dataesr/scientific-paragraphs-categorization huggingface dataset:
A fused-silica capillary column (BPX 70, 60 m×0. 25 mm i. d. , 0. 25 μm film; SGE) was used with hydrogen as a carrier gas (inlet pressure: 120 kPa). The split ratio was 1:33. The column temperature program was as follows: from 160 °C, the temperature increased to 180 °C at 1. 3 °C/min, and was maintained for 65 minutes before increasing at 25 °C/min to 230 °C, temperature that was maintained for 15 minutes. The injector and detector were maintained at 250 °C and 280 °C, respectively. GC peaks were integrated using Chromquest software (Thermofinnigan). FA were quantified using an internal standard (1 mg/mL in chloroform/methanol (2/1, v/v)) added at 10% of the lipid weight before the (trans)methylation procedure. ) ) The glyceride structure of lymph PL was achieved by phospholipase A2 (PLA 2 ) hydrolysis according to the Wolff et al  (30)  method, using PLA 2 from bee venom (600 -2400 U/g; 1U = 1 µEq FA/h; Sigma-Aldrich).
Characterization of lymph chylomicrons Lymph chylomicrons were analyzed in terms of particle size. Data revealed that the mean diameter of CM were comparable between the 3 groups (223 ± 28, 248 ± 46 and 227 ± 47 nm for TG n-3 , TG n- 3 +PL veg and TG veg +PL n-3 , respectively).
ACKNOWLEDGEMENTS The study was partly financially supported by the  French National Association for Research and Technology (ANRT ,  N° 2015/1182 ). Authors are grateful to Novastell and in particular  Thierry Coste  for providing Lecimarin F50, and also to Polaris for supplying fish oils. The authors also wish to thank  Axelle Grélard  from  Bordeaux University, CNRS ,  CBMN-UMR 5248 , for RMN analysis.
Superoxide dismutase (SOD) activity was quantified using the Beauchamp and Fridovich's  [26]  method, slightly modified by Oberley and Spitz  [27]. Catalase (Cat) activity in the skeletal muscle was determined using Johansson and Borg's  [28]  method, which uses H 2 O 2 as a substrate and formaldehyde as a standard. 2. 5. 3. Citrate Synthase Activity. Citrate synthase (CS) activity was assessed following the production of mercaptide ions spectrophotometrically at 412 nm by adding dinitrothiocyanobenzene (DTNB), acetyl-CoA, and oxaloacetic acid. 2. 6. Statistical Analysis. Data are expressed as the mean ± SEM. Statistical analyses were performed using GraphPad Prism 6 (GraphPad Software, La Jolla, CA, USA). Normality was checked using the Kolmogorov-Smirnov test. Student's t-test was used to compare exercise capacity between healthy and sickle mice.
Confocal conditions are met when the image of this analysis field diaphragm through the microscope objective perfectly coincides with the focus of the laser beam on the sample. Under these conditions, the experimental spatial resolution, measured on calibrated latex beads (2, 0. 6, and 0. 16 µm in diameter) labeled with the fluorescent probe fluorescein, is 0. 5 µm for the directions X, Y, and Z. Finally the fluorescence spectra were recorded after spectrograph dispersion, in the 380-630 region on a 1024 diode-intensified optical multichannel analyzer (Princeton Instruments, Inc. , Princeton, NJ) with a resolution of 0. 25 nm/diode. Each fluorescence emission spectrum was collected from 1 to 10 s. Data were stored and processed on an 80286 IBM PS/2 microcomputer using the Jobin-Yvon "Enhanced Prism" software.
Data extraction and management Two review authors independently extracted data and cross checked the extracted information on study characteristics, and included participants, interventions, and reported outcomes using a piloted, standardised data extraction form in the online software Covidence (DKdG, SL, IT). Any differences related to the data extraction were resolved by rechecking the full text of the study or by discussion. If study data were only available from figures, data were extracted by use of the validated software Plot Digitizer (plotdigitizer. sourceforge. net). 22 When study data were ambiguous or data were not reported in a form that could be used for formal comparison, we contacted the corresponding and first author of the original publication via email.
