dataesr/scientific-paragraphs-categorization huggingface dataset:
Discussion This study of the provision of the TABADO smoking cessation program to trainees in VTCs found a higher smoking cessation rate at 12 months in the intervention group. After adjustment, an odds ratio of 1. 8 indicated that smoking cessation occurred almost twice as often in the intervention group than in the control group (p=0. 03). Among intervention group, smoking cessation rate do not differ between EP and non-EP smokers. Interestingly, the difference in abstinence rates observed between groups is mainly due to other students rather than to the EP participants. This may illustrate the importance of the "group effect" on smoking behaviour and on motivation to quit smoking. Christakis emphasized that the decision to quit smoking is not taken by an individual in isolation but rather reflects choices made by groups of individuals interrelated directly and indirectly  [16].
Thus, an increase in the prevalence of a given behavior at the peer level may lead to an increased probability of such behavior at the individual level. We could cite as an example Powell's study  [22]  showing that moving a student from a school where no one smoked to a school where a quarter of the students were smokers increased the student's likelihood of smoking by about 14. 5 percentage points. In this TABADO study, the significant results of the effect of the number of EP participants in a classroom on the abstinence rate for non-EP participants is a strong argument in favour of our hypothesis and underscores the importance of offering a program and of assessing it on a collective rather than individual basis. The absence of any difference in abstinence between EP participants and other smokers may be due to the EP participants' higher dependence levels at baseline.
Primary outcome Most adolescent smokers who try to quit relapse within a year  [27]. Hence, a 12-month follow-up is appropriate to evaluate the efficacy of the TABADO program  [28]. Smoking status was evaluated by self-administered questionnaires and therefore was a self-reported statement of smoking. However, smoking status was confirmed in 140 randomly selected students by an exhaled carbon monoxide test. The questionnaire's sensitivity was 98. 5%, which demonstrated that smokers responded honestly to the question concerning their smoking status.
Acknowledgements The study was supported by the following institutions:  MILDT/INCa/Inserm  (Grant  2006 ),  Société de pneumologie de langue française  (PhD fellowship 2007), Ligue nationale contre le cancer (Grant  2008 ) and the  Conseil régional de Lorraine  (PhD fellowship 2008 and 2009). We thank the adolescents who participated in this research and vocational training centres professionals of  Arches, Epinal, Laxou, Metz, Montigny-les -Metz, Pont-à-Mousson, Roville-aux-Chênes and Thionville. We gratefully acknowledge  Catherine Thevenin , tobacco addiction specialist, for her participation in consultations;  Monique Guillaso ,  Catherine Litscher ,  Marie-Rita Monzel  and  Céline Simon  for their contribution to data collection;  Nicole Fischer  and  Nicole Koebel  for data entry;  Marie-Line Erpelding ,  Marc Soudant  and  Jean-Marc Virion , for data management and statistical assistance.
We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0. 61 (0. 44-0. 86). The corresponding HR OS was 0. 62 (0. 54-0. 71). HR CSS for prediagnosis PA was 0. 75 (0. 62-0. 91). The corresponding HR OS was 0. 74 (0. 62-0. 89). Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk).
Study Selection. We performed our MA according to a predefined written protocol. To be eligible, studies had to deal with the influence of pre-or postdiagnosis levels of PA (assessed using metabolic equivalent tasks (MET)) on CSS and OS among invasive nonmetastatic CRC patients. Across the various studies assessed, high PA levels usually corresponded to more than 17 MET hour/week. Publications were identified by an electronic search using online PubMed, updated on February 18th, 2013, with the following keywords employed simultaneously: "colorectal cancer, physical activity, and survival. " An EMBASE query was also performed, which did not bring any additional original reference. We also searched for a systematic review on this topic in the Cochrane Database of Systematic Reviews but did not find such publication.
Statistical Analysis. All selected studies directly provided hazard ratios (HRs) with their 95% confidence interval (CI). Thus, in none study, we had to calculate HRs from the numbers of events (cancer-specific deaths, overall mortality). We chose to pool adjusted HRs, since the variables of adjustment were almost identical for all studies (age, gender, BMI, tobacco use, alcohol, and red meat consumptions) and also since, rather curiously, adjusted HR values were more conservative than raw HRs. By convention, when higher PA levels were associated with improved survival compared with lower PA levels, HRs for detrimental events were set to be inferior to 1. We used EasyMA. Net software (http://www. spc. univ-lyon1. fr/easyma. net/), available online (Department of Clinical Pharmacology, Cardiology Hospital, Lyon, France); PN performed the statistical analysis.
