dataesr/scientific-paragraphs-categorization huggingface dataset:
mansoni and S. japonicum  [56, 57]. Among these were rad 17 (ovary, vitellarium), cyclin 1 (ovary), glypican (ovary), and dynactin (ovary, vitellarium) as representatives of genes with elevated transcript levels indicating their functional relevance within the gonads. Furthermore, an IPA analysis of the combined inhibitor treatment predicted that the c-myc protein might have been activated, since genes theoretically regulated by c-myc were differentially transcribed. Along the same line IPA predicted the protein p53 to be inhibited following Herb A treatment. Since cmyc is able to cause proliferation inhibition (mitoinhibition;  [58] ) its putative activation may have contributed to the previously observed reduction of mitotic activity following treatment with these inhibitors. Moreover, c-myc expression and p53 inactivation were described as two cell-cycle events regulated by Src during mitosis  [59].
RNA extraction and microarray experiments RNA from inhibitor-treated or from control females was isolated using Trizol reagent (Invitrogen). Subsequently, a DNAse digestion was done with the RNAeasy kit (Qiagen) according to the manufacturer's manual. The quality of the isolated RNA was determined using Bioanalyzer microfluidic electrophoresis (Agilent Technologies). For microarray experiments a S. mansoni custom-designed oligonucleotide platform (60-mers) was used, with approximately 44,000 probes representing nearly the complete S. mansoni transcriptome based on available cDNA sequence data from S. mansoni and S. japonicum. This platform was produced by Agilent Technologies (described in  [36] , and all associated information (probes, annotation) is available at Gene Expression Omnibus (GEO) under the accession number GPL8606.
The obtained raw data were extracted using Feature Extraction software (Agilent Technologies) and are available under GEO study number GSE39732. For subsequent analyses, a gene was considered as expressed only if its corresponding probe exhibited signals that were significantly higher than background (employing default parameters from the Feature Extraction software and recovering the column ''IsPosAndSig'' from the output). A probe had to fulfil the criterion to have detectable expression in at least 75% of all replicas in at least one of the two conditions (inhibitortreated or control). LOWESS algorithm was used for normalisation of the intensities  [82] , and the log 2 ratios between inhibitortreated and control groups were calculated. Subsequently, an adjustment of these filtered data was done using an updated genome annotation to eliminate redundancy of the probes per gene  [37].
Hierarchical clustering was done using Spotfire  [84]. Functional analyses were performed for differentially transcribed genes; Gene Ontology (GO) analyses  [85]  of all three inhibitor data sets were done with the software tool Ontologizer  [86] ; parent child union  [87]  was selected to identify categories containing enriched genes, and the p-value was adjusted according to Benjamini-Hochberg (BH) correction  [88]. Further functional analyses were performed by Ingenuity Pathway Analysis (IPA; http://www. ingenuity. com; [89] ), which represents a tool providing curated information from the literature for human, mouse and rat models about canonical pathways, regulated transcription factors and their targets, and possibly regulated molecular networks, including signal transduction cascades (of which some contribute to human cancer and other diseases).
To this end, all S. mansoni genes were annotated with the corresponding human homolog (determined according to a search with the following blast parameters: e-value,10 210 and at least 60% coverage); genes that fulfilled these criteria were annotated with the label ''to be used in IPA = YES'' in the updated annotation  [37] , and they were uploaded to IPA along with their corresponding microarray transcription measurements. These putative homologs represented the basis for the identification of pathways and networks enriched with proteins encoded by significantly differentially transcribed genes; default settings were used, except for presentation of networks (140 molecules per network, number of networks: 10) and for ''user dataset'' as reference set.
These quantifications were done for both inhibitor-and DMSO-treated samples. Fold changes are available in Supplementary Tables S2, S5, and S8. Subsequently, log 2 ratios (treated/control) were calculated according to a previous study providing a solid basis for comparison of microarray and qPCR data  [91]. The efficiency of each qPCR was determined to be between 90-100%. Finally, the validity of the obtained ratios of qPCRs and microarrays was determined by Spearman's rank correlation coefficient (r s ) as well as the correlation of the intersection of the microarray data following hTGFb and TRIKI-treatment  [92, 93].