Assessment of risk of bias Two review authors independently assessed the risk of bias for each study. Any disagreements were resolved by discussion or a third author (JJM). For the risk of bias assessment of randomised controlled trials, we used the Cochrane risk of bias tool. 23 For non-randomised controlled trials, we used the ROBINS-I tool (risk of bias in non-randomised studies of interventions). 24 e planned to create funnel plots when data of 10 or more studies were available to assess the likelihood of dissemination bias. Since none of the meta-analyses included 10 studies or more, a thorough assessment of dissemination bias was not feasible.
Assessment of the certainty of the evidence We used the GRADE approach (grading of recommendations assessment, development, and evaluation) to assess the certainty of the evidence for the most relevant, available measures of all critical and important outcomes. 27 According to the GRADE approach, we classified the certainty of evidence in four categories: high, moderate, low, and very low certainty of evidence. The GRADE certainty assessment per outcome was documented in GRADE evidence profiles, together with the pooled effects for the interventions. We used GRADEpro GDT online software  28  to compile the evidence profiles. Assessments of the certainty of evidence for all outcomes were reviewed with the WHO Nutrition Guidance Expert Advisory Group Subgroup on Diet and Health as part of the WHO guideline development process.
94, 95% confidence interval -1445. 24    38  researchers reported narratively (that is, without numerical data) that there were no significant differences in energy intake between the stevia and placebo groups. Data from two nonrandomised controlled trials  45 46  (n=22) suggested no difference between the intervention and control groups for energy intake. One randomised controlled trial  29  investigated the effect of NSSs on energy intake in overweight populations trying to lose weight. In this study, mean daily energy intake was reported to be 548 kJ lower in the group receiving NSSs than in the group avoiding NSSs (95% confidence interval -692. 73 to -403. 27; n=128). In addition, no significant differences were observed for self control with respect to eating (mean difference -0. 20, 95% confidence interval -1.
Data from two non-randomised controlled trials  46 49  and one cross sectional study  72  showed no differences in sugar intake between the intervention and control groups. Two randomised controlled trials  31 32  investigated the effect of NSSs on preference for sweet taste or sugar intake in overweight populations trying to lose weight. The preference for sweet taste, as assessed by desire for sweets (measured on a 0-10 scale with higher values indicating increased desire), was slightly lower in the group receiving NSSs than in the group not receiving NSSs (mean difference -0. 2, 95% confidence interval -0. 34 to -0. 06; one study, n=186, moderate certainty of evidence). Sugar intake was similar between the groups after three years of follow-up (-0. 00 g, -0. 18 to 0. 18; one, n=186). 31.
83 Energy intake was 6711, 6640, or 7728 kJ daily with aspartame, saccharin, or sucrose in the preschool group, respectively, and 8100, 8284, and 9293 kJ for school age children, respectively. In one randomised controlled trial with overweight children involved in active weight loss, researchers assessed change in appetite as self reported adverse events, which were reported to be no different between the study groups (incidence rate ratio 0. 94, 95% confidence interval 0. 35 to 2. 49; one study, n=55, very low certainty of evidence). 86 reference for sweet taste-One crossover nonrandomised controlled trial  83  (n=47) reported significantly lower sugar intake in children receiving aspartame or saccharin than in children receiving sucrose (not enough data for formal statistical comparison, very low certainty of evidence).
Study planning should consider the duration necessary for plausible, relevant effects to occur in the different outcomes of interest. Longer term studies are needed to assess effects on overweight and obesity, risk for diabetes, cardiovascular disease, and kidney disease. Type and dose of sweetener use should be reported precisely and transparently in all studies. Precise reporting of sweetener content (that is, type and amount of sweeteners) in ready-to-consume foods and beverages is highly desirable and could be helped by more detailed information on ingredients as provided by manufacturers. Consistent use of core outcome measures and consensus on timing and mode of assessment would further help researchers pool data across studies. In addition to studying the effects on NSS use in a general healthy population of adults and children, research should focus on diseased populations and other subgroups, including pregnant women and their offspring and people who use NSSs in amounts higher than average (such as those with diabetes).
to 247. 36; three studies, n=276). In one randomised BMJ: first published as 10. 1136/bmj. k4718 on 2 January 2019. Downloaded from doi: 10. 1136/bmj. k4718 | BMJ 2019;364:k4718 | the bmj controlled trial, 13 030 911 Records identi ed through Additional records identi ed through database searching aer duplicates removed other sources aer duplicates removed 13 941 Records screened 12 970 Records excluded 971 Full text articles assessed for eligibility 895 Full text articles excluded 257 Wrong publication format 125 Study duration too short 117 Sweetener not de ned 101 Wrong study type 82 Not a primary human study 74 Wrong intervention 42 Wrong study population 30 No relevant health outcome described 20 No direct or concurrent comparison 17 Duplicate 14 Full text not available 16 Reason not recorded 57 Studies included in qualitative synthesis 56 Studies included in quantitative synthesis (meta-analysis) Fig 2 | PRISMA (preferred reporting items for systematic reviews and meta-analyses) flowchart of included studies 28 http://www.