Acknowledgment Thierry Bouillet is on behalf of Sport and  Cancer CAMI. Sport  and  Cancer CAMI  was founded in 1998. It was the first National Federation to develop and organise physical activity and sport practise for patients with any type of cancer, at any time of medical care, even when metastases or side effects are present. Sport and Cancer CAMI is present in about forty centres in France, inside or outside hospitals, and manages.
3A  and B ). Of note, neutrophil, monocyte and eosinophil counts were affected neither by IM alone nor by the combinatorial regimen (Fig. 3C  and data not shown). Among patients on IL-2 dose level III that experienced limiting toxicities (patient #10, exhibiting a grade 3 systemic capillary leak syndrome and patient #11, exhibiting grade 3 asthenia and anorexia), only patient #10 was monitored for the pharmacokinetics of IM and IL-2. This patient had the highest AUC (0-24 h) for IM and CGP74588 (106. 5 and 25. 1 μg. h/mL, respectively). 2] [33]  Moreover, a preclinical study has shown that IM may synergize with IL-2 at reducing lung metastases after an i. v. injection of B16F10 melanoma cells, which are not sensitive to the direct cytotoxic effects of IM. 34  Such a synergistic antitumor effect was mainly due to an increased cytotoxicity of TNF-related apoptosis-inducing ligand (TRAIL)-dependent HLA-DR + CD11c + B220 + NK1.
Patients and Methods Patient eligibility. Adult patients with metastatic or locally advanced solid malignancy, measurable or evaluable disease who were refractory to standard therapy were eligible for the study (Phase I IMAIL-2 trial approved by the Kremlin Bicêtre Hospital Ethics Committee [no 07-019] and the Agence Française de Sécurité Sanitaire des Produits de Santé [no A70385-27; EudraCT N°:2007-001699- 35 in 2007]. Further requirements included: chronological age > 18 y and physiological age < 70 y; more than four weeks since the last disease-specific treatment, adequate bone marrow function defined as an absolute white blood count ≥ 4 × 10 9 /L, neutrophil count ≥ 1. 5 × 10 9 /L, platelets ≥ 100 × 10 9 /L and hemoglobin ≥ 9 g/dL; SGOT, SGPT and alkaline phosphatases ≤ 2-fold the upper limit of normal (ULN) (≤ 3 ULN in case of liver metastases); bilirubin < 1.
Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. of inacceptable toxicity, disease progression or patient refusal to continue the study. Data from patients who withdrew prematurely from the study were not included in the final analyses. Chemicals. IM, [d8]-imatinib and N-desmethyl-imatinib (CGP74588) were kindly provided by Novartis, with purities of 99. 6, 97. 0 and 99. 7%, respectively. Stock solutions of each compound were prepared at 1 mg/mL in methanol and stored at -20°C. Blood sampling. In order to determine IM and CGP74588 concentrations, venous blood samples were collected during cycle 1 on D1, D10 and D14 at 0, 1, 2, 5, 8 and 24 h after drug administration. For each plasma sample, blood was collected in a tube containing heparin, inverted several times, centrifuged at 5,000 × g for 10 min and stored at -20°C.
25 mL/min. IM and CGP74588 were detected with the mass spectrometer operating in positive electrospray ionisation mode, using a capillary voltage, a cone voltage and a collision energy set at 3. 5 kV, 40 V and 25 eV, respectively. IM, CGP74588 and the [d8]-imatinib internal standard were detected by multiple reaction monitoring (MRM) using the transitions 494→394, 480→394 and 502→394, respectively. The concentrations of both compounds were quantified using Masslynx ® and Quanlynx ® software with a weighted (1/x 2 ) least-square linear calibration over the range set from 10 to 10,000 ng/mL. Nine plasma standards (10, 20, 50,  100, 200, 1000, 2000, 5000 and 10000 ng/mL) were prepared in duplicate each day. Quality control plasma samples (10, 200,  2000 and 4000 ng/mL) were prepared over three days.
