dataesr/scientific-paragraphs-categorization huggingface dataset:
001 for both). There is a decrease between day 7 and convalescence, but it is not significant. In Thai, the DHF group has a significantly higher OSBPL10 expression compared with all other groups. Considering both datasets, it seems that OSBPL10 expression is very low in the acute phase, increases significantly at the end of the acute phase, and decreases again in convalescence. For both genes, results in Cuban patients showing warning signs were similar to the ones observed in the totality of patients. These results show that both gene expressions are altered along the dengue disease progression. We further checked which pathways could have both genes acting together (in Ingenuity database; https://targetexplorer. ingenuity. com/index. htm), and found that they play a central role in the LXR/RXR activation pathway, related to cholesterol metabolism and cytokine production in macrophages (Fig X and Table S in S1 Text).
GWAS genotyping and data quality control Genotyping was performed for the Illumina Human Omni 2Á5 chip and calls were obtained on the Illumina IScan Microarray System by using the Genome Studio software. Quality control was performed in PLINK  [47] , and SNPs with more than 5% missing genotypes, minor allele frequency (MAF) below 1%, and Hardy-Weinberg equilibrium deviation p-values of less than 0. 001 were filtered out. All samples were checked for missingness (threshold of 1Á93%), outliers in principal-component analysis (PCA), excess rate of heterozygous loci, and evidence of second-degree relatedness or higher (identity by descent >30%; or identity by state >90%). All studied samples passed these criteria. SNPs located in X and Y chromosomes and in mitochondrial DNA were removed, leading to a final account of 1,922,396 autosomal SNPs.
Global ancestry in Cuba and its influence in dengue infection outcome Cuban samples were merged with populations from Europe, Africa, Latin America and East Asia (Table A in S1 Text), so that the total final dataset contained 389,574 common SNPs. Ancestry components (K, from 2 to 10) were evaluated in all Cuban groups using the program ADMIXTURE  [48] , after pruning SNPs for pairwise linkage disequilibrium (r 2 > 0Á4 in 50-SNP windows), ending up with a total of 77,782 SNPs. The optimal K was estimated through cross-validation of the logistic regression. Two-tailed Wilcoxon rank-sum tests were applied to assess the significance between ancestry proportions in the Cuban groups.
Admixture mapping Local ancestry analysis was performed through RFMix algorithm  [49]. 50 Southern European (Italian) and 50 Yoruban samples from the 1000 Genomes database  [50]  represented the parental European and African components, respectively. These samples were phased together with the Cuban samples in SHAPEIT  [51]  with the fine scale HapMap phase II genetic map. A test in chromosome 22 was performed with the Spanish sample from 1000 Genomes database replacing the Italian to confirm that results were identical. The difference in the African proportion between asymptomatic/controls and cases was calculated for every position along each chromosome in the Cuban comparison groups (HCG, FCG and OCG), and genomic regions significantly enriched for the African ancestry in asymptomatic/controls were considered as being outside the range defined by the genome mean + 3SD.
mRNA expression in other datasets, potential functional role and positive selection Expression of significant genes and genotypes was checked also in public datasets: 1) 465 RNASeq performed in European and African lymphoblastoid cell lines by the 1000 Genomes project  [21] , expressed in reads per kilobase of exon per million reads mapped (RPKM) and extracted from ArrayExpress (E-GEUV-1); 2) Thai whole blood transcriptome (GDS5093)  [22]  from nine healthy controls, 28 samples collected between days 2 and 9 after onset of symptoms (acute illness) from secondarily infected patients (18 DF and 10 DHF), and 19 samples collected at convalescence, four weeks or later after discharge. GSEA software  [52]  was used for gene set enrichment analysis of the LXR/RXR activation pathway in the Thai dengue dataset  [22]  by considering three sets of genes: lipid metabolism, LXR/RXR activation and NF-kB activation.
Haplotter database (http://haplotter. uchicago. edu/) was used to explore recent positive selection through iHS measure (detects selective sweeps at 50-80% frequencies). By using the selscan package  [53] , another measure of positive selection (XP-EHH-detects selective sweeps above 80% frequency) was applied to the Cuban HCG. The significant SNPs were ascertained for location in regulatory regions by using EPDNew  [54]  and HaploReg  [55]  tools. EDPNew comprises organism-specific (we obviously used H. sapiens) transcription start site (TSS) collections automatically assembled from carefully selected mass sequences for genome annotation data. HaploReg annotates non-coding diversity by using LD information from the 1000 Genomes Project that allows one to visualize linked SNPs and small indels along with their predicted chromatin state, conservation across mammals and their effect on regulatory motifs.