What is the total length of distribution network covered by the WSP / ISO certification? Improved control of production and distribution processes Lack of access to supporting activities (e. g. education, training, technical support, consultancy) Financial means Database of hazards and control measures WSP: ISO 22000: 6. Please describe briefly the systems covered by the WSP / ISO 22000 certification (e. g. main treatment steps at the treatment plants, Better reactivity and management of alarms Other benefits (please specify): Lack of guidance materials Education / training programme Access to supporting activities Reduction in the number and severity of incidents in production / distribution Lack of financial support Education, training Common pool of internal auditors shared between BUs Consultancy Process optimization / improvement of infrastructure Improved procedures for management of water production / distribution Limited staff (time) to develop and implement WSPs Technical support Guidance material Responses to Frequently Asked Questions from auditors presence of re-chlorination in distribution system…) Improved application of procedures / good practices Limited qualification of staff to develop, implement and / or evaluate WSPs Cooperation with health agency Other (please specify): What were your expectations? Increased awareness, knowledge, understanding / implication of personnel Involvement of client (municipality) in WSP development Difficulty in understanding the requirements of the ISO 22000 standard Improved record keeping and data collection Development of a site-specific hazard analysis Difficulty in fixing the limits / level of detail of the hazard assessment Better targeting / prioritization of investments Other (please specify): Reluctance of personnel to changes Thorough, comprehensive and exhaustive hazard assessment of all treatment and distribution steps Lack of implication of sub-contractors Participation of all staff in system development IV Time and costs * Image / Communication Development of a system based on staff experience Lack of implication of suppliers (chemicals, materials, water purchase…) Improved image of professionalism / high level of service Decrease in customers complaints Lack of adequate equipment Development of a system perceived as simple, useful, applicable to day-to-day management of operations 1.
After washing, they were incubated with tyramide 0. 5% (Perkin Elmer, Waltham, Massachusetts) for 20 minutes and rinsed in 0. 02M KPBS. Sections were incubated with Alexa Fluor® 488 streptavidin (1:500) and the secondary antibody Alexa Fluor-conjugated goat antimouse (1:500; Abcam, Cambridge, UK) for 1 hour. The sections were then counterstained with Hoechst (Invitrogen) for 3 minutes at room temperature. The sections were finally put under cover slips slightly wet with buffered Mowiol mounting medium (Sigma Aldrich). Image processing. Tissue sections were analyzed and digitally photographed using a Zeiss Axio Imager Z2 apotome microscope mounted with an AxioCamMRm digital color camera (Carl Zeiss, Oberkochen, Germany) and AxioVision software (Carl Zeiss). To create photomontages, single-plane images were captured using the MosaiX module of the AxioVision 4.
6 system (Carl Zeiss) and a Zeiss 20 X objective (N. A. 0. 8) for each fluorophore sequentially. Images were subsequently adjusted for intensity and contrast using Photoshop software (Adobe, San Jose, California). Immunolabeling quantification. Cell counts were performed using the count tool of Photoshop (CS5. 0) software; pSTAT3positive-, ß-endorphin-positive, and double-labeled cells were manually counted on digitized images. For each animal, two hemisections of the tuberal region of the hypothalamus were counted by an investigator blind to the experimental condition, and the mean of the two counts was used for analysis. Counting was performed on a homogenous area on the 24 slices of interest (i. e. , two slices per animal for six HFD and six NFD minipigs, of which half had received leptin injection in each group).
Acknowledgments The authors thank  Dr. S. Rasika  for the editing of the manuscript and  Julie Kerr-Conte  and her whole team from the laboratory of biotherapies for diabetes, Inserm  U1190 , for their support and advice;  Michel Pottier ,  Arnold Dive ,  Audrey Quenon ,  Martin Fourdrinier , and  Nicolas Durieux  for MRI assessment; and  Maurice de Meulaere  from the laboratory of anatomy and  Martine Michiels  from the  Centre de Biologie et Pathologie, Centre Hospitalo-Universitaire de Lille , for their technical help. Obesity | VOLUME 27 | NUMBER 9 | JUNE 2019 www. obesityjournal. orgPreclinical  Minipig Model  of  CNS Leptin Transport Chmielewski  et al.