1, Smp_076650. 2; forward 59-ACGTTGT-TACTTCTTCAGTACTCC-39; reverse 59-ACTTTGTAGG-TAGTAAGCGCAC-39). As positive control for similar amounts of cDNA of each organ-sample the S. mansoni heat shock protein 70 gene (SmHSP70 accession number L02415; forward 59-TGGTACTCCTCAGATTGAGGT-39; reverse 59-ACCTTCT-CCAACTCCTCCC-39) was used since as it was described to be expressed throughout diverse life stages and tissues, and it turned out to be a suitable control  [94; Hahnel et al. , submitted].
Flow cytometry and data analysis Data were acquired on a FACSCantoII (BD Biosciences) and analyzed using WinList 5. 0 software (Verity, ME). (D) Expression of the costimulatory molecules CD80 and CD86 on gut DC from inactive UC patients and healthy controls displayed as the mean ± SEM. The statistical significance of differences between groups was determined using unpaired t-test and p < 0. 05 was regarded as significant (*p < 0. 05).
Proteinase K (PK) Digestion and SDS-PAGE/ immunoblotting Methods were performed as previously described  [32]. Briefly, after bead removal, amplified products were incubated at 45uC with PK (200 mg/ml) for 60 min, before their denaturation at 100uC in SDS-PAGE sample buffer. Samples were run on 12% NUPAGE gels and electrotransferred onto PVDF membrane. Western blotting, using the SNAP system (Millipore, St-Quentinen-Yvelines, France), was performed with 3F4 or 6D11MAb as anti-PrP monoclonal antibodies (MAb) (Signet/Proteogenix, 67412 Illkirch, France) for human and sheep prion detection respectively, and an anti-mouse IgG peroxidase-linked secondary antibody for chemiluminescent reaction (ECL reagent, GE-Healthcare France). The capture yield was calculated as follows: the amount of PrP res captured by plasminogen-beads was compared to the total amount of PrP res present in the input after acquisition of the chemiluminescent western blotting signals with the GeneGnome digital imager and quantification with the GeneTools software (Syngene, Frederick, Maryland, USA).
Acknowledgments We wish to thank  Prof. Claudio Soto  ( University of Texas Medical School Houston, Texas, USA ) for hosting us in his laboratory and for his advice at the very beginning of PMCA. We also wish to thank  Phil Minor  ( South Mimms, UK ),  Armand Perret-Liaudet  ( CHU-Lyon France ) and  Olivier Andreoletti (ENVT, Toulouse, France)  for providing us with informative samples.
Ethical considerations Ethical approval for the study was obtained from the Ethics Review Board, University of Nigeria. Each respondent gave a signed informed consent. In addition, the heads of each facility gave an informed consent before data was abstracted from each of them. Consent was obtained from the hospital authorities to use anonymized data extracted from the hospital database for the study. The IRB approved the study based on written consent obtained from the hospital authorities and based on the anonymous nature of the data abstraction. Some patients that were interviewed during the study also had information obtained from their medical records and these respondents gave their consent both for the interviews and the data abstraction. About a quarter of the patients who were interviewed also had data abstracted from their records.
Study Design, Sampling, Data collection and Analysis The study was a cross-sectional study comprising both household and hospital based surveys. The household survey involved households with children less than five years residing in the communities while hospital based survey involved patient exit interviews, retrospective and prospective data abstraction from case records. A pre-tested questionnaire was used to elicit information from patients leaving the health facilities after consultation and treatment for malaria. A list of all the households with children under five years in the two selected communities was compiled, so as to get a sampling frame. Systematic random sampling was used to select 500 households for the study. The primary caregivers or any other household representatives in each of these households were interviewed.
Six health facilities (1 secondary public hospital, 4 primary healthcare centres and a mission hospital) were purposively selected based on their geographic region and patient load. A total of 125 exit interviews were administered to caregivers of children that had been diagnosed with malaria after consultation and treatment. A proportionate sampling technique was used to assign the number of exit interviews carried out in the respective health facilities. This was complemented with retrospective and prospective data abstraction from 125 in-patient and out-patient case records. In the household survey, information was collected on the demographic characteristics of the respondents in each selected household, the malaria status of children under the age of five years, cost of treating malaria episode, household assets and monthly food expenditure.
