dataesr/scientific-paragraphs-categorization huggingface dataset:
Ultra High Performance Liquid Chromatography (UHPLC) To confirm the HPTLC results, LC analysis was conducted on a subset of six varieties representing the genetic diversity of the species (2 accessions of TD, 2 acc. of N, 2 acc. of W). UHPLC-DAD-ESI-MS/MS (Q/TOF) analyses were performed on an Agilent Infinity ® 1290 system (Agilent Technologies, Santa Clara, CA, USA) coupled to a UV/vis DAD detector and equipped with a QTOF 6530 detector (Agilent) controlled by MassHunter ® software (version B. 08. 00, Agilent, Santa Clara, CA, USA). Analytic separation was carried out on a Poroshell ® 120 EC-C18 column (100 mm × 3. 0 mm, 2. 7 µm) equipped with a pre-column (Poroshell ® 20 EC-C18, 5 mm × 3. 0 mm, 2. 7 µm). A gradient of 0. 4% formic acid in water (A) and acetonitrile (B) was used as follows: 0 min, 1% B; 1.
Statistical Analyses For HPTLC repeatability accuracy assessment, linear ranges were computed using the least squares method. Repeatability was confirmed by applying five repetitions of each standard at five different concentration levels (0. 1, 0. 2, 0. 3, 0. 4, and 0. 5 µL) and the variance among repetitions was expressed as the repeatability standard deviation (%RSD). The repeatability was assessed over 3 days using the same standard solutions. Peak area measurements (in area units, AU) were compared to individual standards and corresponding values were quantified in mg/g DW. Raw data (peak areas and their transformation in %DW) were recorded using Excel TM (Microsoft Corporation) spreadsheet format (see Table  S1 , Supplementary Materials). Statistical analyses were performed using ExcelStat software (Microsoft, Redmond, WA, USA) for linearity curves, normality of distribution tests, and principal components analysis (PCA, Spearman coefficients of correlation, mean standard deviation, and ANOVA Fisher's test of Least Significant Difference (LSD) at p ≤ 0.
Acknowledgements L. L. and A. M. thank the  Agence Nationale de la Recherche  ( ANRs SweetCat and Oxycarb ) for PhD grants. S. T. and Y. B. acknowledge the  European Union (ERDF) ,  RØgion Nouvelle Aquitaine  and the  University of Poitiers  for financial support. R. G. and J. J. B. acknowledge the  European Research Council  for generous support ( ERC-2013-StG Starting Grant  to RG-Project number  336376-ChMiFluorS  and  ERC-2017-AdG  to JJB-Project number  788143-RECGLYCANMR ). A. A. and J. J. B. thank  Agencia Estatal de Investigación( Spain)  for grants  CTQ2015-64597-C2-1-P  and  Severo Ochoa Excellence Accreditation   SEV-2016-0644. We thank  Dr. Gonzalo JimØnez-OsØsa  nd  Dr. T ammo Diercks  ( CIC bioGUNE ) for insightful discussions on the calculations for the SbF 6 À species and the scalar relaxation effects,respectively.
Acknowledgements This work was supported by the  European Union 's  Horizon 2020 research and innovation programme   under Marie Skłodowska Curie  grant agreement no. 642028  (NABBA). The authors thank  Pierre-Olivier Couraud ,  Université Rene Descartes , for providing the hCMEC/D3 cells, and  Stéphanie Nicolaÿ  for mass spectrometry analyses ( Service d'Analyses des Médicaments et Métabolites (Institut Paris-Sud d'Innovation Therapeutique (IPSIT)) ,  Université Paris-Sud ). Arkema is acknowledged for kindly providing the SG1 nitroxide. CNRS and  Université Paris-Sud  are also acknowledged for financial support.