This work was supported by grants from the  Fond Français de l'Alimentation (FFA) , the  Société Française de Nutrition (SFN) , the  Institut Benjamin Delessert , the  Diamenord Association , and the  Agence Nationale de la Recherche  ( ANR-15-CE14-0025 ,  Glioshuttles4metabolism ; Distalz). declared no conflicts of interest. research studies; AC, AD, TH,.
Comparison between datasets further validated the pipeline and confirmed the alternative polyadenylation patterns of odorant receptors. Qualitative and quantitative analyses of the annotated 3′ regions demonstrate that 1) Odorant receptor 3'UTRs are longer than previously described in the literature; 2) More than 77% of odorant receptor mRNAs are subject to alternative polyadenylation, hence generating at least 2 detectable 3'UTR isoforms; 3) Splicing events in 3'UTRs are restricted to a limited subset of odorant receptor genes; and 4) Comparison between male and female data shows no sex-specific differences in odorant receptor 3'UTR isoforms. Conclusions: We demonstrated for the first time that odorant receptor genes are extensively subject to alternative polyadenylation. This ground-breaking change to the landscape of 3'UTR isoforms of Olfr mRNAs opens new avenues for investigating their respective functions, especially during the differentiation of olfactory sensory neurons.
In contrast, 3′ untranslated regions (3'UTRs) of Olfr mRNAs are as yet poorly documented in databases and rarely included in Olfr studies  [25] [26] [27]. The lack of knowledge regarding the 3'UTRs of Olfr mRNAs is detrimental, given the well-established critical functions of 3'UTRs in regulating mRNA stability/degradation, translation repression/activation and subcellular localization  [28]. Even more importantly, high throughput RNA sequencing during the past decade provided strong evidence for widespread alternative polyadenylation (APA) of mRNAs in eukaryotes, leading to the expression, for many genes, of several transcript isoforms with 3'UTRs of different lengths  [29]. This APA turned out to be dynamically regulated during development  [30] , with lengthening or shortening of 3'UTR isoforms as an organism develops or a neuronal cell population differentiates  [31] [32] [33].
At the subcellular level within developing neurons, APA is used to produce different mRNA isoforms having specific localization (i. e. axonal vs. cell body localization  [34] [35] [36] [37] [38] ). Furthermore, it was shown that APA is regulated in an activity dependent manner in adult neurons  [39] , where alternative 3'UTRs modify the localization, regulatory potential and plasticity of mRNAs in neuronal compartments  [30]. To document the 3'UTRs of Olfr mRNAs in the mouse, and to determine to what extent these mRNAs are subject to APA, we developed a dedicated strategy based on computational analyses of previously published RNA-Seq datasets obtained from adult mouse whole olfactory mucosa  [26, 40]. Given that Olfr genes constitute the largest gene family in mammalian genomes (including around ~1400 Olfr genes or pseudogenes in the mouse genome  [3] ), a high throughput approach was required.
In the present study, we re-analyzed Ibarra-Soria's dataset with the Isoform Structural Change Model (IsoSCM) method, dedicated to 3'UTR annotation in ab initio assemblies  [41] , and compared with the Cufflinks method. The parameters for the reads alignment and annotation steps were set to optimize the accurate and comprehensive identification of the Olfr 3'UTR ends. In addition, we validated the annotations obtained for selected representative Olfr genes by independent experimental characterizations.
Results Current documentation on Olfr 3'UTRs is not consistent, and likely underestimates their diversity Until recently, most Olfr genes in databases showed no 3'UTR sequences. As an example, only 17 or 5 Olfr genes have one or multiple polyadenylation sites described in their annotated 3'UTR or extended 3′ region in 2 databases specific for 3'UTRs, PolyA_DB 3  [42]  or APADB  [43] , respectively. Improved annotations of Olfr 3'UTR sequences were generated from male and female OM RNA-Seq data produced by Ibarra-Soria and colleagues  [26]. In 2015, Shum and colleagues published a study focused on the analysis of Olfr 3'UTRs and established a description of the 3'UTRs for 554 Olfr genes from adult female whole OM RNA-Seq data  [27]. At the end of 2016, gene models for mouse Olfr genes were updated by the Havana project based on Ibarra-Soria's RNA-Seq data (Ensembl 87 release  [44, 45] ), and Olfr genes now have 3′ annotations in mouse genome databases.