This extended OSBPL10 segment (haplotype and immediate 5' region) has probably been under positive selection in the African Yoruban population, as inferred in the Haplotter tool based on HapMap dataset (iHS measure; Fig T in S1 Text). The positive selection of OSBPL10 gene was confirmed in Cuban HCG when applying XP-EHH measure (Fig M and Tables M-Nin S1 Text). Therefore, it seems that the OSBPL10 haplotype and its 5' region, although non-.
Acknowledgments We dedicate this paper to the memory of Professor Gustavo Kourı ´. We thank all the  Cuban individuals from Havana and Guantanamo cities  who agreed to participate in this study. The authors express thanks to  Dr Torreblanca  from the  Centre of Hygiene and Epidemiology of Guantanamo City , to  Dr. Raiza Martinez  from the  Salvador Allende Hospital , and to  Dr. Rosa Martinez  and technicians  Barbara Marrero  and  Jose Rodriguez  from the  Pedro Kourı ´Tropical Medicine Institute , for their support in the samples collection. The authors also thank the technician  Laure Leme  ´e, from the  Eukaryote Genotyping Platform Institut Pasteur , for her helpful support with the genotyping. Thanks also to  Dr. Daniel Limonta  for his helpful reviewing of this paper.
The research leading to these results has received funding from the  European Commission Seventh Framework Programme  [https://ec. europa. eu/research/fp7/index_en. cfm] for the  DENFREE  project under Grant Agreement no. 282378. PT had a PhD grant from the  People Programme  ( Marie Curie Actions ) of the European Union's  Seventh Framework Programme  (http://ec. europa. eu/research/mariecurieactions/)under  REA  grant agreement no. 290344  (EUROTAST) and MO a PhD grant from  FCT ,  The Portuguese Foundation for Science and Technology  (https://www. fct. pt/fct. phtml. en)with reference  SFRH/BD/95626/2013. I3S is financed by  FEDER  funds through  COMPETE 2020, Portugal 2020 , and by  Portuguese funds through FCT/Ministerio da Ciência, Tecnologia e Inovacão  ( POCI-01-0145-FEDER-007274 ).
RNA extraction from isolated colonocytes and microarray experiment After three washes in PBS by centrifugation (200 g, 3 min), isolated colonocytes were immediately homogenized in Trizol and stored at -80 °C prior total RNA extraction  [26]. A subsequent step of RNA purification was performed using the RNeasy Mini Kit and DNase I (Qiagen). RNA integrity was checked using a 2100 Bioanalyzer (Agilent Technologies). Sixteen colonocyte RNA samples (8 from NPD and 8 from HPD groups) were used for microarray experiment with SurePrint G3 Rat Gene Expression v2 8x60K Microarrays (AMADID: 028279) according to the manufacturer instructions (Agilent Technologies). Differential analysis of transcriptomic data was performed with the Bioconductor R package Limma  [27]. Data were normalized with a log2 transformation, centered by array and replicate spots were averaged.
Real-time PCR Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate microarray experiment using a set of rat-specific primers (Eurogentec) which were designed using the Oligo Explorer 1. 1. 0 software (Gene-Link), based on published sequences of the target genes (sequences available on request). After cDNA synthesis from mRNA using the High Capacity cDNA Reverse Transcription Kit (Life Technologies), qRT-PCR was performed using the power SYBR Green PCR master mix on a StepOne Real-Time PCR system platform (Life Technologies). Gene expression levels for each sample were normalized relative to the Hprt gene, using the 2 -ΔΔCt calculation.
Western blot Isolated rat colonocytes were lysed in RIPA buffer containing a protease inhibitors cocktail (Roche). ). Each 15 min, the tissues were successively voltage-clamped to zero to obtain the short-circuit current (I sc , μA/cm 2 ) and a ± 5 μA current was pulsed to measure the trans-mural electrical resistance (R t , ohm•cm 2 ). Analogue signals were digitized using the PowerLab® 8/35 data acquisition system and analyzed with the LabChart® software (AD Instruments). FITC dextran (FD4, Sigma) was used to evaluate the epithelial barrier integrity. After the 15 min tissue equilibration step, FD4 was added to the chamber mucosal side at the final concentration of 0. 2 mM. 100 μL aliquots were collected from the serosal side every 15 min over two h and replaced with 100 μL of fresh KRB.
