dataesr/scientific-paragraphs-categorization huggingface dataset:
Future Perspectives Anacetrapib is a potent CETP inhibitor developed by Merck. In a first clinical trial, anacetrapib increased HDL-C by 138 % and reduced LDL-C by 40 % in patients with coronary artery disease or at high risk for coronary heart disease on statin therapy. This clinical trial with the acronym DEFINE (Determining the EFficacy and Tolerability of CETP Inhibition with Anacetrapib), demonstrated the safety of anacetrapib and absence of significant changes in blood pressure, aldosterone and electrolyte levels  (Cannon et al. 2010). Currently, a phase III clinical trial is ongoing, acronym REVEAL (Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification), which will determine whether lipid modification on anacetrapib therapy reduces the risk of coronary death, myocardial infarction (MI) or coronary revascularisation in patients with circulatory problems and low LDL-C on statin therapy (ClinicalTrials.
gov identifier: NCT01252953). The results of this trial are expected at the beginning of 2017. Evacetrapib, designed by Eli Lilly & Company, is the fourth member of the CETP inhibitor class that is tested in clinical trials. A phase II clinical trial evaluated the efficacy of evacetrapib as monotherapy or in combination with the most prescribed statins in patients with either hypercholesterolaemia or low HDL-C levels. As monotherapy, evacetrapib (30 mg, 100 mg or 500 mg/day) dosedependently reduced LDL-C from 14 to 36 % and increased HDL-C from 54 to 129 %. Although the decrease of LDL-C was higher in combination with statins (49 % vs. 24 %), the increase of HDL-C was not stronger when compared to evacetrapib monotherapy  (Nicholls et al. 2011). No adverse effects were observed in this trial, with no changes in blood pressure or aldosterone levels.
Thus evacetrapib appears to be well-tolerated  (Nicholls et al. 2011). The benefits of evacetrapib in combination with statins will be determined in a phase III randomised outcome trial, acronym ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High-Risk for Vascular Outcomes) (Estimated end date: January 2016; ClinicalTrials. gov identifier: NCT01687998).
ttpharma. com/ TherapeuticAreas/MetabolicDisorders/Dyslipidemia/HPP593/tabid/118/Default. aspx). The synthetic, non-thiazolidinedione PPARγ compound, INT131, improves glucose tolerance in rodent models of diabetes to a similar extent as rosiglitazone. However, no major adverse events, such as weight gain, haemodilution or plasma volume increase, were observed in INT131-treated rats compared to rosiglitazonetreated rats  (Motani et al. 2009 ). In a randomised, double-blind study, type 2 diabetes patients were treated 4 weeks with 1 or 10 mg of INT131. Consistent with the in vitro data, INT131 displayed a glucose-lowering activity and increased HDL-C levels without changing other lipid parameters  (Dunn et al. 2011 ). This molecule is currently tested in a comparative clinical study in type 2 diabetes patients treated for 24 weeks with INT131 or pioglitazone (ClinicalTrials.
gov Identifier: NCT00631007). In addition, a phase I clinical trial is ongoing to evaluate safety, tolerability and pharmacokinetic behaviour of a new PPAR α/γ modulator, DSP-8658, in type 2 diabetes mellitus and healthy subjects (ClinicalTrials. gov Identifier: NCT01042106). DSP-8658 is a non-thiazolidinedione compound which exhibits potent anti-hyperglycaemic effects, reduces plasma triglycerides and increases HDL-C levels with less side effects on, e. g. , body weight gain (press report: www. ds-pharma. com/ir/library/presentation/pdf). Finally, the new dual PPAR α/δ agonist GFT505, developed by Genfit, reduced plasma triglycerides and increased HDL-C levels in abdominally obese patients with either dyslipidaemia or prediabetes  (Cariou et al. 2011). A phase IIb clinical trial is ongoing to evaluate the efficacy of GFT505 in patients with non-alcoholic steatohepatitis (ClinicalTrials.
LXR-623 (WAY-252623) is a novel synthetic ligand with higher potency for LXRβ, which induces plaque regression in combination with statins in a rabbit model of atherosclerosis  (Giannarelli et al. 2012). LXR-623 entered in a phase I trial (NCT00366522) to test tolerance and safety in humans  (Katz et al. 2009 ). However, its development was interrupted because of adverse effects in the central nervous system with potential induction of psychiatric disorders.