Acknowledgments This work was supported by  Novartis SA, Institut National du Cancer (INCa) , la Ligue contre le cancer (LIGUE labelisée, L. Z. ), l' Association pour la Recherche sur le Cancer  (A. R. C. ),  Fondation pour la Recherche Médicale  and  Fondation de France. We acknowledge  Novartis  for providing chemicals used for pharmacokinetic analyses, i. e. , [d8]-imatinib and  N-desmethylimatinib  ( CGP74588 ). The authors thank  Lorna Saint Ange  ( Institut Gustave Roussy ) for editing. SH,  Back DJ , et al. The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC. Br J Pharmacol 2009; 156: 497-508 ; PMID:19154420; http://dx. doi. org/10. 1111/j. 1476-5381. 2008. 00050. x.
METHODS Study design. The Teriflunomide and Vaccination (TERIVA) study (NCT01403376) was a multicenter, multinational, parallel-group study involving 128 patients in 3 treatment groups. Groups 1 and 2 included patients with RMS treated with either teriflunomide 7 mg or 14 mg once daily for at least 6 months over the course of 2 long-term extension studies (NCT00228163: open-label extension of a phase II study, which started in 2001  5, 6  ; NCT00803049: blinded extension of the phase III TEMSO study, which started in 2004  3, 7, 8  ). Group 3 included patients with RMS who had received a stable dose of IFN-b-1 for at least 6 months, and represents a reference population of patients with RMS who have previously been reported to mount normal immune responses to seasonal influenza vaccination.
Materials Hoshizuka-4 strain is a multidrug resistant strain with mutation in the three main genes involved in M. leprae resistance to antibiotics: folP gene (P55S), involved in dapsone resistance; rpoB gene (S456L), involved in rifampicin resistance; and gyrA gene (A91V) involved in quinolones resistance (using numbering system of the M. leprae genome TN, GenBank nuNC002677). Briefly, Hoshizuka-4 strain was isolated from a patient who developed a lepromatous leprosy after repeated clinical relapses  [18]. He received dapsone, streptomycin, rifampin, clofazimine, isoniazid, ofloxacin and prothionamide to treat subsequent relapses. These drugs were administrated irregularly as monotherapy or in combinations, often at doses below recommended levels and standard multidrug therapy was never applied.
Data compiled from World Animal Health Information databases/OIE  [30, 31, 42]  and  [37, 38, 50, 59, 60]. In the East African region, the evidence generally suggests low prevalence of bTB in both wild  [49, 50]  and domestic animals, with notable exceptions in intensive husbandry systems (dairy) in some countries such as Ethiopia, Uganda and Tanzania  [51, 52]  and in pastoral systems in Uganda  [53, 54]. The spillover of bTB into humans in the region is poorly documented  [28] , and Ugandan studies report an above global average of ∼3% of human TB infection  [54] [55] [56]. In Ethiopia, despite the very high prevalence of extrapulmonary TB (EPBT) in humans, which is suggestive of bTB infection, M. bovis was only isolated in 4/964 EPTB patients  [52, 57]. Three out of 173 pulmonary TB patients were M.
Central Africa Boukary et al. [33]  recently reviewed bTB studies in domestic stocks in sub-Saharan Africa. Only seven studies were related to bTB in livestock in Central African countries, and the reported prevalence in individual cattle ranged from 0•2% to 19•9% depending on the surveillance method adopted. The results also depended on the age of the animals tested and the type of production system considered, and on the breed of cattle tested  [61] [62] [63]. No published information is available, to our knowledge, on bTB in wildlife populations, and according to the OIE database  [30]  only one 'suspected' bTB case in wildlife was reported (in Equatorial Guinea) for the period 2007-2012. Wild ungulates (including African buffalo) still persist mainly in savannah ecosystems of southern Chad, North Cameroon and the Republic of Central Africa, and these largely decimated populations may be exposed to bTB spillover from livestock.
West Africa Very little data has been published on bTB in wildlife for West African countries (Fig. 1b ). According to the OIE database  [30]  only one 'suspected' bTB case in wildlife was declared (in Niger) for the period 2007-2012. For livestock populations, the studies that have estimated bTB prevalence in West Africa revealed significant variations according to the areas and the production system considered  [33, [64] [65] [66]. Low bTB prevalence was estimated in the Torodi region of Niger (0•8% comparative intra-dermal skin test positive  [67] ) and at Bamako's abattoir in Mali (1•8% with symptomatic gross lesions  [68] ). The highest bTB prevalence in cattle was found in periurban areas, in Ghana (13•8% comparative intradermal skin test positive  [69] ) and in Mali (Bamako, 19% prevalence comparative intra-dermal skin test positive  [70] ).