A B Fig. 4  a NF-κB signaling canonical pathway diagram. This pathway was significantly enriched in the set of genes regulated by the high-protein diet (HPD). The diagram was obtained from Ingenuity Pathway Analysis software and depicts genes implicated in this pathway and their interactions. Expression of genes colored in green and red were respectively downregulated (q < 0. 1) and upregulated (q < 0. 1) in colonocytes of rats fed an HPD when compared to a normal-protein diet (NPD). The list of differentially expressed genes implicated in this pathway is presented in Additional file 6: Table  S3. b Relative expression values of a selection of significantly differentially expressed genes (q < 0. 01) participating to the NF-κB signaling pathway in the colonocytes of rats fed an HPD when compared to an NPD.
The expression values were obtained by microarray experiment and normalized to the mean value in the NPD group. Nfkbie (NF-κB inhibitor epsilon), Rela (RELA proto-oncogene, NF-κB subunit), Nfkb1 and 2 (NF-κB subunit 1 and 2), Traf2 and 6 (TNF receptor associated factor 2 and 6). Data presented on histograms are means +/-S. E. M Numerous genes downregulated in colonocytes by the HPD participate in cell metabolism and notably in protein synthesis. Interestingly, several bacterial metabolites derived from amino acids (p-cresol, hydrogen sulfide and ammonia) inhibit mitochondrial respiration when present in excess  [10, 13, 14]. In addition, HPD increased proton leaks in rat colonocyte mitochondria leading to a lower energetic efficiency  [10]. Therefore, it is tempting to propose that the downregulation of genes implicated in cell metabolism may represent an adaptation allowing ATP saving in colonocytes during HPD.
Tfrc (transferrin receptor), Mt1a, 2a, 3 and 4 (metallothionein 1A, 2A, 3 and 4), Ppp2r2a (protein phosphatase 2 regulatory subunit B alpha), Ndrg1 (N-myc downstream regulated 1), Prdx1 (peroxiredoxin 1). b Staining of Ki67 by immunohistochemistry on distal colon of rats fed an NPD or an HPD. Ki67 labelling index was calculated as the percentage of Ki67 positive cells relative to the total number of cells within the same crypts. c Proliferating cell nuclear antigen (PCNA) protein expression was quantified by western blot in colonocytes of rats fed an HPD or an NPD. Band intensity was quantified and normalized to the intensity of the band corresponding to actin. b-c Mean values were compared with a t test. a-c Data presented on histograms are means +/-S. E. M overexpression in colonocytes of markers of epithelial proliferation such as metallothioneins (up to 5.
Defb3, 4, 10, 15, 19, 22 and 30 (β-defensin  3, 4, 10, 15, 19, 22 and 30). c Claudin 1 protein expression was assessed by western blot in colonocytes of rats fed an HPD or an NPD. Band intensity was quantified and normalized to the intensity of the band corresponding to actin. e-f Barrier function was evaluated with Ussing-chambers in distal colon of rats fed an NPD or an HDP. e Transmural resistance was measured for 15 min after mucosa mounting in the chamber. f FITC-dextran (FD4) transport from mucosal to serosal side was recorded during two hours and FD4 apparent permeability (FD4 P app ) was calculated. c-e For each parameter, mean values were compared with a t test. b-e Data presented on histograms are means +/-S. E. M previous electronic microscopy observation showing that there was no alteration of tight junction structure in colonic epithelium of rats fed an HPD  [10]  and with another study showing that colonic barrier function is preserved in HPDfed piglets  [20].
, 2013; Lewis et al. , 2014)  or within the context of endurance events held at high altitudes  (Quindry et al. , 2008). However, given the numerous potential confounding factors inherent to field investigations, the present review was limited to the studies performed in a controlled and standardized manner. In particular, the Medline and Web of Science databases were utilized for the identification of pertinent papers using the following keywords: hypoxia or altitude, exercise or training, combined with oxidative stress and/or antioxidant capacity. The search yielded six eligible studies that also reported activity and nutritional-intake levels. These studies are summarized in Table  1. One of the first studies that investigated the effects of prolonged hypoxic exposure and concomitant daily exercise was performed at Pikes Peak high altitude research facility  (Subudhi et al.