Data on transportation costs to and from the facility where treatment was sought and any other costs incurred in the course of seeking treatment for malaria was also collected. At the facilities, consent was obtained from the hospital authorities to use anonymized data extracted from the hospital database for the study. The IRB approved the study based on written consent obtained from the hospital authorities and based on the anonymous nature of the data abstraction. Some patients that were interviewed during the study also had information obtained from their medical records and these respondents gave their consent both for the interviews and the data abstraction. About a quarter of the patients who were interviewed also had data abstracted from their records. Similar information as in the household survey was also collected from exit interviews and in addition any costs incurred in treatment of malaria before attending the facility.
In-patient data on costs of malaria treatment (drugs, laboratory tests, etc. ) were abstracted from case records within a year (11 months retrospective and 1 month prospective). Information on costs to the health care system-drugs, investigations, facility running costs (recurrent and non-recurrent) was abstracted from the accounts records and these were validated by both the head of accounts department and the facility head. The capital cost of the buildings were estimated by an estate valuer and a health economist. Depreciation rates were applied to both buildings and vehicles. Estimation of vehicles and laboratory equipment were not applicable to the health centre facilities as they run only outpatient services. N. B. Questionnaires will be made available to readers on request.
Data Analysis Data analysis was undertaken and frequency distributions analyzed. Summary statistics at both the household and provider levels were computed. For continuous variables, the mean and standard deviation were calculated while numbers and percentage were determined for categorical variables. The direct medical costs that were computed consist of drugs cost, diagnostics, administration fees and other costs incurred as a result of the treatment of malaria. The direct non-medical cost consisted of transport fare only. The household's indirect cost of treatment was the cost attributed to time lost when taking care of a sick child. Principal component analysis (PCA) was conducted to generate a socioeconomic status (SES) index and wealth quintiles based on per capita food expenditure and household asset ownership.
Linear programming models also sought to determine the amounts of sodium and potassium that both would be consistent with the ratio of Na to K of 0. 49 and would cause the least deviation from the existing food habits. The 6 sets of food patterns were created before and after an across-the-board 10% reduction in sodium content of all foods in the Food and Nutrition Database for Dietary Studies. Modeling analyses showed that the 2010 Dietary Guidelines for sodium were incompatible with potassium guidelines and with nutritionally adequate diets, even after reducing the sodium content of all US foods by 10%. Feasibility studies should precede or accompany the issuing of dietary guidelines to the public.
Dietary data Observed diets for 6 groups by sex and age were based on the 2001-2002 NHANES sample of 4295 individuals. Pregnant women and persons with reported daily intakes of less than 600 kcal/d were excluded  [15]. Nutritionally adequate food patterns were developed for men and women in 3 age groups, as follows: 20 to 30, 31 to 50, and more than 50 years. A modeled food pattern was created using LP models for each sex-age group. An LP model is defined by a list of food variables, a list of constraints (nutritional and behavioral constraints), and an objective function. In this study, the list of food variables was provided by dietary intake data from NHANES. Nutritional composition data were provided by the Food and Nutrition Database for Dietary Studies (FNDDS 1. 0) from the US Department of Agriculture (USDA).
Food variables Only foods that were consumed by participants in the 2001-2002 NHANES were entered into food groupings. Baby foods, alcohol, medical foods and supplements, electrolyte solutions, chewing gum, and foods with an energy density less than 10 kcal/100 g (eg, water, coffee, tea) were excluded. For modeling purposes, individual foods consumed by each age-sex group were collapsed into food categories that represented the food variables in each LP model. The number of food categories (ie, food variables) by age-sex subgroups varied from 85 to 128. The nutrient profile of each food category was calculated based on a weighted average of the nutrient contribution of each food  [16, 17] , as based on the FNDDS 1. 0 nutrient composition data  [18]  and frequency of occurrence in the 2001-2002 NHANES  [12, 13, 19, 20].