Study design The literature review was performed according to the PRISMA method  [21]. The main databases in health sciences (PubMed) and in economics (EconLit and the National Health Service Economic Evaluation Database -NHSEED) were queried over a 10-year period (between February 2007 and February 2017), without limitation of location. A combination of the following search terms was used: • cost OR expenditure; • unnecessary OR misuse OR overuse OR inappropriate OR underuse; • antibacterial agent. Articles published in a language other than French, English, Spanish, and Portuguese were excluded from the study.
Selection of studies A two-step selection of studies was implemented: reading of titles and abstracts, followed by reading of the selected documents in their entirety. Reading of titles and abstracts led to selecting documents that addressed one of the following criteria for inclusion: (1) evaluation of costs associated with antibiotic misuse in a healthcare facility, or (2) evaluation of costs avoided as a result of the implementation of new practices (e. g. , diagnostic tests) or recommendations for proper use (e. g. , information campaigns among healthcare professionals) in healthcare facilities. Reading of the selected articles in their entirety led to identifying methodological elements used for the valuation of resources in monetary units. The main data extracted from the documents included in the final analysis was: -situations of misuse identified; -main objective and study perspective; -study methodology (i.
Results A total of 403 studies were retrieved from the databases. After elimination of duplicates, 402 articles were selected. After reading the titles and abstracts, 93 articles were selected. After reading articles in their entirety, 35 were included in the final analysis (Figure  1 ). A third of selected studies were performed in Asia (n=12, of which four in China) and a third in North America (n=12, of which eight in the United States). Furthermore, 70% of studies were performed in the past five years. A single study was performed in France  [25] , out of eight European studies. Six of the 35 selected studies were observational studies and 29 were interventional studies.
Limitations The initial literature analysis could have been more focused by adding the search term "hospital". Nonetheless, the choice not to restrict the search in this regard allowed for identification of potentially relevant studies performed in a broader setting (community and hospital settings). Furthermore, other databases (e. g. , Scopus, Embase, and NosoBase), as well as the grey literature, could also be explored to verify the exhaustiveness of this literature review. The lack of tools that can be used directly to evaluate the intrinsic relevance of studies in terms of economic analysis and evaluation of misuse led to the development of an assessment chart tailored to our issue and applicable in the French hospital setting. Selected criteria and their assessment may not be useable for assessing the quality of health economic studies in different settings, but it does provide a basis for further studies.
Definition of the perspective? Yes +0. 25 No 0 /0. 25 2. Cost measurement Role of the cost analysis related to the objective? Primary +2 Secondary +1 /2 Definition of measured costs * ? Poor +0. 5 Average +1 Good + 2 /2 Well-established source of cost data? Yes +0. 5 No 0 /0. 5 Method for cost calculation? Yes +1 No 0 /1 Economic data? Measured +1 Estimated +0. 5 /1 Performance of a full economic evaluation  † ? Yes + 1 No 0 /1 3. Measurement of the identified misuse Clear explanation of the inadequacy evaluation? Yes +1 No 0 /1 Use of the Defined Daily Dose (DDD)  ‡ ? Yes +0. 25 No 0 /0. 25 4. Feasibility of the study** Easy +1 Difficult +0. 5 Not feasible 0 /1 Total: /10 ** Feasibility characteristics: Easily feasible = data extracted from a database, non-comparative/interventional study, hospital perspective; Feasible with difficulty = real-world data field, comparative/interventional study, mixed perspective; Not feasible = undefined data source, comparative/interventional study, societal perspective.
Cell viability from the absorbance values was calculated using the following Equation  4 : 𝐿𝐿𝐶𝐶𝐶𝐶𝐶𝐶 𝑣𝑣𝑣𝑣𝜅𝜅𝑣𝑣𝑣𝑣𝐶𝐶𝑣𝑣𝑣𝑣𝑣𝑣 (%) = 𝐴𝐴𝐴𝐴𝑠𝑠 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝐴𝐴𝐴𝐴𝑠𝑠 𝑢𝑢𝑢𝑢𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 × 100 (4) IC50 values were determined using the CompuSyn software.