Work in the unit is supported by grants from the  ANRS , the " CHIKV-Viro-Immuno "  ANR-14-CE14-0015-01  and " TIMTAMDEN "  ANR-14-CE14-0029  projects, the  Labex IBEID  program  ANR-10-IHUB-0002 , the  Vaccine Research Institute , and  Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Hence, quantification of adiposity by μCT was mostly compared to direct post-mortem weighing of abdominal and subcutaneous fat pads  [31, [33] [34] [35]  and more recently, to in vivo qNMR in mice  [30] ; body composition evaluated by BIS was correlated to values obtained by isotopic dilution and chemical carcass analysis  [38, 39, 42]. To our knowledge, there is however no report of a comparison between μCT and BIS in mice. Therefore, the present study was carried out to evaluate and compare the accuracy and the uncertainty of measurement of μCT and BIS in this species. For this purpose, the proportion of adipose tissue was measured with these two methods and by direct post-mortem tissue weigh, and correlations between the data were established. Intra-mouse variations were also calculated.
Materials and methods Animals A total of 51 male C57Bl/6J mice were housed in standard conditions (12 hours light/dark cycle, temperature controlled) and had ad libitum access to food and water. A first group of 5 mice was used to determine the density of visceral and subcutaneous adipose tissue (see below). A second group comprising 24 mice was defined, in which fat mass (FM) was evaluated by BIS, μCT and in some of them, adipose tissue weight (see below); data served for the evaluation of uncertainty of the BIS and μCT methods (Study 1, n = 3) and for the analysis of the correlations between the different methods of measurement of FM (Study 2, n = 21). A third group of 10 mice was used to evaluate the inherent error of the in vivo measurement (due to physiological movements) by the μCT (Study 3).
The length between "B" and "C" electrodes was measured; this length, together with age and body mass of the animal is used for the calculation of the different parameters given by the BIS device. Thirty continuous BIS measurement (1 measurement/s) were acquired from 4 kHz to 1MHz. The acquired data were downloaded and analyzed with the proprietary software (ImpediVet BISI version 1. 0. 0. 4) to determine TBW (L) and global FM (%). The whole procedure took less than 10 minutes.
Study 3: Comparison of ungated and gated scans There was no statistically significant difference between the proportions of adipose tissue in the thoracic region measured by μCT with or without respiratory-gating and before and after manual lungs area correction (see Table  2 ). Values ranged from 22. 95 ± 4. 01% to 25. 04 ± 3. 73%, with a maximal error of 2. 1± 0. 7%. Micro-CT scans were performed in 10 mice, with and without respiratory-gated conditions, on the same field of view (thoracic region). Scans were then analyzed with and without manual correction in lungs area. Data are presented as mean ± SD of the 10 mice. Statistical analysis was performed using a one-way ANOVA analysis.
In agreement, FM values varied considerably over 15 independent measurements (3x/day, 5 consecutive days), with a coefficient of variation of 17%. Our data show that the time of measurement represents the most important factor of variability (CV = 13. 6±7. 0% for data obtained at morning, noon and afternoon), most probably reflecting changes in the nutrition and hydration status of animal along the day. Thus, performing BIS evaluation always at the same time seems crucial to improve reliability. The influence of the time of measurements is much less pronounced for μCT. Based on our results we cannot reject the importance of measuring at the same time although for μCT. In the BIS procedure, accuracy in the determination of the distance between B and C electrodes also plays a key role. This length, together with age and body mass of the animal, is used for the calculation of the different parameters given by the device.
Patients and controls Plasma samples from 145 HIV-HCV co-infected patients undergoing regular follow-up at Nı ˆmes University Hospital between September 2012 and September 2014 were analyzed. Additionally, plasma from 100 healthy blood donors from Etablissement Francais du Sang were analyzed as a control group. Included patients had no infectious disease within the 15 days prior to and following the blood sample. Routine blood parameters were performed on these samples including liver function tests, CD4+T-cell count and HIV RNA viral loads (VL). Demographic, clinical and immunological data concerning HCV genotype and fibrosis assessment were collected from medical records.
