dataesr/scientific-paragraphs-categorization huggingface dataset:
We used weighted additive mixed models to analyze temporal trends in median CD4 cell counts at the start of cART. The covariates sex and country income group, as well as their interaction, were included as fixed effects, country as a random intercept, and yearly trends smoothed by sex and country income group. Similarly, we analyzed the median CD4 cell count according to region instead of country income group. For this analysis, weights were normalized by region. We also modeled the proportion of patients starting cART with severe immunodeficiency (CD4 cell count <200/µL), using generalized additive mixed models, and we fitted this model to other CD4 cell count thresholds (<50/µL, <100/µL, <350/µL, and <500/µL). We used the data set that included imputed CD4 cell counts. In sensitivity analyses, we fitted models to the data set consisting of complete cases only.
Descriptive Analyses We received data from 1 472 098 patients. We excluded a total of 520 243 patients and 22 countries who did not meet the inclusion criteria. Supplementary Figure  S1  (see Supplementary Digital Content) shows the inclusion of patients. A total of 951 855 individuals from 55 countries  (16 LICs, 11  LMICs, 9 UMICs, and 19 HICs) were included (Table  1  and Figure  1 ). Five countries contributed 160-499 persons; 6 countries, 500-999; 20 countries, 1000-4999; 5 countries, 5000-9999; 12 countries, 10 000-24 999; and 7 countries, ≥25 000. The number of individuals included in each country ranged from 160 (Malaysia) to 350 595 (Zambia). The percentage of women was 57% overall and ranged from 5% in South Korea to 82% in the Democratic Republic of the Congo. In LICs, LMICs, and UMICs, the median (IQR) age of individuals starting cART was 35  (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42).
Our results are consistent with an earlier analysis of IeDEA and European data, based on individual patient data from 379 865 patients in 23 countries, which showed that CD4 cell counts in LICs and MICs increased from about 90/µL in 2002 to about 150/µL in 2009  [4]. Our results are also in line with analyses of individual patient data from a smaller number of countries  [5, 30, 31]. The weighting of estimates was another strength, with more weight given to the more precise estimates of median CD4 cell count, and by the number of patients starting cART in a given country and year  [18] , so that countries with many patients starting cART were adequately represented in our analysis. Our study also had several limitations. We included data up to 2015, but not all countries contributed data spanning the entire period from 2002 to 2015.
However, for the 5 Southern African countries, which provided information on clinical stage, the WHO stage distribution overall was similar in patients with reported and those with missing CD4 cell counts. These data indicate that, at least in Southern Africa, only a small portion of missing counts are due to poorer health. Data from some countries were limited to a small number of patients from a single clinic. We excluded these data sets because the data were probably unrepresentative of all patients receiving cART in those countries. Some data included in modeling of time trends may also not be representative of all patients receiving cART in the country. In particular, the clinics from LICs and MICs participating in IeDEA are mainly urban and capture data in electronic databases, indicating a higher level of resources.
Immunodeficiency at cART Initiation • CID 2018:66 (15 March) • 903  ViiV Healthcare ,  Merck ,  Janssen Cilag , and  Abbvie. B. C. has received grants and financial support from  Infectious Disease Institute  and the  NIH. G. C. has received grants and other support from  ANRS  and the  European Commission  ( FP7/2007-2013 ). I. J. C. has received grants from  NHS England. D. C. was a member of the HIV board of  Gilead  France until December 2015 and has received consultancy fees, grants, and other financial support from  Innavirvax ,  Janssen-Cilag ,  Merck Sharp & Dohme-Chibret, ViiV , and  Gilead. A. d. M. was a board member of  Gilead ,  Jansen ,  Merck Sharp & Dohme (MSD) , and  ViiV. S. D. W. has received consultancy fees, grants, or other financial support from  ViiV ,  MSD ,  Gilead ,  Janssen , and  BMS.