D The antiproliferative activity of free and encapsulated PTM into Loaded F was assessed using the MTT assay. Lung (A549) and human breast cancer (MDA-MB-231) cell lines were selected based on their sensitivity to PTM  24, 40. The viability of A549 and MDA-MB-231 was monitored after incubation with different concentrations of free PTM and PTM-loaded NPs for 72 h. Blank H were used as controls to evaluate the biocompatibility of the nanocarrier. As shown in Table  7 , the use of Loaded F was associated with a better activity than free PTM both on lung (IC50 = 0. 21 ± 0. 08 µM vs 1. 2 ± 0. 8 µM) and breast cancer cells (IC50 = 2. 2 ± 1. 8 µM vs 4. 6 ± 3. 7 µM). Blank I showed very low toxicity (IC50 > 40 µM) highlighting the biocompatibility of the nanocarrier. These data confirmed that PTM activity in vitro was improved when the drug was incorporated inside nanoparticles.
Acknowledgements Authors are thankful to  Geraldine Agusti ,  Sébastien Urbaniak  from  University of Lyon 1, CNRS, LAGEPP UMR 5007 , for their kind help with TEM images and lyophilization studies. We would like to acknowledge the contribution of  Pierre-Yves Dugas (University of Lyon 1 ,  C2P2 UMR 5265 ) for cryo-TEM observations at the  "Centre Technologique des Microstructures" (CTμ -University of Lyon 1 ). Emeline Perrial  and  Zineb Bousfiha  from  CRCL , are gratefully acknowledged for cell culture.
Characteristics of NO release by irradiation of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF 6 ). The search for alternative NO· donors led to the study of a new complex trans(NO, OH)-[RuFT(Cl)(OH)NO](PF 6 ). The complex is synthesized from previously described 18 trans(Cl, Cl)-[RuFTCl 2 NO](PF 6 ) in water (ESI). Single crystals, suitable for X-ray determination, were obtained from diffusion of diethyl ether in acetonitrile solution of complexes (ESI). The structure of the cationic complex is shown on Fig. 1. The data are in agreement with the well-known {RuNO}  6  Enemark configuration  14  described here as [Ru II (NO) + ]. The NO photo-release is demonstrated by using EPR spectroscopy, since spin trapping combined with EPR spectroscopy is considered as one of the best methods for the direct detection of NO· radicals  21.
Electron paramagnetic resonance experiments (EPR) were performed on a Brucker ESP 500E spectrometer. The following setting was employed for Synthesis. trans(Cl, Cl)-and cis(Cl, Cl)-[RuFTCl 2 NO](PF 6 ) were synthesised as previously reported  18, 19   Crystallographic data. Data were collected at low temperature (100(2) K) on a Bruker Kappa Apex II diffractometer equipped with a 30 W air-cooled microfocus, using MoKα radiation (λ = 0. 71073 Å), and an Oxford Cryosystems Cryostream cooler device. Phi-and omega-scans were used for data collection. The structure was solved by intrinsic phasing method (SHELXT)  33. All non-hydrogen atoms were refined anisotropically by means of least-squares procedures on F² with the aid of the program SHELXL  34. All the hydrogen atoms were refined isotropically at calculated positions using a riding model.
CCDC 1853344 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic data center. NO calibration. The quantitative determination of NO production was performed with a commercial NO detector (ami-NO 700) from Innovative Instruments Inc. Calibration of the electrode in the range of 50-1000 nM was performed by generating NO according to the following reaction: + + → + + - + - • 2 NO 4H 2I 2NO I 2H O 2 2 2 For each calibration, aliquots (80 μL) of aqueous NaNO 2 (∼100 μM) were added to 20 mL of a 0. 03 mol. L -1 solution of KI in 0. 1 mol. L -1 H 2 SO 4. Chronoamperograms were registered at a fixed temperature (25 °C) while stirring the solution in order to maintain a constant rate of oxidation of the produced NO at the electrode surface.
