dataesr/scientific-paragraphs-categorization huggingface dataset:
Particle size and shape distributions of isolated crystals were analyzed using the Malvern Morphologi G3. The dry powder was dispersed using compressed air under low energy conditions to avoid particle breakage. Some filters were applied to the raw data to remove artefacts such as dust and fibers. Particles under 55 pixels, with a convexity value less than 0. 80 or with a solidity value less than 0. 65 were removed from the distribution. Circle Equivalent (CE) Diameter measurements were used to compare particle sizes across data sets, and aspect ratio measurements were used to compare particle shapes. Aspect ratio (A) is defined here as the ratio of width (shortest edge, w) to length (longest edge, l); Equation  (9)  gives a dimensionless value between 0 to 1, where 1 equates to an equant shape.
Crystallization Conditions Paracetamol is a well-studied model system; as such, a range of solvents have been used to facilitate crystallization. At the outset of this work, 2-propanol was chosen, as it is reported to produce un-agglomerated crystals of stable polymorphic Form I  [28]. To enable the design of small-scale crystallization experiments in this work, the temperaturedependent solubility of paracetamol in 2-propanol at high temperatures was investigated using turbidity measurements. As seen in Figure  2a , a shallow relationship was found where the solubility doubles roughly every 50 °C. The data is in good agreement with literature values at lower temperatures using gravimetric techniques, although the van 't Hoff extrapolation results in slightly higher solubilities below room temperature in our case  [26].
UV/Visible spectrophotometer The UV absorbance spectra of (R)-CE3F4 were acquired using a Lambda 25 UV/VIS spectrometer from PerkinElmer (Waltham, MA, USA). The acquisition was performed with the software (UV WinLab from PerkinElmer) in scan mode from 195 to 400 nm with an acquisition rate of 480 nm/min, a slit width of 1 nm, and a data interval of 1 nm. Samples were analysed in a quartz cuvette (Hellma Analytics, Paris, France), and the optical pathlength was 10 mm. Appropriate dilutions of (R)-CE3F4 in ACN were performed to obtain 4. 0, 8. 0, and 16. 0 µg/mL. After subtraction of the blank (ACN), absorbances at each wavelength have been divided by the corresponding concentration of the analysed sample to obtain the molar extinction coefficient. Second derivate UV spectra were calculated using the Savitzky-Golay (SG) algorithm to identify UV maxima.
Source heating temperature was set to 300 • C, capillary and tube lens voltage to a value of 35 V and 90 V respectively. Mass/charge (m/z) range was 50-500. Full MS scans were recorded in profile mode using the highresolution FTMS analyzer (R = 60,000). MS/MS fragmentation was performed by collision-induced dissociation (CID) using a normalized CID energy of 35. Data acquisition was controlled by Xcalibur software (Thermo-Fischer Scientific, Les Ulis, France).
Evaluation of (R)-CE3F4 ex vivo stability in human or murine plasma 2. 8. 1. (R)-CE3F4 behaviour in plasma at 37 • C The stability of (R)-CE3F4 in human and murine plasmas was investigated ex vivo for 24 h at 37 • C. Due to the poor solubility in water media, (R)-CE3F4 was first solubilized into DMSO to obtain a stock solution at 10 mg/mL. 3. 6 µL of the (R)-CE3F4 solution was mixed to µL plasma in microcentrifuge tubes to obtain a concentration near µg/mL. Microcentrifuge tubes were put in a rotary agitator at 37 • C. Sampling was achieved at the following times (t = 5 ′ , 15 ′ , 30 ′ , 45 ′ , 60 ′ , 90 ′ , 120 ′ , 180 ′ , 20 h and 24 h). To follow the stability of the (R)-CE3F4 over time, a normalization of the data was made by the ratio between the concentration measured at each sampling time and the concentration measured at 5 min ([CE3F4] t /[CE3F4] 5min = relative concentration (%) at time t).
Data Analysis and Statistics In-house Capture ELISA for Follow-Up of Johnin-Induced IFN-γ Response Corrected OD values (cOD) were calculated by correcting the mean OD values of the samples from stimulation assays tested on one ELISA plate for the mean OD of the negative ELISA control. IFN-γ responses were expressed by the sample to positive ratio (S/P), which was calculated by dividing the cOD of each sample by the cOD of the positive ELISA control.