Many of the genes in these GO classes overlapped and included nlp and cnc genes that are up-regulated by pathogen exposure and wounding. The 317 genes down-regulated following nhr-25(RNAi) were enriched for oxidoreductase activity, transporter activity, nutrient reservoir, and structural component/activity terms (Figure  S1 , Table  S4 ). Furthermore, when we performed GO analysis on the 138 genes up-regulated in both acs-3(ft5) mutants and nhr-25(RNAi) animals, we observed a similar enrichment in defense response, response to biotic stimulus, and cell killing genes, as well as an enrichment in molting/ cuticle genes (Figure  1B ). The genes populating these GO classes are highlighted in Tables S1-S4. To further investigate these biological themes, we performed Expression Analysis Systematic Explorer (EASE) analysis to compare our datasets to those in a database manually curated from the literature  [23, 24].
These differences may reflect the consequences of reducing nhr-25 transcript levels by RNAi versus defective NHR-25 DNA binding in the ku217 mutant. In support of this notion, NHR-25::GFP ChIP-seq data from L2 larvae generated by the model organism ENCyclopedia Of DNA Elements (modENCODE) project  [25, 26]  found NHR-25 enrichment near the nlp-31 and cnc-3 genes (http://modencode. oicr. on. ca/fgb2/gbrowse/worm/). Gene expression data from nhr-25(rf) animals matched with NHR-25 ChIP-seq from the same larval stage will be required to further explore whether NHR-25 directly regulates innate immunity genes. S1-4. (B-D) Analysis of enriched biological functions as determined by GORILLA-REVIGO analysis. Enriched biological processes in genes up-regulated in both acs-3(ft5) and nhr-25(RNAi) animals (B), in acs-3(ft5) mutants (C), and in nhr-25(RNAi) animals (D) using the GO visualization tool REVIGO  [22].
Using this tool, similar functional categories cluster together in two-dimensional space. REVIGO uses a simple clustering algorithm to represent GO data and represents the semantic similarity of the data on the x-and y-axes. Bubble color indicates p-value derived from the Gene Ontology enRIchment anaLysis and visualization tool (GORILLA), and bubble size is proportional to the frequency of GO terms in the Gene Ontology Annotation database. Colors corresponding to log10 p-value are provided in the legend. doi:10. 1371/journal. pone. 0092552. g001 We also tested the effect of simultaneously inactivating acs-3(ft5) and nhr-25(ku217) by examining pathogen responsive gene expression in an acs-3(ft5);nhr-25(ku217) double mutant. We observed similar expression of most assayed antimicrobial peptide genes in the double mutant compared to the two single mutants (Figure  2 ).
Similarly, nhr-25(RNAi) also caused strong expression of the nlp-29p::gfp reporter (Figure  S2 ). The microarray, qPCR, and nlp-29p::gfp reporter data indicated that acs-3(lf) and nhr-25(rf) lead to expression of immune genes during growth on a standard lab diet of E. coli OP50, with strong expression already apparent in L4 stage larvae. To determine when the nlp-29p::gfp reporter is expressed during development we used a COPAS biosorter, which can separate animals on the basis of both size and fluorescence. Using this approach, we examined acs-3(ft5) and nhr-25(ku217) mutants for elevated nlp-29p::gfp reporter expression during development. We grew mixed stage populations of animals and scored both animal size (measured by time of flight (TOF)) and intensity of the nlp-29p::gfp reporter. Developmental stage was inferred by TOF: L1 = ,200; L2-L3 = 200-400; L4s = 400-600; adults = 600-800.
Microarray analyses Processing of RNA for microarray analysis, hybridization to Washington University/Genome Sequencing Center C. elegans 23 K spotted oligo arrays, and post-hybridization analysis scanning using a GenePix 4000 B scanner (Axon Instruments, Union City, CA) were performed as described  [20]. Independent data sets were generated for WT vs acs-3(ft5) and control L4440(RNAi) vs nhr-25(RNAi). The following ''Targets. R'' contents were used: FileNameCy3Cy5 c. elegans_A1vsB1_103. gprvectornhr25 c. elegans_A2vsB2_107. gprvectornhr25 c. elegans_A3vsB3_111. gprvector c. elegans_C1vsD1_104. gprvectoracs3 c. elegans_C2vsD2_108. gprvectoracs3 c. elegans_C3vsD3_0102. gprvectoracs3 Arrays were normalized with the ''maNorm'' function from the ''marray'' package, which uses within-print-tip-group intensity dependent location normalization using the loess function (R ''stats'' package) and reports log-difference (M) and log-average (A) values.
