dataesr/scientific-paragraphs-categorization huggingface dataset:
LPE but not PMPE was able to reduce the release of lactate at comparable doses found in intact TB-PE (Figure  7A ). Cell viability was not modified either by PMPE or LPE treatment at 1x or 2x doses  (Figure 7B and S4D). In line with the reduction of lactate, LPE also inhibited HIF-1α expression (Figure  7C ), partially decreased mROS production by M1 macrophages (Figure  7D ), and rendered the IFN-γ-activated macrophages more susceptible to Mtb intracellular growth (Figure  7E ). To determine whether metabolic-active lipids found in TB-PE were bacterial or hostderived, we performed a lipidomic analysis of the LPE. Mass spectrometry signals corresponding to the main mycobacterial lipid families were not detected in the TB-PE lipid extract dataset, according to MycoMass and MycoMap databases  (Layre et al.
The macrophage population was gated according to its Forward and Size Scatter properties. The median fluorescence intensity (MFI) was analyzed using FCS Express V3 software (De Novo Software, Los Angeles, CA, USA). For mice experiments, cell surface staining of single-cell suspensions from lungs was performed using fluorophore-conjugated antibodies: CD45. 2, MERTK (clone DS5MMER), SIGLEC-F (clone E50-2440), CD64 (clone 10. 1), Ly6G (RB6-8C5), CD11c (clone N418), CD11b (clone M1/70) and Live/Dead (LIVE/DEAD™ Fixable Aqua Dead Cell, Thermofisher Scientific). For analysis of mitochondrial markers, cells were stained with MitoSOX Red (5μM) and DiOC6 (40nM) (ThermoFisher) at 37°C for 30 min. Cell staining was analyzed using a FACSAria Fusion cytometer in BSL3 facility and FlowJo software version V10.
Fluorescence microscopy Cells were stained with 250 nM MitoSpy Green FM (Biolegend) for 30 minutes. The cells were then washed with PBS three times. All the samples were imaged on a FluoView FV1000 confocal microscope (Olympus, Tokyo, Japan) equipped with a Plapon 60X/NA1. 42 objective. To quantify the mitochondrial morphology of MitoSpy Green FM-stained macrophages, we developed a computer-aided analysis tool scoring the mitochondrial length and number per cell with ImageJ-Fiji software. Briefly, we used a motorized z-focus to obtain 3D images spanning the entire height of blindly selected cells to capture the entire architecture of the mitochondrial network and combined them into a single image using a maximum intensity projection. A threshold was defined to identify mitochondria based on their fluorescence intensity, and images wereskeletonized' to measure mitochondrial length (perimeter) and number.
After extensive washing, blots were incubated with a horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG Ab (1:5000 dilution; Santa Cruz Biotechnology) for 1 h at room temperature. Immunoreactivity was detected using ECL Western Blotting Substrate (Pierce). Protein bands were visualized using Kodak Medical X-Ray General Purpose Film. For internal loading controls, membranes were stripped by incubating in buffer consisting of 1. 5% Glycine, 0. 1% SDS, 1% Tween-20, pH 2. 2 for 10 minutes twice, extensively washed and reprobed with anti-βactin (1:2000 dilution; ThermoFisher, clone AC-15) and or HRP-conjugated goat antimouse IgG Ab (1:2000 dilution; Santa Cruz Biotechnology). Results from Western blot were analyzed by densitometric analysis (Image J software).
Visualization and quantification of Mtb infection Macrophages seeded on glass coverslips within a 24-well tissue culture plate at a density of 5 × 10 5 cells/ml were infected with the red fluorescent protein (RFP) expressing Mtb CDC 1551 strain at a MOI of 5:1 during 2 h at 37°C. Then, extracellular bacteria were removed gently by washing with pre-warmed PBS, and cells were cultured in RPMI-1640 medium supplemented with 10% FBS for 48 h. The glass coverslips were fixed with PFA 4% and stained with BODIPY 493/503 (Life Technologies). Finally, slides were mounted and visualized with a FluoView FV1000 confocal microscope (Olympus, Tokyo, Japan) equipped with a Plapon 60X/NA1. 42 objective, and analyzed with the software ImageJ-Fiji. We measured the occupied area with RFP-Mtb (expressed as Raw Integrated Density) per cell in z-stacks from confocal laser scanning microscopy images.