Phage Genome Annotation Putative coding DNA sequences (CDS) in the BONAISHI genome were predicted using Glimmer  (Delcher et al. , 1999)  and Genemark  (Besemer et al. , 2001). The coordinates of each translated open reading frames (ORF) were also inspected manually. ORF smaller than 200 base pairs (bp) were removed from the analysis. The predicted amino acid sequences were assigned manually by BLASTP and PSI-BLAST (cutoff e-value <10 -5 ) against the NCBI non-redundant database (January 2018) and InterProScan 5  (Jones et al. , 2014) , as well as the fully automated RAST server annotation service  (Aziz et al. , 2008). BLASTP was used to search for putative toxins in the databases MvirDB  (Zhou et al. , 2006) , VirulenceFinder  (Chen et al. , 2005) , Vibrio-base  (Choo et al. , 2014) , and t3DB  (Lim et al.
, 2009; Wishart et al. , 2015)  toxin databases. The IntegrallDB  (Moura et al. , 2009)  and ACLAME  (Leplae et al. , 2006)  databases were used to check for prophage-like sequences. tRNAScanSE  (Lowe and Eddy, 1997)  and Aragorn  (Laslett and Canback, 2004)  were used to check for tRNA. The genome map was produced using Artemis  (Rutherford et al. , 2000)  and DNA Plotter  (Carver et al. , 2009). The BONAISHI genome sequence has been submitted to the GenBank database under accession number MH595538.
General Features of BONAISHI Genome The genome of BONAISHI consists of a large doublestranded circularly permuted DNA sequence of 303,340 basepair (bp) with a % G+C content of 42. 5% (Figure  3 ). Terminal duplications at the extremities of the assembled sequence are 14,373 bp, giving a non-redundant genome of 288,967 bp. Glimmer and Genemark predicted 301 putative ORFs, which comprised 93. 8% of the total sequence and were mostly oriented in a single direction. Most ORFs initiate translation at an ATG start codon except for 6 ORFs, 4 of which have a GTG start codon and the other 2 a TTG start codon. We did not find any tRNA in the genome. Of the 301 predicted ORFs, 110 ORFs (36. 4%) had significant homologs in public databases and a biochemical function could be assigned for 62 of these (Table  2 , Figure  3 ).
Lysis, Host-Phage Interaction, and Lysogeny We were able to annotate two proteins (ORFs 23 and 138) involved into host-virus interactions. There were good blastp hits on proteins of unknown function in the NCBI nr database that could be expanded to known glycoside hydrolases (GH) in the expert database CAZY (Carbohydrate Active enZYmes db, http://www. cazy. org). These included a glycoside hydrolase with a conserved endopeptidase domain (ORF 23) affiliated to the GH23 family, which mostly include lysozymes. The protein encoded by ORF 138 belongs to the glycoside hydrolase family GH19, which comprises chitinases and lysozymes. Both enzyme groups catalyze the hydrolysis of polysaccharides containing N-Acetylglucosamine, but the gene sequence does not discriminate between the two. No genes implicated in lysogeny establishment or control (integrase/excisionase, transposases, ParA/ParB genes, attachment sites, transcription repressor, etc.
) were detected in the BONAISHI genome, even using prophage expert databases, which confirms that it is exclusively lytic. In addition, blastp searches using BONAISHI hosts genome did not find evidence of the presence of BONAISHI as prophage. Only three genes involved in DNA replication and recombination (ORF 225), nucleotide metabolism (ORF 192) and gene encoding for a phosphate starvation protein showed high score but the similarity was relatively low (<77%).
Metagenomic Analysis The global distribution of BONAISHI was investigated using marine viromes from various waters including coral mucus and the water from coral reefs (Table  S2 ). The highest number of FIGURE 3 | Genome map of BONAISHI. The 110 protein-coding genes are shown as colored blocks. Protein-coding genes that are transcribed in the forward and reverse direction are located on the external and internal circle, respectively. The functional assignments of the protein-coding genes are derived from blastp matches in NCBI nr and expert databases. We confidently discriminated proteins involved in general virion structure (light blue), head, and tail structure and assembly (dark blue), DNA replication,recombination and repair (red), nucleotide metabolism (orange), DNA transcription (pink), and host phage interactions (green).