BOVIGAM Test System for Antigen Testing First, cOD values were calculated as described above. For all antigens that were tested in two concentrations, it was necessary to determine which concentration to use in further data analysis. Therefore, the linear correlation (Pearson's correlation coefficient r) between the cOD values of both antigen concentrations was calculated. If r was higher than 0. 5 and the statistical significance level P < 0. 0001, only one concentration of antigen (10 µg/mL) was selected (Supplementary Table  1 ). IGRA response is presented as the difference between the cOD of antigen stimulated samples and the cOD of the unstimulated sample of the same animal on the same day [S-N].
MAP was re-isolated from feces of 2/8 goats at 1 dpi and from all goats 3-6 and 7-10 wpi. Afterwards, fecal shedding of MAP was observed regularly in 3 goats and intermittently in the other 5 goats until the end of the experiment (for semiquantitative data see Supplementary Table  2 ). Infection was confirmed at the end of the trial by re-isolation of the bacterial strain used for inoculation from tissues of the gastrointestinal tract (GIT) and/or by lesions characteristic for mycobacterial infections. Re-isolation of bacteria from the GIT was not possible from three of the MAH inoculated goats, but characteristic gross and histopathologic lesions were present and mycobacteria were demonstrated in the lesions by IHC, except for two MAH and two MAP-inoculated animals (Table  2 ). Indications of MAP or MAH infection were not found in any of the goats of the control group during the course of the study.
Source of antigen: a Prionics; b CVI-WUR Central Veterinary Institute-Wageningen University & Research, Lelystad, The Netherlands; c WdT Wirtschaftsgenossenschaft deutscher Tierärzte eG, Garbsen, Germany; d APHA Animal and Plant Health Agency, Addlestone, United Kingdom; e IP Institute Pasteur, Paris, France; f MRI Moredun Research Institute, Penicuik, United Kingdom. Gene annotation (GenBank AE016958) according to Li et al. (37) and putative function sourced from KEGG (38).
Osteoarthritis andCartilage Sphk1 deletion in myeloid cells, which reduced cartilage lesions without affecting the synovium. The prevention of lesions in the whole joints with sphingomab might be related to the direct neutralization of a ubiquitous source of S1P, the reduction of local concentration of S1P and the subsequent binding to receptors, whereas JTE013 is restricted to inhibiting S1P 2. This observation addresses the human relevance towards osteoarthritic patients. Sphingomab has been developed as a humanized biotherapy and tested in phase two trial in a renal cell carcinoma setting (NCT01762033). No effect on progression-free survival was observed and was not further developed to the phase 3. There was however a favorable safety profile  57, 58. Our data provide insights in OA conditions that will allow repurposing the drug.
Curcumin has never been clinically subjected for melanoma treatment. However, the compound is currently under phase 1 of clinical trials (NCT03980509) for invasive breast cancer primary tumors treatment. Although the results are still not available, already completed clinical trial (NCT03211104) has proven that orally administered curcumin decreased the PSA levels among patients with prostate cancer  [30]. In the past, both PDT and ECT underwent clinical trials. Calcium electroporation has been successfully used for treatment of cutaneous metastases of melanoma in double blinded randomized controlled phase 2 trial (NCT03628417)  [31]. Currently, ECT with Pembrolizumab for superficial and visceral melanoma metastases treatment is being examined in second phase of clinical trials (NCT03448666).
Mass spectrometry (MS) studies MS experiments were performed on a Compact™ mass spectrometer (Bruker Daltonics, Bremen, Germany) equipped with a standard ESI source. The instrument was operated in the negative-ion mode and calibrated with the Na Formate Clusters in the HPC Calibration Mode. Spectra were recorded for samples dissolved in H2O. Analyte solutions (200 μl) were introduced at a flow rate of 180 μl/h. The instrument parameters were as follows: scan range: 80-1300 m/z, drying gas: nitrogen, flow rate: 4. 0 L/min, temperature: 180 °C and potential between the spray needle and the orifice: 4. 5 kV. For MS spectra analysis, a Bruker Compass DataAnalysis 4. 2 software was used. The experiments were performed in replicates and the mass spectrum with the most prominent signals from the curcumin degradation products was presented in the paper.