ACKNOWLEDGEMENTS We thank the organizers of the 1st Wildlife Tuberculosis Conference, held 9-12 September 2012 in Kruger National Park,  South Africa , for the opportunity to gather first-hand information on the latest developments regarding wildlife bTB. This work was conducted within the framework of the  Research Platform 'Production and Conservation in Partnership'  ( RP-PCP ) and the  Animal and Human Health Environment and Development initiative (AHEAD). M. dG. W and A. C. were supported by the  Ministère Français des Affaires Etrangères  through the  French Embassy in Zimbabwe (RP-PCP grant   2008-2012 ), and R. T. by the  Swiss National Science Foundation.
GENOME-WIDE EXPRESSION COMPARISON BETWEEN INTRATUMORAL AND NON-TUMORAL NK CELLS Previous studies showed that NK cell phenotype and functions were altered in human lung tumors  (Platonova et al. , 2011). Gene expression profiling using Agilent microarray technology was performed to characterize the transcriptional signature of Tum-NK and Non-Tum-NK cells. Normalized signal values corresponding to the 42,405 probe-sets representing the whole genome were imported from microarrays data files. Probes (35,120) giving normalized signal values different from the background signal in at least half of the chips involved in the study were selected. To determine whether Tum-NK cells displayed a specific transcriptomic signature, a non-supervised clustering analysis (Spearman correlation similarity measure and ward linkage algorithm) with the normalized signal values of the 35,120 probe-sets was performed (Figure  2A ).
INTRATUMORAL NK CELLS DISPLAY GENE EXPRESSION SIGNATURE OF ACTIVATED CELLS To determine the immunological meaning of this gene expression profile, the most relevant functions related to genes modulated in Tum-NK were characterized using Ingenuity Pathway Analysis (IPA) application. Among the 1236 genes, 871 unique and predicted genes were successfully mapped to a gene in Ingenuity Pathways Knowledge Base (IPKB). Networks were then generated from these 871 genes to determine the associated functions including immune cell trafficking and inflammatory responses. The IPA software was used to assort the corresponding list of the top immunological functions based on the number of genes implicated and the p-value attributed to the variation of each gene expression (Table  2 ). The top functions found modulated in Tum-NK cells as compared to Non-Tum-NK cells included mainly movement and activation of leukocytes.
SCANNING AND DATA ANALYSIS Fluorescence signals of the hybridized Agilent Microarrays were detected using Agilent's Microarray Scanner System (Agilent Technologies). The Agilent Feature Extraction Software (FES) 10. 7. 3. 1 was used to read out and process the microarray image files. For determination of differential gene expression FES derived output data files were further analyzed using the Rosetta Resolver gene expression data analysis system (Rosetta Biosoftware, Rosetta error model;  Weng et al. , 2006).
STATISTICAL AND DATA ANALYSIS For each probe, the ratio of the average of fluorescence intensity (fold-change) was calculated for the Tum-NK related to the Non-Tum-NK samples. A "P50" list has been created by filtering probes flagged as "Present" for at least half of the chips involved in the study, and was used for the genome comparison. The group comparisons were done using Student's t -test. To estimate the false discovery rate the resulting p-values we filtered at 0. 05. Cluster analysis was performed by hierarchical clustering, using the Spearman correlation similarity measure and ward linkage algorithm. An unsupervised analysis step was performed using clustering prior to any supervised statistical comparison to unveil natural groups among the tested samples. Probes lists were filtered by p-value < 0.
ACKNOWLEDGMENTS This work was supported by the  Institut National du Cancer and (INCA  Grant No. 2011-1-PL BIO-06-INSERM 6-1  to Isabelle Cremer), the  Institut National de la Santé et de la Recherche Médicale , the  University Pierre et Marie Curie , and the  University Paris Descartes. We thank  Diane Damotte  and  Pierre Validire  for providing lung samples from  Hotel Dieu  hospital and  Institut Mutualiste Montsouris.