Genes marked "h. p. " made strong matches to hypothetical protein sequences in the database with no identified functions (dark gray). The GC content of the genome sequence is indicated by the internal purple or green histograms. recruited reads was from the virome collected at ALOHA station in the North Pacific subtropical gyre (CAM_SMPL_00823): BONAISHI recruited 1. 04% of the reads with a mean identity of 58. 23%. None of the recruited reads exceeded 85% identity. We also used prokaryotic metagenomes to test whether the BONAISHI genome is found as a prophage in bacterial hosts. No bacterial reads were recruited.
In BONAISHI genome, we identified two glycoside hydrolases distantly related to known enzymes that belong to the families GH19 and GH23 using the expert database CAZY. Although the catalytic activities of these molecules cannot be determined based solely on the genome analysis, their overexpression and characterization might provide interesting tools for controlling V. coralliilyticus infection. A preliminary assay suggests that BONAISHI is a promising candidate for treating V. coralliilyticus infection. Studies investigating the action of V. coralliilyticus on coral symbionts showed that photosynthesis was inactivated by the expression of a Zn-metalloprotease  (Sussman et al. , 2009). Our experiments on Symbiodinum cultures infected by V. coralliilyticus showed that BONAISHI phage treatment was effective: adding the phage to the infected cultures rapidly reduced Symbiodinium PSII inactivation.
ACKNOWLEDGMENTS This work was supported jointly by the  EC2CO   PATRICIA  Project, the  TOTAL Foundation , and the  ANR CALYPSO  ( ANR-15-CE01-0009 ). We would like to thank  Andrew Millard  for discussion on phage transduction,  Simon Roux  for his help with metagenomic analysis,  Gurvan Michel  for his assistance with CAZYmes annotation,  Pei Ge  for her technical assistance, and  Tony Tebby  for the manuscript editing. We would also like thank the three reviewers for their constructive comments on a previous version of this manuscript. We are also very grateful to  Michel Galey ,  Alexandre Portier , and all the staff from  Whale Island Resort  for their hospitality and help during our stay.
IGH clonality higher than 2%. In parallel, MYD88 L265P and CXCR4 S338X mutations were screened by allele specific -polymerase chain reaction (AS-PCR), with a sensitivity of 0. 1%. 10, 11 he IGH gene was sequenced by HTS using a two-step PCR protocol adapted from Biomed-2 recommendations from 100 ng of genomic DNA. 12 Libraries were sequenced on an Illumina MiSeq platform and analysis were performed using Vidjil software. 13 A clonotype was defined as a dominant sequence showing a frequency of at least 1% of total reads, well separated from the polyclonal background reads. Patients' characteristics are reported in Table  1. In the anti-MAG group, all patients (N=26) presented an IgM monoclonal gammopathy, high anti-MAG antibodies titers, and clinical and electrophysiological evidence of demyelinating neuropathy.
Acknowledgments: the authors would like to thank the  Centre de Ressource Biologique-Santé of Rennes  ( BB-0033-00056 ) for providing biological samples. Correspondence: cedric. pastoret@chu-rennes. fr doi:10. 3324/haematol. 2017. 177444Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at www. haematologica. org.
DISCUSSION The present study focused on the TLR profile and function in two close splenic lymphomas entities: SMZL and SDRPL. To our knowledge and considering the rare incidence of the SDRPL, no data about TLR were nowadays reported in the literature and in particular no studies in both compartment in where tumoral SDRPL B cells can be detected. At the mRNA level and in splenic samples, we confirmed the higher expression of TLR9 in SMZL B cells compared to non-tumoral B cells, as previously reported  [12] , and described for the first time a TLR profile in SDRPL B cells. The TLR profiles were then analyzed by FCM on splenic and circulating B cells, showing the high expression of TLR7 and to a lesser extend the increased TLR9 in SDRPL. However, a few differences (in particular, lower TLR9 RFI than TLR7 RFI) were noted in comparison to previous profile reported by  Fonte et al.