ACKNOWLEDGMENTS We thank  Alison Charton  for her key help in the in vivo experiments, the  TRI-IPBS platform  ( Emmanuelle Naser  and  Antonio Peixoto ) for flow cytometry and image analyses, the  ANEXPLO-IPBS platform (Flavie Moreau and Céline Berrone)  for maintenance of ASB3 facility and BSL3 multi-pathogen facility, and the  MetaToul Lipidomic Core Facility  ( I2MC, Inserm 1048, Toulouse, France, MetaboHUB- ANR-11-INSB-0010 ), for assistance and access to the mass spectrometer instrument. In addition, we are grateful for the editing service provided by Life Science editors. This work was supported by the  Argentinean National Agency of Promotion of Science and Technology  ( PICT-2015-0055  to MCS and  PICT-2017-1317  to LB), the  Argentinean National Council of Scientific and Technical Investigations (CONICET ,  PIP 112-2013-0100202  to MCS), and  CONACYT/CONICET , the  National Council for Science and Technology Mexico  ( CONACyT   FC 2015-1/115  to  MCS and CST) , the  Centre National de la Recherche Scientifique , the  Université Toulouse-III Paul Sabatier , the  Agence Nationale de la Recherche  ( ANR-18-CE15-0004-01  to DH),  Fondation pour la Recherche Medicale  ( ING20160435108  to EL), and the  Agence Nationale de Recherche sur le Sida et les Hépatites Virales  ( ANRS2014-CI-2 ,  ANRS2014-049  to ON, and  ANRS 2020-1  to CV and GL-V).
The aim of this study was to conduct a systematic review and meta-analysis on the effectiveness of interventions to increase children's water consumption. A systematic literature search was conducted in seven electronic databases. Studies published in English before 18 February 2019 that evaluated any type of intervention that measured change in water consumption among children aged 2 to 12 years by applying any type of design were included. Of the 47 interventions included in the systematic review, 24 reported a statistically significant increase in water consumption. Twentyfour interventions (17 randomized controlled trials and seven studies with other controlled designs) were included in the meta-analysis. On average, children in intervention groups consumed 29 mL/d (confidence interval [CI] = 13-46 mL/d) more water than did children in control groups.
(c) We included any type of intervention strategy that aimed to promote water consumption among children. For studies that had a control group, the control group was defined as children who were not exposed to the intervention designed to promote water consumption. (d) We included the following categories of water: tap water, bottled drinking water, unflavoured sparkling water, flavoured water (nonsweetened), or any other source of safe drinking water. (e) We included studies that were published in an English-language peer-reviewed journal anytime up to 18 February 2019. The main exclusion criteria that were applied during the selection process were as follows: (a) studies that only included participants from clinical populations (eg, obesity, malnutrition, and gastroenteritis), as we focused on the general population; (b) studies with data of less than 10 participants; and (3) studies that did not use human subjects.
| Data extraction After discussion and consensus among the study team, a standardized data extraction form was developed. This form was used to extract data from the studies by one researcher (C. F. ). The information that was extracted included author, year and country of study, study design and name, intervention content (setting, strategy, socioecological level targeted, focus, frequency, and theory used), control condition, length of intervention and follow-up time, population age and characteristics, number of participants in intervention and control groups and number of clusters (if applicable), how water consumption was measured, participation and retention rate, and outcome data: For the purpose of the meta-analysis, continuous data were extracted either as mean with standard deviation or as adjusted mean difference with standard error.
The meta-analysis was conducted in Review Manager (version 5. 3, Cochrane Library). The Cochrane Handbook was used for guidance regarding missing data and combining of data,  41  and the Cochrane calculator was used for making calculations. Results from the most adjusted models were used, wherever available. If the mean difference in water consumption between the control group and intervention group at follow-up was not reported, the mean water consumption at follow-up was extracted separately for the intervention group and control group, and the mean difference between intervention and control group was calculated. Using follow-up scores instead of change from baseline to follow-up scores is suggested to generate more conservative results in meta-analyses. 33, 47  in the paper water consumption was reported in a different quantity than in millilitres or within a different time period than 1 day, consumption was recalculated to millilitres of water per day.
| Strengths and limitations To the best of our knowledge, this was the first systematic review and meta-analysis that focused solely on the effectiveness of interventions in promoting water consumption among children aged 2 to 12 years. The literature search was performed in seven databases, and a rigorous procedure was followed for the inclusion of studies in our review. 101 However, our review also has some limitations that must be acknowledged. We included RCTs, non-RCTs, and other quasiexperimental designs in our systematic review and meta-analysis. Non-RCTs and other quasi-experimental designs are considered to provide lower-quality evidence and more often show significant results than are RCTs when there are none. We found a lower effect in RCTs compared with other controlled designs in our meta-analysis, although this difference was not significant.