The light intensity was determined by using ferrioxalate actinometer. The sample solutions were placed in a quartz cuvette of 1 cm path -length stirred continuously. The temperature was maintained at 25 °C during the whole experiment. Quantum yield measurements: Light intensities were determined before each photolysis experiments by chemical actinometry procedure. The light intensity was determined by using ferrioxalate actinometer. The quantum yield (φ A ) was determined by the program Sa3. 3 written by D. Lavabre and V. Pimienta  35   λ Abs Tot , the total absorbance; I 0 , the incident intensity measured at 365 nm. The equation was fitted with the experimental data = λ f t Abs ( ) Tot and 2 parameters φ A and ε B (ε B is the molar extinction coefficient measured at the end of the reaction).
λ obs was chosen because it corresponds to a large difference between molar extinction coefficient at the initial and final time of the photochemical reaction. Simulation and optimization procedures were performed by using numerical integration and a non-linear minimization algorithm for the fitting of the model to the experimental data  35, 36. The conditions for the quantum yield determination for trans(NO, OH)-[RuFT(Cl)(OH)NO](PF 6 ) complex in aqueous solution at 25 °C are gathered in Table  S5  (ESI). Moreover, evidence for the inert photolysis product during the experiments has been systematically checked. Cell culture. Vegetative Staphylococcus epidermidis strains (ATCC 35984 and ATCC 12228) were cultivated in LB broth (Sigma-Aldrich, France) at 37 °C under agitation at 200 rpm. Their growth was monitored by optical density (OD) measurements at 600 nm.
Interviews and data collection This study was carried out between January and June 2014. In Mali, traditional healers are organized into associations and were approached by the presidents of these associations with the help of the Department of Traditional Medicine (DMT) in Bamako and of the Malian Federation of  Tradipraticians and Herbalists (FeMaTH). The presidents of these associations introduced the traditional healers who are highly esteemed within their community. Traditional healers were selected in order to avoid family relationship and to have as many women as possible, since they are very few in the profession. A large panel of official traditional healers between 30 and 89 years old were interviewed. Data collection was performed in French or in Bambara. During these interviews, 27 women and 81 men were questioned individually.
Data related to pain conditions such as stomach ache, headache, back pain, ulcer, rheumatism, menstrual pain, nerve pain (including sciatica or pain due to nerve damage), pain due to various diseases such as malaria, diabetes, sickle cell disease and external pain referring to pains due to a shock, an accident or any pain that can be treated topically were collected using a semi-structured questionnaire. Information about local names, plant parts used, ailments, methods of preparation and administration were collected. During the field surveys, whenever a plant species was mentioned the traditional healer was encouraged to show the plant, if possible, in which case the plant was photographed. Plant species were then identified by their local names and their photographs with the help of plant taxonomists from the DMT, Bamako.
Direct compression with RetaLac Appropriate amounts of propranolol HCl and RetaLac were blended in a Turbula mixer (T2C; Bachofen, Basle, Switzerland) at 38 rpm for 5 min. The drug content was varied between 0 and 60 % (Table  1 ). Magnesium stearate was added and the blend was further mixed in the Turbula mixer at 38 rpm for 5 min. Cylindrical tablets were prepared with an instrumented single-punch tableting machine (Frogerais OA, Paris, France) using flat-faced punches  (11. 3 mm in diameter) and the LilTab software (University of Lille, Lille, France). The weight (300 mg) and hardness of the tablets (60-70 N, Tablet Tester 8M; Dr. Schleuniger Pharmatron, Solothurm, Switzerland) were kept constant, unless otherwise stated. The resulting tablet height was 2. 5 mm. The tablet dimensions were measured using a micrometer gauge (Digimatic Micrometer; Mitutoyo, Tokyo, Japan).