Pair-wise significance testing (mutant/RNAi vs. wild-type/ vector) was performed using the Bioconductor package limma  [20]  and p-values were initially corrected for multiple testing using the false discovery rate (FDR) method of Benjamini and Hochberg  [60]. We defined differential expression as |log2(ratio)| $0. 848 with the FDR set to 5%, and p-value#0. 001. The microarray data have been deposited in the Gene Expression Omnibus database (http://www. ncbi. nlm. nih. gov/geo/; accession series GSE48605). Gene names of differentially regulated genes were generated using the WBcel235 release in ENSEMBL BioMart (http://www. ensembl. org/biomart/martview/). Venn Diagrams and the gene overlap between the acs-3 and nhr-25 datasets were generated using BioVenn (http://www. cmbi. ru. nl/cdd/biovenn/).
Gene Ontology (GO) analysis was performed on the genes regulated by both acs-3 and nhr-25 using GOrilla  [21]. The GO visualization tool REViGO was used to generate a scatterplot of the functional classification of genes co-regulated by acs-3 and nhr-25  [22]. GOrilla is a web interface gene ontology browser that exports data to REVIGO, another web based tool that summarizes ontology data and plots them onto 2D space based on semantic similarity measures  [21, 22]. For EASE analysis, the WormBase Converter tool (http://www. ciml. univ-mrs. fr/applications/WB_converter/) was used to convert the gene names from the WBcel235 release to WS230 release gene names  [24]. EASE was then performed as previously described  [23, 24]. qRT-PCR analysis cDNA was synthesized from 2 mg of total RNA in a 40 ml reaction using the iScript cDNA synthesis kit (Bio Rad).
Lifespan and survival experiments were analyzed using the OASIS online tool which generates Kaplan-Meier survival curves, and statistical data such as p-values from log-rank (Mantel-Cox)  [67]. All statistical analyses are presented in Table  S8. For D. coniospora spore adhesion assays, L4 stage larvae were incubated with either undiluted or 5-fold diluted spore solutions for two hours. Animals were then mounted on a 1% agarose pad and images taken using a Leica MZ16 F (zoom 16:1) stereomicroscope. Spore attachment was then quantified. Spore concentration is a relative amount not an absolute amount. All strains are exposed to the same spore concentration within an experiment, but the concentration will vary between experiments. Statistical analyses for the spore adhesion experiments are provided in Table  S9.
Acknowledgments We would like to thank  Jerome Belougne  for worm sorting, members of the  Yamamoto lab  for helpful discussions and technical advice,  Stefan Taubert ,  Aimee Kao ,  Gabriela Monsalve , and  Lindsey Pack  for advice and comments on the manuscript. We thank the  Fred Hutchinson Microarray Facility  for preparation, imaging, and analysis of microarray data. We appreciate the help of  Soledad De Guzman  for preparing plates. Some strains were provided by the  CGC , which is funded by  NIH Office of Research Infrastructure Programs  ( P40 OD010440 ).
JDW was supported by postdoctoral fellowships from the  Terry Fox Foundation  (award # 700046 ) and the  Canadian Institutes of Health Research  (award # 234765 ). Research support was from the  NIH  ( CA20535 ) and  NSF  ( MCB-1157767 ) to KRY, the  National Institute of Environmental Health Sciences  ( ES021412-01 ) and the  Program in Breakthrough Biomedical Research  to KA. JE is funded by institutional grants from  INSERM  and the  CNRS , and program grants from the  French ANR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2014 Quartier et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4. 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1. 0/) applies to the data made available in this article, unless otherwise stated.
The procedures were leading to broad-based improvements in community engagement  [21] , diagnostic pathology  [27] , and consistent use of protocol-based treatment for BL  [26]. In concluding remarks, Dr. Kinyera noted that basic laboratory upgrades implemented to facilitate research sample collection and long-term storage have enabled fieldwork to be conducted in the rural areas of northern Uganda. To date, 427 potential BL cases have been spotted and 220 of them have been enrolled into the study. During the same period, 1201 location-matched controls had been enrolled. Dr. Esther Kawira, EMBLEM Study Co-PI in Tanzania, reported that infrastructure improvements similar to those described in Uganda had also been implemented to support EMBLEM scientific research in rural Tanzania. These include high-speed internet to support communication, data faxing and access to the EMBLEM share portal for secure transfer of sensitive research data, study protocol archives; basic research equipment such as ultra-low freezers, QBC hematology analyzers, and bench-top centrifuges.
