Mev 4. 8. 1 (Dana-Farber Cancer Institute, Boston, MA)  (Saeed et al. , 2003). Functional annotation analysis was performed using DAVID  (Huang da et al. , 2009a, b). Principle component analysis was performed using SIMCA software (v. 13, MKS Umetrics AB, Sweden).
Validation of 450K data Validation of BeadChip measurements was carried out using One- Step qMethyl (Zymo Research). The list of top differentially methylated CpG sites was analyzed, and primers for four CpG sites, cg27431500 (HN1L), cg20161089 (IFI27), cg11802666 (IRF2), and cg04091816 (PDK2), were designed (Supplementary Table  S7  online). Sufficient DNA was available from only four patients for validation. Methylation levels in four healthy controls were also determined. Real-time PCR was performed using 7900HT Fast Real-Time PCR system (Applied Biosystems, Foster City, CA).