The impact of reducing sodium content of the food supply by 10% The food patterns for 6 age-sex groups were recalculated after the sodium content of all foods in the FNDDS database was reduced across-the-board by 10%. The feasibility areas reflecting this change are plotted in Fig. 2  as the combined shaded and unshaded hatched areas. This analysis showed that an across-the-board 10% reduction in the sodium content of the food supply had a minimal impact on the low energy food patterns. The feasibility of reaching the sodium goals by women was not affected. Fig. 2  -All combinations of potassium and sodium that are compatible with the fulfillment of a whole set of nutrient recommendations using the actual US food supply and assuming a 10% sodium reduction across the board for 6 sex-age groups.
This study had limitations. First, because the FNDDS 1. 0 database lacked vitamin D, the optimized food patterns did not include the vitamin D recommendation. Achieving the adequate intake for vitamin D (ie, 5 μg/d) in the optimized food patterns will likely require more milk and more fish than estimated by the present model. Because milk also contains sodium, the minimum amount of sodium may be underestimated. Second, the feasibility area for the permitted amounts of sodium and potassium in the optimized food patterns was a function of the LP model and its constraints. One such constraint was that the LP model was based on composite food categories and not on individual foods. A larger variety of individual foods may have allowed for larger feasibility areas and more combinations of individual foods that were compatible with the sodium and potassium goals.
However, the permitted amounts of potassium and sodium were more strongly influenced by the nutrient and consumption constraints than by the number of food categories, which ranged from 62 to 120. The number was adequate, given that a typical person consumes approximately 40 different foods per week  [14]. The nutrient composition of food categories as consumed was much more realistic than that of the idealized MyPyramid food groups  [32]. Another limitation related to food pattern modeling is that LP models lead to one unique solution for each sex-age group. There is no variability in the output result. By contrast, applying the LP model to individual diets allows the calculation of statistical distribution and provides more statistical power. However, previous studies in individual level LP modeling were based on 7-day food records from the nationally representative French enquete Individuelle Nationale des Consommations Alimentaires study, whereas the present NHANES database contained 1 day only.
Acknowledgment The authors were supported by  National Institutes of Health  grants  R01 DK 077068  and  R21 DK085406  (MM and AD) and by an unrestricted research grant from the  International Life Sciences Institute (ILSI) North America (PM). The funders were not involved in the study design; collection, analysis, and interpretation of data; writing of the paper; and/or decision to submit for publication. MM and PM have no competing interest. Adam Drewnowski  is a trustee of  ILSI  and a board member of the  ILSI Research Foundation.
1 empty vector (100 ± 8 versus 130 ± 11 nmol glutathione/mg protein). Interestingly, in drug-selected MCF7 cancer cells, which also overexpress ABCG2, the intracellular glutathione content was significantly higher than in the parental MCF7 cells (154 ± 7 versus 125 ± 10 nmol glutathione/mg protein). These data may indicate a long-term modulation of glutathione levels in various ABCG2overexpressing cell types. Since total glutathione is known to be essentially constituted of free GSH and low amounts of oxidized GSSG, we measured both components separately in the different cell lines, upon incubation with 2-vinylpiridine behaving as a thiol scavenger. In all cases, the remaining oxidized GSSG was too low to be detected (not shown here), indicating no evidence of any change in the ratio between reduced and oxidized forms of glutathione.
INABILITY OF ABCG2 TO CATALYZE AN ACTIVE TRANSPORT OF GSH Finally, we measured the direct transport of 3 H-GSH into ABCG2containing membrane vesicles. We found that, in contrast to ABCC1 serving as a positive control, no direct, ATP-dependent and specific inhibitor-sensitive, transport of tritiated GSH by ABCG2 could be detected in insect-cell membrane vesicles (Figure  7 ). Any ABCG2-mediated GSH transport could not be either determined at other 3 H-GSH concentrations (0. 1 or 1 mM, data not shown).