Search strategy A systematic literature search for relevant studies was conducted in seven electronic databases: Embase, Medline Ovid, Web of Science, Cochrane, PsycINFO Ovid, CINAHL EBSCOhost, and Google Scholar on 11 May 2018. 30 This search was updated in all seven electronic databases on 18 February 2019. A combination of key words was used in the search: (water or beverage* or drink* or related key words) and (child* or infant* or toddler* or related key words) and (intervention* or trial* or strateg* or effect* or promot* or related key words). The search strategy was adapted to each database. The full search strategies are presented in the Supporting Information. In addition to the database search, references of relevant articles were screened for other studies. The systematic review protocol for this study was registered in the PROSPERO registry under registration number CRD42019124808 on 18 April 2019.
flow chart (Figure 1). A total of 35 912 records were identified through the database search. After removal of duplicates, a total of 19 346 records remained. After all rounds of screening, 39 articles were identified and included. Eight additional studies F I G U R E 1 Flow chart for the selection of reviewed studies T A B L E 1 Characteristics of the studies included in the systematic review (N = 47) Characteristics n (%) studies Study location a.
2 | METHODS 2. 1 | 221 Search strategy A systematic literature search for relevant studies was conducted in seven electronic databases: Embase, Medline Ovid, Web of Science, Cochrane, PsycINFO Ovid, CINAHL EBSCOhost, and Google Scholar on 11 May 2018. 30 This search was updated in all seven electronic databases on 18 February 2019. A combination of key words was used in the search: (water or beverage* or drink* or related key words) and (child* or infant* or toddler* or related key words) and (intervention* or trial* or strateg* or effect* or promot* or related key words). The search strategy was adapted to each database. The full search strategies are presented in the Supporting Information. In addition to the database search, references of relevant articles were screened for other studies.
X-ray Crystallography. Single-crystal X-ray diffraction data were collected at 183(1) K on a Rigaku OD XtaLAB Synergy, Dualflex, Pilatus 200K diffractometer using a single wavelength Xray source (Mo Kα radiation: λ = 0. 71073 Å) 103 from a micro-focus sealed X-ray tube and an Oxford liquid-nitrogen Cryostream cooler. The selected suitable single crystal was mounted using polybutene oil on a flexible loop fixed on a goniometer head and transferred to the diffractometer. Pre-experiment, data collection, data reduction and analytical absorption correction  104  were performed with the program suite CrysAlisPro. 105 Using Olex2,  106  the structure was solved with the SHELXT 107 small molecule structure solution program and refined with the SHELXL program package  108  (version 2018/3) by full-matrix least-squares minimization on F 2.
EPR. Electron paramagnetic resonance (EPR) experiments were performed on a MiniScope MS400 table-top X-band spectrometer from Magnettech. Simulation of the experimental EPR spectra was performed with the MATLAB EasySpin program. 110 All samples were dissolved in dry and N2-saturated DCM at a concentration of ca. 1 mM. Oxidized forms were generated using 1,1'-diacetylferrocenium hexafluoroantimonate (Ac2FcSbF6, E1/2 = 0. 940 V vs SCE in DMF/0. 1 M NBu4PF6). 70, 71 Chemical reduction was achieved by using cobaltocene (Cp2Co, E1/2 = -0. 880 V vs SCE in DMF/0. 1 M NBu4PF6). 70.
Treatment of 3D HeLa MCTS. HeLa MCTS after 4 days of growing at 37 °C and 5 % CO2 were treated by replacing half of the medium in the well with increasing concentration of compounds for 48 h in the dark. For untreated reference MCTS, half of the medium was replaced by fresh medium only. The cytotoxicity was measured by ATP concentration with CellTiter-Glo ® Cell viability kit (Promega, USA). CellTiter Glo® viability Test. Cell viability for MCTS was performed via ATP assay using luciferase. CellTiter-Glo® kit from Promega was used. The spheroids were incubated for 1 h after replacing half of the media with CellTiter-Glo reagent and the luminescence of the plate was read by SpectraMax M5 microplate reader. IC50 values were calculated using GraphPad Prism software. HeLa MCTS growth inhibition.