Opportunities for African scientists to publish On behalf of Dr. Franco Buonaguro, Editor-in-Chief of Infectious Agents and Cancer journal (http://www. infectagentscancer. com/), Dr. Mbulaiteye described the importance of scientific publication and encouraged African scientists to take advantage of open-access journals. He explained that Infectious Agents and Cancer journal has prioritized papers reporting data on infectious agents that cause or are linked to cancer. This focus is important for Africa where up to one-third of cancers are caused by infections  [45]. Moreover, the open access policy guarantees that published research can be accessed immediately via any internet connection. To increase access to authors from low and middle income countries (LMICs) and sharpen focus, the journal has added sections on Clinical Oncology  [46]  and Cancer Centers in Resource Limited Settings  [47].
Capacity building for cancer research in Africa Dr. Joe Harford of the NCI presented a talk entitled "Capacity Building in Africa" that outlined concrete ways the NCI is supporting cancer research and prevention in Africa  [48]. To overcome the hurdle of preliminary data from a grant provider's point of view, which is critical for funded grants, the NCI has funded through AORTIC "Beginning Investigator Grants for Catalytic (BIG CAT)" Research in 2010 to support young researchers in Africa to conduct studies that could lead to grant applications by African scientists  [26]. Dr. Harford noted that BIG CAT grants have no categorical exclusions on the type of cancer research performed (bench, clinical, or epidemiological), but the projects should have a short lifespan (two years) and should be preliminary in nature.
Data sources Data sources included published literature, clinical trials, official price/tariff lists, a Delphi panel study, and national population statistics. Characteristics of clinical events are not countryspecific. Hence, data on clinical probabilities were derived from the international literature  (Bouza et al. , 2008; Lowy et al. , 2010; Louie et al. , 2011). On the other hand, for costs and information on therapeutic choices, the general recommendation is that country-specific data sources should be used whenever possible  (Drummond and McGuire, 2001). Therefore, a country-specific literature search was performed to identify local costs from official price lists in England. Additional estimates came from a Delphi panel, which allowed expert opinions to be gained on treatment patterns and associated health care utilization in the absence of robust published data.
, 2010). The estimates by the Delphi panel are used for the base case. A sensitivity analysis for recurrences is based on a range from 8 to 50%. The Delphi panel estimated a 6. 14% mortality rate for CDAD, similar to the 6. 9% reported in a study from Quebec  (Miller et al. , 2002). C. difficile causes most of the severe cases of AAD, and therefore in our model, all mortality data were considered to relate to C. difficile only and not to other causes of AAD.
Typical in-plane resolution was 0. 490. 4 mm. Image segmentation and fat quantification were performed using an in-house method developed as a plugin of the software OsiriX3. 6. 1 (OsiriX Foundation, Geneva, Switzerland). The image processing strategy is illustrated in Figure  1. After manual definition of tricuspid and pulmonary planes, the RV endocardium was automatically segmented using region growing. The lowerdensity threshold applied for region growing was set 3 SD above mean myocardial density, as assessed by drawing a 3cm 2 region of interest in the interventricular septum at midventricular level. A 2-mm-thick RV free wall layer was then automatically derived from RV endocardial segmentation using a dilatation operator. Myocardial hypodensity was automatically segmented in the RV free wall by using histogram thresholding, the cut-off for fat being defined as pixel density<À10 HU.
The extent of fat was expressed in percent of RV free wall. Segmented images were used to generate 3-dimensional meshes compatible with 3D-EAM systems using the software MUSIC (Multimodality software for specific imaging in cardiology, Liryc Institute, University of Bordeaux, Inria Sophia-Antipolis, France). In addition to RV and fat, patient-specific models also integrated manual segmentations of coronary sinus in order to facilitate registration, and coronary arteries in order to guide potential epicardial ablation.