ACKNOWLEDGMENTS  Drs. S. E. Bates  and  R. W. Robey  from the  NCI at Bethesda, MD , are acknowledged for providing the different cell lines, and  Drs. H. Baubichon-Cortay  and  D. Lorendeau  for critical discussion about ABCC1-related CS. Charlotte Gauthier  was recipient of a doctoral fellowship from the  Ligue Nationale Contre le Cancer. Financial support was provided by the  CNRS  and  Université Lyon 1  ( UMR 5086 ), the  Ligue Nationale Contre le Cancer  (Equipe labellisée Ligue 2013), the  Région Rhône-Alpes  ( CIBLE 2010 ), the  Hungarian OTKA  ( 83533 ),  ERC Stg 260572 , and an international grant from  French ANR and Hungarian NIH  ( 2010-INT-1101-01 ;  NIH-ANR 10-1-2011-0401 ). Gergely Szakacs was supported by a  Momentum Grant  of the  Hungarian Academy of Sciences.
Patients undergoing RDN We carried out systematic reviews of the literature published elsewhere,  6, 7  and identified ENCOReD centers engaging in RDN. Patients being followed up in the framework of still ongoing investigator-initiated or industry-sponsored trials or observational studies awaiting independent publication could not be included. Following the 4th ENCOReD network meeting, held in Leuven on 26 April 2013, 10 centers with patients available according to the foregoing criterion volunteered to contribute data to this patient-level meta-analysis. Participating centers provided information on 166 consecutively enrolled patients who underwent RDN because of resistant hypertension. Of those, we excluded 57 because they did not have their ambulatory BP measured either at baseline or at 6 months of follow-up.
Statistical methods We used SAS, version 9. 3, for database management and statistical analysis. We applied t-tests to compare unadjusted means and to determine the significance of unadjusted within-group BP changes (follow-up measurement subtracted from baseline) and the w 2 -statistic to compare proportions. To compute significance of BP changes, while adjusting for baseline and accounting for center or study as a random effect, we applied a generalization of the standard linear model, as implemented in the PROC MIXED procedure of SAS package. In multivariable-adjusted analyses, we considered sex, age, body mass index, serum creatinine and a history of diabetes mellitus or cardiovascular disease as potential predictors of the BP responses. We also applied multivariable-adjusted logistic regression to identify predictors of BP status at 6 months of follow-up.
In the SYMPLICITY HTN-2 study, 3 the 24-h systolic BP decreased by 11 ± 15 mm Hg (P ¼ 0. 006) in 20 RDN patients and did not change in 25 controls ( À 3 ± 19 mm Hg; P ¼ 0. 51), resulting in a unreported nonsignificant between-group difference of 8 mm Hg, as recalculated from the published data (t ¼ 1. 61; P ¼ 0. 11). Remarkably, the SYMPLICITY HTN-2 report also did not include the baseline ambulatory BP in Table  1. 3  Our current study reports on the largest database of ambulatory BP measurements following RDN. Our results revealed smaller reductions in the office and ambulatory BP than those observed in the SYMPLICITY HTN-2 trial  3  or in a subsequent meta-analysis,  20  even though compared with these other studies  3, 20  our patients had similar office BP, treatment score, renal function and baseline characteristics, being mainly white and obese.
While the SYMPLICITY HTN-3 randomized controlled trial (NCT01418261)  37  is expected to be completed within the next few months, it is not sure that its results can be readily extrapolated to European countries. Despite the superiority of ambulatory over office BP to predict prognosis,  [31] [32] [33] [34]  particularly in the context of resistant hypertension,  32  the primary endpoint of this trial 37 is still the baseline-adjusted between-group difference in office systolic BP. Several smaller European trials ongoing in France (NCT01570777, NCT01588795) and Norway (NCT01673516) will also report by the end of this year or next year. These studies and others being planned include ancillary studies on cardiac and arterial structure and function that will achieve a high degree of standardization within the networked ENCOReD centers.
ACKNOWLEDGEMENTS The  European Union  (grants  IC15-CT98-0329-EPOGH, LSHM-CT-2006-037093-InGenious HyperCare, HEALTH-2007-2. 1. 1-2-HyperGenes , HEALTH-2011. 2. 4. 2-2-EU-MAS-CARA,HEALTH-F7-305507 HOMAGE  and the  European Research Council Advanced Researcher  Grant -2011-294713-EPLORE ) and the  Ministry of the Flemish Community, Brussels, Belgium  (grants  G. 0734. 09, G. 0881. 13  and  G. 088013N ) supported the  Studies Coordinating Centre, Leuven, Belgium. None of the authors received financial support for the current analysis.