MCTS were grown and treated as previously described (see above). MCTS sizes were observed under a light microscope and pictures were taken with a Samsung Galaxy A5 2017 SM-A520FZKAXEF thanks to a phone microscope adaptor. Before imaging, the plate was sheken and half of the media was exchanged to remove dead cells. Images were recorded before treatment (day 0) and at day 3, 6, 9 and 13 after treatment. Pictures were first processed using GIMP a cross-platform image editor with a batch automation plug-in. The MCTS sizes were then calculated with SpheroidSizer, a MATLAB-based and open-source software application to measure the size of tumour spheroids automatically and accurately. Data analysis was done using GraphPad Prism software.
ICP-MS studies All ICP-MS measurements were performed on an high resolution ICP-MS (Element II, ThermoScientific) located at the Institut de physique du globe de Paris (France). The monitored isotopes are  101  Ru and 195 Pt. Daily, prior to the analytical sequence, the instrument was first tuned to produce maximum sensitivity and stability while also maintaining low uranium oxide formation (UO/U ≤ 5%). The data were treated as follow: intensities were converted into concentrations using uFREASI (user-FRiendly Elemental dAta proceSsIng ). 112 This software, made for HR-ICP-MS users community, is free and available on http://www. ipgp. fr/~tharaud/uFREASI.
Acknowledgements This work was financially supported by an  ERC   Consolidator Grant PhotoMedMet  to  G. G. ( GA 681679 ) and has received support under the program Investissements d'Avenir launched by the  French Government  and implemented by the  ANR  with the reference  ANR-10-IDEX-0001-02 PSL  (G. G. ). This work was financed by the  Swiss National Science Foundation  (Professorships  N° PP00P2_133568  and  PP00P2_157545  to G. G. ), the  University of Zurich  (G. G), the  Novartis Jubilee Foundation  (G. G and R. R. ), the  Forschungskredit of the University of Zurich  (R. R. ), the  UBS Promedica Stiftung  (G. G and R. R. ) and the  Charles University program  Progres  Q40/01. Ile de France Region  is gratefully acknowledged for financial support of 500  MHz NMR spectrometer of Chimie-ParisTech  in the framework of the  SESAME  equipment project.
Statistical analysis Descriptive analysis of the data collected during each patient evaluation will be carried up until the final evaluation. Specific time points for analysis in the three groups are: baseline; at 1 month after the last rTMS or sham sessions; and 12 and 24 months after the end of the first rTMS or sham course. Continuous variables will be described using median, standard deviation, minimal, maximal, and range for quantitative variables; qualitative variables will be described using frequencies and percentages. No data about quality of life, healthcare consumed, and the cost are available in the literature for this indication, making a priori the calculation of number of individuals needed impossible. The number of participants required for the present study was calculated according to the expected and sustained response in each arm (> 50% decrease in MADRS total score).
Tables will present differences between the three groups including their costs, QALY, and ICER. The ICER is calculated to consider the possibilities of vast dominance between these strategies  [55]. For example, the ICER between arms A and C will be calculated as follows: ICER ¼ C armA -C armC QALYs armA -QALYs armC C armA and C armC correspond to the costs of depression in each arm and are the QALYs' gain associated with the rTMS maintenance versus usual cares without rTMS (placebo). At the end, a univariate and determinate sensibility analysis will be estimate with the Tornado method to evaluate the robustness of the resultants concerning the variation in the cost of rTMS sessions and the hypothesis of their pricing. To estimate the costs of depression, clinical data matching the eCRF and the NHSD will be applied using the patient identification number.
These data are ideally obtained from the literature or a pilot study. However, no source data were available for our study concerning the costs and the quality of life in depression. Moreover, there is no official recommendation available on the QALY monetary value in France  [56]. That is why we preferred to calculate the number of individuals required according clinical criterion, the rate of response at 12 months, rather than a risky health economic hypothesis. This rate of response after the rTMS cure is estimated at 60% in arms A and B, based on the same rTMS protocol already used in French context in that population  [48]. According to the literature, we adopted a hypothesis of 30% of sustained response at 1 year in arm A  [23, 31, 49, 50]  and in arm B  [23, 49, 51, 52] , and n hypothesis of 11% rate of response sustained at 1 year in arm C  [53].