Characterization of the powders, granules and blends thereof The particle size distributions of RetaLac and physical HPMC:lactose blends were determined using a laser diffractometer (300RF lens, Mastersizer S; Malvern, Worcestershire, UK). The particle size distribution of the granules (consisting of drug, HPMC and lactose, prepared by wet granulation) was determined via a sieve analysis ("3D"; Retsch, Haan, Germany). The morphology of the particles in RetaLac, physical HPMC:lactose 50:50 blends and of the granules (consisting of drug, HPMC and lactose, prepared by wet granulation) was studied by optical microscopy and scanning electron microscopy (SEM). In the first case, an optical image analysis system ("SMZ-U"; Nikon, Tokyo, Japan), equipped with an AxioCam ICc1 camera (Axiovision Software; Carl Zeiss MicroImaging, Jena, Germany), was applied.
The volumes after 10 and 500 taps (V10 and V500) were recorded (n = 3, mean values +/-standard deviation are reported). The compactability (ability to form tablets) of the lubricated powder blends /granules was evaluated using an instrumented single-punch press (Frogerais OA; LilTab software), equipped with 11. 3 mm diameter flat-faced punches. The following parameters were recorded: (i) force measured at the upper punch, (ii) force measured at the lower punch, (iii) ejection force, and (iv) residual force.
9): RetaLac -177 µm, physical HPMC:lactose blend (50:50) - 189 µm] as well as to differences in the shape and surface morphology of the particles/granules (Figure  3 ). In practice, good flowability is crucial for efficient die filling and high production speeds. Furthermore, the tapped volumes V10 and V500 were determined for the different lubricated powder/granule blends, using the apparatus described in the Eur. Pharm. 7. 0 (2. 9. 34. -3). Figure  1b  shows the results (V10 -V500) obtained for the lubricated: (i) propranolol HCl:RetaLac blends, and (ii) blends of propranolol HCl with physical HPMC:lactose mixtures. The values for lubricated granules obtained by wet granulation loaded with 0 and 10 % drug were around 10 to 11 mL (data not shown; again, please note that these values need to be seen with caution).
In addition, the hardness of the tablets was determined using a crushing force tester. As it can be seen in Figure  4 , satisfying tablet hardnesses were obtained even at low compression forces in the case of RetaLac and the physical HPMC:lactose mixtures. There was no noteworthy difference between these formulations. In contrast, tablets prepared with granules obtained by wet granulation showed much lower hardness values (data not shown). This indicates limited cohesion between the granules. Also, granule fragmentation during compression likely created fine particles, which further decrease the cohesion of tablets and, thus, their hardness. Again, please note that granule optimization was beyond the scope of this study. In all cases, the addition of 10 % propranolol HCl did not substantially affect the "hardness vs.
Results HBsAg in solution. HBsAg, prepared in phosphate buffered saline solution (PBS, 10 mM Na 2 HP0 4 ), (Fig. 1a ) at different pHs, was characterized by small angle X-ray scattering (SAXS) which provides information on the distribution of particles up to ~40 nm in diameter. By analysing the data, provided in Sup. Fig. 1 , with the Inverse Fourier Transform (IFT) method  28  pair distance distributions (PDD) for the HBsAg particle showed a stable morphology for all pH environments (Sup. Fig. 1 ). From the PDD results the particle shape was modelled as an unclosed sphere with a diameter of (32 ± 4) nm (Fig. 1c ), which is too large to enter the 10 nm mesopores of SBA-15. The results were obtained by five DAMMIN runs which were averaged using the DAMAVER software ATSAS package  29. Furthermore, the radius of gyration R G as a function of pH was calculated (Fig.