However, these 3′ annotations are not fully consistent with either the Shum or the Ibarra-Soria analyses. As an example, in the Ensembl database, Olfr1507 (also known as MOR28 or MOR244. 1) shows 2 alternative 3'UTRs, one described by Ibarra-Soria and colleagues, and the other by Shum and colleagues (Fig. 1a ). A third isoform identified by Ibarra-Soria et al. , however, is excluded from the database. In the same Ensembl database, Olfr15 (also known as MOR256. 17) shows a single 3'UTR, described by Ibarra-Soria et al. , whereas Shum et al. demonstrated a shorter 3'UTR for this Olfr (Fig. 1a ). In this latter work, an alternative 3'UTR was mentioned for Olfr15, but not described (Additional file 3: Table  S2  in  [27] ). In an attempt to clarify this issue, we went back to the raw data of Ibarra-Soria and colleagues  [26] , and noticed that there were discrepancies between the 3′ annotations and the RNA-Seq data.
In addition to the ambiguity described above, the number of alternative 3'UTRs clearly seems underestimated in both studies. This problem is likely due to the fact that both RNA-Seq analyses used Cufflinks for annotation, which in the literature  [41]  appears inefficient for the identification of alternative RNA ends. Thus, we decided to test dedicated tools and to set up a workflow specifically designed for the accurate characterization of the 3'UTRs of Olfr mRNAs. We applied this approach to available RNA-Seq datasets from first adult male OM, and then adult female OM. Implementation of a dedicated computational pipeline to document the 3'UTR repertoire of mouse Olfr mRNAs Our workflow comprises 6 steps ultimately leading to the identification and relative quantification of all   S3  in this paper).
A B detectable Olfr 3'UTR isoforms (Fig. 2 , see methods for a complete description). Briefly, we chose to base our computational pipeline on STAR software for alignment (Fig. 2 , Step 1). Before the assembly step, we applied a mask restricted to genomic regions of Olfr genes, most of them being included in large genomic clusters  [14, 15, 18, 46, 47]  (Fig. 2 , steps 2 and 3; Additional file 1: Table  S1 ). In step 4, the IsoSCM algorithm was used for 3′ annotations. IsoSCM is an ab initio transcript assembly method implementing multiple change-point inference in terminal exon models  [41]. IsoSCM distinguishes between local drops of coverage (due to biases) and sustained decrease of coverage (exon boundary changepoint), and it avoids fragmentation due to small gaps in coverage. Among the available methods for 3'UTR annotation from RNA-Seq data, we chose IsoSCM for the following reasons: it allows more than two 3'UTRs per gene (as compared to PHMM method  [48] ), it is able to detect novel polyA sites independently of genome annotation (as compared to the DaPars  [49, 50] , 3USS  [51] , Roar  [52] , QAPA  [53]  or TAPAS  [54]  reference-based methods), it is based on change-point analysis (as compared to GETUTR  [55] , based on read coverage smoothing), it is not focused on samples comparison (as compared to ChangePoint  [56] ) and it is not dependent on 3'end sequencing (as compared to the IntMAP  [57]  or CSI-UTR  [58]  integrative methods).
The optimization of key parameters of IsoSCM to reach a compromise between sensitivity and specificity are detailed in the methods section, and Additional file 2: Figure  S1. In parallel, the data were processed in step 4 with the Cufflinks assembly method, to allow comparison with a previous study aiming at annotating the Olfr 3'UTRs  [27]. In Step 5, transcripts were reconstructed. Furthermore, because 3'UTR ends depend on the presence of functional polyadenylation (polyA) signals (PAS)  [59] , we implemented in the workflow a search for canonical PAS in the vicinity of the newly identified 3'ends (Fig. 2 , step 5). Finally, for each Olfr gene, we used the quantitative coverage data (counts) in the different segments defined by the alternative 3′ ends downstream of the stop codon, and their respective length, to estimate the relative abundance of each 3'UTR isoform among the entire mRNA population (Fig.