Potential explanatory variables to evaluate the depression economic cost are: formal and informal cares consumption (eCRF questionnaire); depression's socioprofessional aftermath with the Work Productivity and Activity Impairment (WPAI) [45]  and eCRF questionnaire; health economic analysis with micro-costing; and data extracted from the National Health System Database of Health (NHSD) with the French hospital expenditure database (E. U. Program of Medicalization of Information Systems [PMSI]). Data from the NHSD include: medical consultations; hospitalizations; pharmacological treatments; work stoppages; daily allowances; care-related transports; imagery and biology; nursing cares; and losses of production in association with the WPAI. Interventions Multiple rTMS devices are available in France: Magpro R30 or X100; Magstim Neurostar; Tamas; Powermag; or NBT.
Acknowledgements The authors wish to thank the  ACOUSTIM investigators Group  for their support and inclusion effort:  Jérôme Attal ,  Jean-Marie Batail ,  René Benadhira ,  Djamila Bennabi ,  Caroline Berjamin ,  Maxime Bonnin ,  Noomane Bouaziz ,  Jérôme Brunelin ,  Maxime Bubrovszky ,  Benjamin Calvet ,  Irina-Alexandra Catana ,  Macarena Cuenca ,  Gaelle Dall'Igna ,  Dominique Drapier ,  Laurine Egreteau ,  Wissam El-Hage ,  Filipe Galvao ,  Ghina Germaneau ,  Bénédicte Gohier ,  Emmanual Haffen ,  Ghassan Harika ,  Guillaume Ifrah ,  Némat Jaafari ,  Isabelle Jalenques ,  Dominique Januel ,  Redwan Maatoug ,  Bruno Millet ,  Clément Nathou ,  Benjamin Petit ,  Damien Pierre ,  Marion Plaze ,  Emmanuel Poulet ,  Gabriel Robert ,  Maud Rotharmel ,  Marine Rozet ,  David Szekely ,  Simon Taib ,  Benoît Trojak , and  Antoine Yrondi.
Study design The "ACute and Chronic Effects of Saxagliptin" (ACCES) study is a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study conducted at Jean Verdier University Hospital (Bondy, France). The study was approved both by the local ethics committee (Comité de Protection des Personnes, Reference Number: JLD/AP-protocole  and the French National Agency for Drug Security (Agence Nationale de Sécurité du Médicament, Number: A110912  -14)  and was registered as a clinical trial (NumberEudraCT: NCT01521312). There were two parts in this study. The rst one explored acute and long-term effects of saxagliptin vs placebo on glucose tolerance (ACCES-Glucose study), the results of which will be reported elsewhere. The second part explored the effects of saxagliptin vs placebo on vascular parameters (ACCES-Vasc study) which are shown in the present article.
We here found no detrimental effect of saxagliptin on myocardial function in our patients with IGT, when the Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus study had found an increased risk of hospitalization for heart failure in patients who were at high cardiovascular risk  (18, 19). We used trans-thoracic bio-impedance cardiography to measure hemodynamic parameters including stroke volume, cardiac output, left ventricular ejection time, left ventricular work index and thoracic uid content. The validity of this method against several reference methods and its clinical utility were reported in heart failure patients  (29). Neither at fasting nor post-prandially our data showed any signi cant difference for these parameters between saxagliptin and placebo treatment.
The Kaskawulsh Glacier is an iconic outlet draining the icefields of the St. Elias Mountains in Yukon, Canada. We determine and attempt to interpret its catchment-wide mass budget since 2007. Using SPOT5/6/7 data we estimate a 2007-18 geodetic balance of -0. 46 ± 0. 17 m w. e. a -1. We then compute balance fluxes and observed ice fluxes at nine flux gates to examine the discrepancy between the climatic mass balance and internal mass redistribution by glacier flow. Balance fluxes are computed using a fully distributed mass-balance model driven by downscaled and bias-corrected climate-reanalysis data. Observed fluxes are calculated using NASA ITS_LIVE surface velocities and glacier cross-sectional areas derived from ice-penetrating radar data. We find the glacier is still in the early stages of dynamic adjustment to its mass imbalance.