Data acquisition and statistical analysis The clinical database of the institution was searched using the clinical software (CLOVIS, 4Dv13) and appropriate keywords. When information was missing from numerical records, the paper files were retrieved if available. For each case fulfilling the inclusion criteria, data were recorded using a form created with EpiData v3. 1 Software (Lauritsen J. M. , Bruus M. & Myatt M. , UK/ Denmark). Information regarding file number, age, sex, body weight, duration of clinical signs, and definitive diagnosis were collected. Complete data were then exported into an Excel 2010 spreadsheet (Microsoft Office 2010, Excel 2010) for further statistical evaluation. Percentages for each subpopulation were calculated with a 95% confidence interval, using the asymptotic/Wald method (for groups in which n x p > 5, where n is the number of individuals in the concerned subpopulation, and p the estimate prevalence rate), or the exact binomial/Clopper-Pearson method (for groups in which n x p < 5, EpiTools, AusVet Animal Health Services).
Patients and study design This prospective, investigator-blind, randomized, controlled, parallelgroup, multicentre, two-arm, non-inferiority study was conducted at six fertility clinics in Denmark (two sites), France (one site), Hungary (one site), Switzerland (one site) and UK (one site). The primary outcome was defined as the total number of oocytes retrieved. The trial was assessor blinded, and all investigators, central assessors, laboratory personnel and sponsor staff involved in analysing and interpreting data were kept blinded to the treatment allocation throughout the trial. Blinding was ensured by providing patients with sealed and anonymous boxes with the study drug and avoiding any contact between assessors and study drug. Drug dispensing and accountability was carried out by dedicated personnel, such as appointed pharmacists or study nurses.
Patients with infertility, planning to undergo IVF, with or without intracytoplasmic sperm injection, who achieved successful downregulation (defined as endometrial thickness <7 mm or serum oestradiol level ≤50 pg/ml) with a standard GnRH-agonist long protocol regimen were selected for possible study inclusion between March 2011 and April 2013. Pregnancy outcome data were collected in the subsequent 9 months, whereas frozen embryo transfer data were collected during the following 2 years. The eligibility criteria were female age between 18 and 39 years, body mass index (BMI) 30 kg/m 2 or less, less than three prior completed ART cycles, baseline (day 2-3) FSH less than 10 IU/L and oestradiol less than 80 pg/ml, and a normal uterine cavity as demonstrated on recent hysteroscopy, sonohysterogram or hysterosalpingogram.
Supernumerary embryos were cryopreserved by slow-freezing procedure in all centres but Basel where vitrification of oocytes in the pronucleate stage was performed, according to Swiss legislation. Two weeks after oocyte retrieval, serum HCG levels were measured, even if bleeding had occurred. In an attempt to obtain data that accurately reflect the actual incidence and severity of OHSS in an IVF protocol, and to insure that this information was captured at each centre under generally comparable conditions, OHSS was characterized for each patient at the time of embryo transfer (early onset) and at the time of serum pregnancy test (late onset) using a standard OHSS evaluation form based on updated Golan criteria  (Golan and Weissman, 2009). Ongoing pregnancy rate was defined as a pregnancy showing ultrasound embryonic heart activity at 10-11 weeks after embryo transfer.
P < 0. 05 was considered statistically significant. Incidence of adverse events was compared using Fisher's exact test for comparison of Meriofert versus Menopur. SAS software (SAS Institute Inc. , UK was used for all statistical calculations. The sample size was calculated taking into account previous published papers of studies conducted with the reference product  (Platteau et al. , 2008). The sample size was calculated using the Schuirmann's two onesided test, considering the total number of oocytes retrieved, according to non-inferiority experimental design criteria and choosing a twosided alpha (0. 05), a power of 80%, a clinically significant difference of 2. 1 (20% of 10. 5), a standard deviation of 5. 9. According to this calculation, a minimum of 250 patients were required to demonstrate non-inferioritym, i.
e. , 125 patients per group. Taking into consideration the randomization blocks and some possible drop outs, a total of 270 patients were enrolled. Eligible participants were randomized in blocks of four at each site using a randomization list that was generated with Statistical Analysis Software. Randomization numbers were assigned chronologically. The investigators were asked to keep a record of the names of the patients and their corresponding randomization numbers, thereby allowing easy identification of data in a patient's file if required. The randomization code for each patient was provided to the investigators in individual sealed envelopes for emergency use only, i. e. , in case of onset of a serious adverse event that required unblinding of the treatment.