RNA interference represents a powerful approach for antitumor therapy by allowing in vivo silencing of essential genes for tumor progression and provides a promising alternative to traditional small molecule therapies. However, delivery of siRNAs still remains the most challenging step for the development of a siRNA-based therapy. The challenge includes efficient target gene silencing in the desired tissue while avoiding side effects such as immune response, toxicity and off-target silencing. In this context, the cationic linear polyethylenimine (PEI) is well known for its efficiency to transfect genes both in vitro and in vivo as it is involved in several clinical trials for the treatment of bladder cancer (http://clinicaltrials. gov/ct2/ show/NCT00595088), pancreatic ductal adenocarcinoma (http://clinicaltrials.
gov/ct2/show/NCT01274455) and multiple myeloma (http://clinicaltrials. gov/ct2/ show/NCT01435720?term=senesco&rank=1). In this study, we investigated its ability to deliver functional antitumoral siRNA. To this end, we have developed sticky siRNAs (ssiRNAs) that mimic gene structure through reversible concatemerization brought by sticky 3'-complementary overhangs  [32]. These modified siRNAs confer a higher stability to the complexes formed with linear PEI, thus increasing gene silencing efficiency both in vitro and in vivo, compared with standard siRNAs. We used this new technology to specifically target survivin and cyclin B1 in B16-F10 murine melanoma cells. Our results show that ssiRNAs are efficient to inhibit survivin and cyclin B1 expression in vitro and that a systemic treatment with ssiRNAs targeting these two genes is able to reduce both subcutaneous melanoma tumors and their lung metastases.
Branched DNA assay QuantiGene assay (Panomics, Santa Clara, CA, USA) was used to quantify the amount of mRNA in cells or lungs. Cells were lysed in 600 μl of 1 × lysis buffer and incubated for 30 min at 50°C. Lungs were lysed in 20 ml of tissue and cell lysis solution (Tebu, Le Perray-en-Yvelines, France), supplemented with 0. 15 mg/ml of K Proteinase (Sigma-Aldrich, St Louis, MO, USA) and incubated three times 5 min at 60°C with 10 s vortexing. A volume of 1-60 μl of cell or lung lysate was used for branched DNA (bDNA) assay. Probe set were designed using QuantiGene ProbeDesigner software. Target gene expression was assayed according to manufacturer recommendations. Target expression level was normalized to corresponding GAPDH expression from the same cell lysate.
Results and discussion in vitro ssiRNAs gene silencing efficiency in B16-F10 murine melanoma cells We used previously validated survivin and cyclin B1 siRNA sequences  [33, 34] , designed sticky siRNAs with these sequences by adding 3' complementary overhangs and first tested their silencing efficiency both at the mRNA and protein levels in B16-F10 cells. A sequence presenting no homology with mRNA databases was used as a negative control. Transfection of B16-F10 cells with jetPEI® and different concentrations of specific ssiRNAs ranging from 25 to 100 nM was performed and all led to a significant reduction of cyclin B1 and survivin mRNA  levels. The level of inhibition was optimal at 50 nM, N/P of 8 and 75 nM, N/P of 6 (Figure  1a  and b ). Indeed, both concentrations induced a 70 to 80% inhibition of the two target mRNA expression compared to control cells.
Data Analysis Sequencing reads from all libraries were mapped to the reference genome (MSU6. 0) using MAQ software with default parameters  [10]. Reads which could be mapped equally well to unique locations without mismatch or with less than two mismatches were retained for further analysis. Genomic regions associated with histone H3K9ac or OsSRT1-binding were identified using MACS software  [11] , in which default parameters (bandwidth, 300 bp; mfold, 32; p-value of 1. 00e-05) and largellocal = 5000 were set up to call peaks representing enriched H3K9Ac or OsSRT1 binding. Peaks in the gene body and the upstream and downstream 2 Kb regions were identified as histone H3K9ac or OsSRT1 binding. The transcription factors in the genome were classified according to PlantTFDB (http://planttfdb. cbi.
edu. cn/index. php?sp = Osj). Gene ontology classification provided in TIGR Rice Genome Annotation Project (http://rice. plantbiology. msu. edu/) was used to assign genes to a hierarchical biological process following the criteria of the Gene Ontology Consortium databases (http://www. geneontology. org/external2go/tigr2go), then the Web Gene Ontology Annotation Plotting tool WEGO was used to plot GO categories (http://wego. genomics. org. cn) [12]. The p-value of a particular pathway was calculated with Pearson's chi-squared test, then corrected by False discovery rate (FDR), with a FDR cutoff of 0. 05 as the significance threshold  [13]. The ChIP-seq data from this publication is submitted to the GEO database (accession number GSE40054). The accession number of OsSRT1 RNAi microarray is GSE71976.