Ablation Results In total, 8 sustained VTs (induced or spontaneous) were hemodynamically stable and mapped. All critical sites were confirmed at the epicardium and labeled on the 3D-EAM. All but 1 of the critical sites were located within the RV fat: at the border of RV fat segmentation (within 20 mm from the edge) in 6 sites, and deep inside fat segmentation in 1 site. Registration of MDCT data allowed direct visualization of coronary arteries and helped avoid coronary damage during epicardial radiofrequency delivery. Of 13 patients undergoing epicardial mapping, 6 (46%) had epicardial basal inferolateral LAVA located close to the right coronary arteries (within 5 mm) (Figure  3 ). Endocardial ablation abolished epicardial LAVA completely in 2 cases, and partially in 9 cases. Two patients had LV involvement and low-voltage scar in the LV epicardium.
Materials and methods HIV Circulating recombinant form Primary HIV infection Molecular epidemiology MSM France S U M M A R Y Objectives: We aimed to seek HIV sequences highly similar to CRF56-cpx, a recently described newly circulating B/CRF02/G recombinant HIV, in our local clinical microbiology laboratory sequence database. Methods: A recently implemented tool that combines a databank of all HIV nucleotide sequences obtained at our clinical microbiology laboratory with a search tool that uses BLAST was used. A comparative and phylogenetic analysis of HIV protease and reverse transcriptase fragments was performed. Results: We identified two sequences that were clustered with CRF56-cpx with a bootstrap value of 99% in phylogenetic analyses; these were obtained from two patients diagnosed with HIV in 2009-2011.
HIV protease-reverse transcriptase sequences obtained from these two patients shared a mean identity of 98. 2 AE 0. 2% with previously described CRF56-cpx sequences. Both case patients diagnosed with HIV in our centre were highly sexually active men who have sex with men. Conclusions: Our findings highlight the continuous expansion of HIV diversity in France and indicate that real-time surveillance of HIV molecular epidemiology, including the comparison of sequences from laboratory, national, and international databases, might be helpful to identify the emergence, circulation, and transmission of viral strains. ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.
org/licenses/bync-nd/3. 0/). BLAST and allows the identification of the sequences from this database that are the most similar to sequences recently recovered in our laboratory or released in the NCBI GenBank sequence database (http://blast. ncbi. nlm. nih. gov/Blast. cgi?PROGRAM=blastn&PAGE_TY-PE=BlastSearch&LINK_LOC=blasthome). 9, 10  searched for HIV sequences highly similar to CRF56-cpx in our sequence database, which contains 14 766 HIV protease and 14 673 HIV reverse transcriptase (RT) sequences obtained from plasma samples collected between 1996 and 2014, as described previously. 9 These HIV sequences correspond to the entire encompassing the protease gene and the 723 first nucleotides of the reverse transcriptase gene. Sequences analysed were those recovered in the present study, their best BLAST hits in our laboratory,  10  the NCBI nucleotide sequence database (http://blast.
ncbi. nlm. nih. gov/Blast. cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome), and a set of HIV reference genomes from the Los Alamos HIV sequence database (http://www. hiv. lanl. gov/content/sequence/HIV/mainpage. html). The sequences described in the present study are highlighted in grey. Sequences corresponding to the best BLAST hits (BBH) for HIV CRF56_cpx and recovered in our laboratory and from the NCBI GenBank nucleotide sequence database are indicated in boldface (in addition, those obtained from our laboratory are underlined). Sequence alignment was performed by the MUSCLE program (http://www. drive5. com/muscle/) and the tree was built with MEGA5 software (http://www. megasoftware. net/) using the neighbour-joining method. Branches with bootstrap values >50%, obtained from 1000 resamplings of the data, are labelled on the tree.
Results and discussion We identified two sequences that were clustered with CRF56cpx in our laboratory database, obtained from two patients in 2012. In addition, in GenBank using BLAST, we detected the fourth CRF56_cpx sequence described by Leoz et al. from a patient diagnosed with chronic HIV infection in March 2011. 8 omparative and phylogenetic analyses of the HIV protease-RT, protease, and RT fragments obtained in our laboratory, from Leoz et al. ,  6, 8  and from GenBank, showed congruently that sequences obtained from the two patients whose cases are reported here were clustered with CRF56_cpx, with a bootstrap value of 99% (Figure  1 ; Supplementary Material, Figures  S1  and S2 ). HIV protease-RT fragments from these six patients shared a mean identity (AE standard deviation) of 98.