Samples and cell purification This study was performed on frozen peripheral blood (PB) and spleen cell suspensions from patients with SMZL (PB n = 5, spleen n = 15) and SDRPL (PB n = 7, spleen n = 6) diagnosed according to the 2008 WHO recommendations  [22, 23]. The morphology, flow cytometry immunophenotyping, cytogenetics and molecular data were collected. Non-tumoral spleen samples (n = 7) and PB from healthy donors (n = 5) were used as controls. For functional analysis, the repartition of samples was as follows: non-tumoral (PB n = 5); SMZL (PB n = 5, spleen n = 2); SDRPL (PB n = 7, spleen n = 3, with 2 paired samples). Informed consent was obtained from all patients according to the Declaration of Helsinki. All B cells from splenic and PB samples were negatively sorted with CD2 and CD14 antibodies by using magnetic separation (Miltenyi Biotec).
TLR protein expression gated on CD19 + cells from splenic and PB samples was acquired on FACS Canto II cytometer and analyzed using DIVA software (BD Biosciences) as previously described  [14]. The expression of intracellular receptors: TLR3 (clone TLR3. 7), TLR7 (clone 66H3), TLR8 (clone 307D3. 01) and TLR9 (clone eB72-1665) were determined using the IntraPrep Permeabilization Reagent kit following manufacturer's recommendations (Beckman-Coulter). The surface receptors: TLR1 (clone GD2. F4), TLR2 (clone TL2. 1), TLR4 (clone HTA125), TLR5 (clone 19D759. 2), TLR6 (clone 86B1153. 2) and TLR10 (clone 3C10C5) were determined as previously described  [14]. The MyD88 expression (clone 603E10. 05) was performed with the PerFix-no centrifuge assay (Beckman-Coulter,) on NAVIOS cytometer using NAVIOS software (Beckman-Coulter) on CD19 + gated cells.
Cell culture and functional studies For all functional assays, B cells from PB were purified (>95%) as described above. For the proliferation assay, these purified B cells were loaded with 0. 25 µM of CFSE. TLR stimulation was performed with Imiquimod (IMQ) (Invivogen) for TLR7 or CpG: ODN 2006-G5 (CpG) (Invivogen) for TLR9 at final concentrations of 2. 5 and 5 µg/mL. Cells were cultured in RPMI1640 medium supplemented with 10% FBS, 2 mM L-glutamine, 100 U/mL Penicillin and 100 mg/mL Streptomycin. IL-6 production was measured with the DuoSet Human IL-6 kit (R&D Systems) from culture supernatants collected after 24 hours of culture in the presence or absence of IMQ or CpG. All cytometry analysis were performed on LSRII cytometer (BD Biosciences) and analyzed with FlowJo software (FlowJo LLC).
ADR Survey Among Individuals on ART for 48 to 60 Months (ART 48-60) For this survey, we selected ART clinics with more than 48 months activity to maximize the probability of obtaining the required sample size per clinic. A total of 10 clinics were eligible, all in urban regions. The required sample size (N = 400 participants, 40 per clinic) was calculated to obtain an estimate of drug resistance with a CI of ±5%, assuming a drug resistance prevalence of 18%, genotyping failure rate of 15%. ART 12-24 and ART 48-60 participants were consecutively recruited in selected study clinics if they were HIV-1 positive, aged ≥ 18 years, were still on ART, provided written informed consent and had been on ART for 12 to 24 months (ART 12-24 population) or for 48-60 months (ART 48-60 population). Socio-demographic and clinical data were collected using a questionnaire, which included participant age, gender, date of ART start, and ongoing ART regimen.