1b ), and a minimum at pH 7. 4 was observed. Therefore it was concluded that this value is the optimal pH for avoiding protein aggregation before encapsulation. In a second step, to analyse if these samples contained larger aggregates dynamic light scattering (DLS) was performed. The DLS results weighted by the number of particles (Sup. Fig. 2 ) showed that the hydrodynamic diameter of HBsAg was ~30 nm in the measured pH range. This value is consistent with the hydrodynamic diameter (30 ± 3) nm calculated from the shape model obtained from the SAXS data, using the software package HydroPro  30. Additionally, Fig. 1d  depicts the HBsAg diameter distribution by volume, also obtained from the DLS analysis using the NNLS method  31. Aggregates with diameters larger than 200 nm are formed for all pH values, Fig.
To probe the spatial distribution of the salt solution X-ray attenuation tomography was performed using the same pixel size of 6. 37 μm as for the neutron measurements. This allowed us to align the images for direct comparison. Figure  2d  shows a X-ray tomogram of the same part of the sample shown in (c), high attenuation is observed at the same positions and with similar structures in both datasets. Thus from these results we conclude that HBsAg and PBS form large agglomerates within the grains of SBA-15, and that the agglomerated HBsAg is not uniformly distributed. On the other hand, the control samples, i. e. PBS incorporated into SBA-15 without antigen, only showed small agglomeration with drastically different morphology (Sup. Fig. 3 ), than the branching out HBsAg agglomerations 3D visualised in Fig.
2e , for the sample SBA-15 1:2. Consequently we can argue that HBsAg tends to form large agglomerations. After setting a pixel threshold value for the agglomeration, the tomography images were used to analyse the most efficient HBsAg to SBA-15 mass ratio. Figure  2f  shows the relative agglomeration normalised to the amount of encapsulated HBsAg for different HBsAg to SBA-15 mass ratios with constant PBS value. A minimum is observed for the ratio HBsAg:SBA-15 1:40, in good agreement with previous data  7. For this ratio we observe that the amount of agglomeration is indistinguishable from the control sample, i. e. containing only salt. Therefore only a small amount of the encapsulated HBsAg is clustering in the immunological inactive agglomerations. While neutron and X-ray attenuation tomography revealed the morphology and non-uniform distribution of HBsAg agglomeration on the size scale of the SBA-15 grains, X-ray phase contrast tomography with a spatial resolution of 100 nm was requried to obtain 3D information on the SBA-15 particle level (~20 μm, sketched in Fig.
Structural alterations of the HBsAg antigen in solution, previous to encapsulation, were analysed using SAXS and DLS. Ab initio modelling of the SAXS data of HBsAg protein in solution resulted in a half sphere with a diameter of 32 nm, confirming that the antigen is too large to enter the 10 nm mesopores of SBA-15 and therefore must be protected in the macropores. These results suggest that SBA-15 also could be promising as an oral delivery vehicle for other large agents. Through DLS we showed that 3-10% of the HBsAg volume in solution formed larger aggregates. Furthermore, these measurements revealed that the protein is very stable when the sample pH is varied. Interestingly, it was observed that HBsAg at pH 7. 4, the condition used for encapsulation, is indeed the optimal value for avoiding formation of undesired aggregates.
Acknowledgements This research is under the scope of the International Patents  WO07/030901 ,  IN 248654 ,  ZA 2008/02277 ,  KR 1089400 ,  MX 297263, HK 1124791 ,  JP 5091863 ,  CN 101287491B ,  CA 2621373 ,  US 8642258 B2 ,  EP 1942934 B1  and  PI 0503817-0. We would like to thank  Dr. E. N. TenÃsrio  and  D. C. A. de Oliveira  from the  Hepatitis Laboratory of Butantan Institute  for preparing the antigen used in this study. C. L. P. Oliveira ,  M. C. A. Fantini  and O. A. Sant' Anna are CNPq fellows. M. K. Rasmussen  and  H. N. Bordallo  acknowledge the the support for neutron and X-ray research given by Danscatt by the  Danish Agency for Science, Technology and Innovation. We thank  HZB  for the allocation of neutron radiation beamtime. Experiments performed on beamline ID16B were financially supported by the  European Synchrotron Radiation Facility (ESRF), Grenoble, France.