For the visualization of the lipid bodies, slides were prepared using the aqueous mounting medium Poly-Mount (Polysciences), observed via light microscope (Leica) and finally photographed using the Leica Application Suite software. Alternatively, after fixation, cells were labeled with 1 µg/ml of BODIPY 493/503 (Life technologies) for 15 min in order to visualize the lipid bodies by green fluorescence emission using a confocal microscope (Olympus BX51).
Phenotypic characterization by Flow cytometry Macrophages were centrifuged for 7 min at 1,200 rpm and then stained for 40 min at 4°C with fluorophore-conjugated antibodies FITC-anti-CD36 (clone 5-271), PerCP. Cy5. 5-anti-CD14 (clone HCD14), PE-anti-CD163 (clone GHI/61), FITC-anti-CD206 (clone C068C2) (Biolegend), FITC-anti-HLA-DR (clone G46-6), or PE-anti-CD274 (clone MIH1) (BD Biosciences), and in paral lel, with the corresponding isotype control antibody. After staining, the cells were washed with PBS 1×, centrifuged and analyzed by flow cytometry using FACSCalibur cytometer (BD Biosciences). The median fluorescence intensity were analyzed using FCS Express V3 software (De Novo Software, Los Angeles, CA, USA). The mean of the median fluorescence intensities (MFI) of the independent assays were used for comparisons between experimental conditions.
) was added 4 h prior the end of the coculture to block cytokine secretion. Thereafter, CFSE-labeled lymphocytes were first stained with anti-CD4-PerCP-Cy5. 5 mAbs (eBioscience), then fixed with 0. 5% PFA for 15 min. Second, cells were permeabilized with 500 µl Perm2 (Becton Dickinson, Cockysville, MD, USA) for 10 min and incubated with anti-IFN-γ-PE mAb (Invitrogen, CA, USA). Cells were gated according to its FSC and side scatter (SSC) properties analyzed on FACScan (Becton Dickinson). In order to gate out dead lymphocytes, the gate of CD4 T cells with increased SSC and low FSC was excluded  (25). Isotype matched controls were used to determine auto-fluorescence and non-specific staining. Analysis was performed using the FCS Express (De Novo Software) and results were expressed as percentages of IFN-γ pos /CFSE low / CD4 pos T cells induced by the different macrophage populations.
After extensive washing, blots were incubated with a HRP-conjugated goat anti-rabbit IgG Ab (1:5,000 dilution; Santa Cruz Biotechnology) or HRP-conjugated goat antimouse IgG Ab (1:2,000 dilution; Santa Cruz Biotechnology) for 1 h at room temperature. Immunoreactivity was detected using ECL Western Blotting Substrate (Pierce). Protein bands were visualized using Kodak Medical X-Ray General Purpose Film. For internal loading controls, membranes were stripped by incubating in buffer consisting of 1. 5% Glycine, 0. 1% SDS, 1% Tween-20, pH 2. 2 for 10 min twice, extensively washed and then reprobed with anti-β-actin (1:2,000 dilution; ThermoFisher, clone AC-15) or anti-STAT3 Ab (1:1,000 dilution; Cell Signaling Technology, clone D1A5). Results from Western blot were analyzed by densitometric analysis (Image J software).
statistical analysis All values are presented as mean and SEM of a number of independent experiments. Independent experiments are defined as those performed with macrophages derived from monocytes isolated independently from different donors. As most of our datasets did not pass the normality tests, non-parametric tests were applied. Comparisons between more than two paired data sets were made using the Friedman test followed by Dunn's Multiple Comparison Test. Comparisons between two paired experimental conditions were made using the two-tailed Wilcoxon Signed Rank. Correlation analyses were determined using the Spearman's rank test. For all statistical comparisons, a p value < 0. 05 was considered significant.
il-10 Deficiency Prevents the Foamy Phenotype in BMDM To confirm the role of IL-10 in the differentiation of FM, we evaluated whether BMDM derived from IL-10-knock out (KO) mice could indeed become FM after treatment with lipids from Mtb. First, we determined IL-10 production in M-CSF-derived BMDM from WT mice stimulated with mycobacterial lipids for 24 h. As shown in Figure  5A , unlike the undetectable level of TNF-α (data not shown), BMDM secreted IL-10 in response to mycobacterial lipid-stimulation. Second, we compared whether BMDM derived from WT or IL-10-KO mice differed in their propensity to accumulate lipid bodies in response to Mtb-derived lipids. As illustrated in Figures  5B, C , IL-10-deficiency prevented the foamy phenotype induced by Mtb lipids, which in turn could be partially reverted by the addition of exogenous IL-10.
acKnOWleDgMenTs The authors thank Federico Fuentes for his technical assistance. This work was supported by the Argentinean National Agency of Promotion of Science and Technology (PICT-2015-0055), the Argentinean National Council of Scientific and Technical Investigations (CONICET, PIP 112-2013-0100202), the Alberto J. Roemmers Fundation (2016), the bilateral cooperation programs ECOS-Sud (A14S01) and CONACYT/CONICET, the National Council for Science and Technology Mexico (CONA CyT FC 2015-1/115), the Centre National de la Recherche Scien tifique, the Agence Nationale de la Recherche (ANR 2010-01301, ANR14-CE11-0020-02, ANR16-CE13-0005-01, ANR-11-EQUIPEX-0003), the University of Toulouse, and the Fondation pour la Recherche Médicale (www. frm. org, grants DEQ20160334902 to ON and DEQ20160334894 to IM-P).
Clinical data were prospectively collected. Among 833 patients, 747 received a first transplant. Seventy-two patients (9. 6%) had never been dialyzed. 675 patients (81%) were included in this cohort. One hundred and thirty eight patients were on PD (20. 4%) and 537 on HD. Calcineurin inhibitors and Mycophenolate Mofetil were widely used as immunosuppressive regimen. Cytomegalovirus (CMV) prophylaxis was given according to each center practice. Almost all CMV-exposed patients received valganciclovir for 3 months. All CMV-naïve patients having received a CMV positive kidney received valganciclovir for 3 or 6 months. All patients received Pneumocystis antimicrobial prophylaxis with trimethoprim-sulfamethoxazole for at least 6 months.
Clinical parameters including: body mass index, diabetes mellitus (type 1 or 2), chronic heart failure diagnosed by a cardiologist, history of cardiovascular events (myocardial ischemia, stroke, peripheral arterial disease, and carotid endarterectomy), active tobacco defined by consumption of at least 1 cigarette per day, and statin treatment were recorded. Dialysis patients were included at least 6 months after the onset of renal replacement therapy. Dose and duration of dialysis were also recorded. All patients were previously informed and gave their consent. The study was approved by the ethic committee (Approval 13/686) and registered in clinicaltrials. gov (NCT02116270).
Cell debris and doublets were excluded on the basis of side versus forward scatter. Cells were analyzed on a FACS CANTO II cytometer (BD Biosciences) using FACS Diva (BD Biosciences) software. Recent thymic emigrants (RTE) were defined as CD45RA + CD31 + CD4 + T cells  [10]. Data were analyzed by considering the percentage of RTE among CD4 + T cells (RTE frequency or RTE%) and the absolute numbers of circulating RTE/mm 3. Naive CD4 + and CD8 + T cells was defined as CD45RA + CD28 + , and terminally differentiated CD4 + and CD8 + T cells was defined as CD57 + CD28 -. Pro-inflammatory monocytes were stained on fresh samples with the following conjugated antibodies directed against CD45 (APC, Pharmingen), CD14 (ECD, Immunotech), CD16 (PC-7, Immunotech), HLA-DR (FITC, Pharmingen), CD86 (PE, Immunotech) according to the manufacturer's recommendations.