Molecular dynamics simulations The experiments of curcumin localization with respect to membrane model involved the insertion of curcumin inside and outside the membrane and observation of the most stable position in which it localizes in the course of simulation. The molecular dynamics simulations were performed with GROMACS 2018. 3 software  [34]  on the calculational cluster in the Department of Theoretical Chemistry and Physics at the Lorraine University. The models for simulations were built with CHARMM-GUI web software and visually inspected with VMD software. The simulated systems were composed of a model of the membrane and curcumin or curcumin degradation products. Simulated molecules were: vanillin, feruloylmethane, ferulic acid and acetone. The chosen molecules were grouped by the degradation reaction pathways from the curcumin reactivity studies  [16]   [17].
The membrane was composed of 64 lipids (70% POPC, 30% Cholesterol) per membrane layer. Before the simulation, the system was solvated in physiological conditions of NaCl water (TIP3) solution. The parameters for small compounds were obtained from CGenFF internet software. The simulation proceeded with the CHARMM36 force field. The systems were minimized, equilibrated (100 ns, NPT conditions: Nose-Hoover thermostat and Berendsen barostat) and simulated for 10 ns to inspect the localization of the examined compounds with respect to the membrane.
Plan-Apochromat 20× (Olympus) objective was used to capture the images. At least 4 samples were analyzed and over 6 cells were used for curcumin content quantification of each sample. Fluorescence intensity was quantified with Fiji package of ImageJ 1. 52p software (ROI Manager, Multi Measure)  [35]  and the statistical analysis (ANOVA) was performed with GraphPad Prism version 8. 0. 0 for Windows, GraphPad Software (San Diego, California USA). The differences between the fluorescence of the samples were plotted on the graphs.
In the next step, cells were washed in PBS, centrifugated and resuspended in 0. 5 mL of PBS. Flow cytometry analysis was performed using a Cube 6 flow cytometer (Sysmex, Warsaw, Poland). The fluorescence of PI was excited with 488 nm laser and assessed with the FL-3 detector (700/50). Data was collected and analyzed by CyView software (Sysmex, Warsaw, Poland).
Acknowledgments: The study was supported by  Statutory Subsidy Funds of the Department of Molecular and Cellular Biology no. SUB. D260. 20. 009  and the light microscopy experiments were partially performed in the  Screening Laboratory of Biological Activity Test  and  Collection of Biological Material, Faculty of Pharmacy  and the  Division of Laboratory Diagnostics, Wroclaw Medical University , supported by the  ERDF  Project within the  Innovation Economy Operational Programme   POIG. 02. 01. 00-14-122/09.
It was therefore necessary to carry out additional experiments to evaluate the influence of the route and time of administration of DTPA on decorporation efficacy for Am. In this work, treatment regimens were especially designed to evaluate whether and to what extent DTPA can chelate Am at the wound site, in blood and/or in tissues as well as the importance of treatment time after wound contamination. For over ten years the laboratory has generated biodistribution data after wound contamination with Am nitrate combined with different DTPA treatment regimens. In all cases, urinary excretion and tissue retention were measured. These biodistribution data obtained with numerous experimental conditions required a systematic approach for the statistical analysis and in particular to account for inter animal variability.
To facilitate the overall analysis of these large biodistribution datasets the statistical tool STATBIODIS was developed in the laboratory  (Lamart et al. 2017 , Lamart et al. 2019). It enables manipulation of a large set of individual data, adjustment of urinary excretion with sum of exponential terms, and comparison of data that accounts for small sample sizes, longitudinal data and mixed effects. STATBIODIS was used previously to analyse biodistribution data of Am obtained after wound contamination with Am nitrate, deposited alone or with Pu nitrate, or with MOX, with presence of Am as a decay product of 241 Pu  (Lamart et al. 2019). In this work, biodistribution data from wound experiments with Am have been collated and analysed to evaluate and compare the efficacy of various DTPA treatment regimens.
Individual biodistribution data Individual tissue retention and urinary excretion data were collated from experiments carried out to evaluate the efficacy of different DTPA treatment protocols after wound contamination with Am nitrate. Available data were obtained from experiments carried out over a period of eight years (Table  1 ). All experiments were in compliance with the European and French regulations for animal experimentation (European directive 2010/63/EU, September 22, 2010 and French decree 2013-118, February 1, 2013) and were approved by the local animal ethics committee. Male Sprague Dawley rats weighing 300-500 g were used for all experiments. Wound contamination was carried out under deep anesthesia (sodium pentobarbital 50 mg/kg, i. p. ) after incision of the left hind leg and a deposit of an Am nitrate solution with an activity of approximately 5 kBq in 50 µL (AmNO3; 99.
In some cases and generally for low activities, urine samples were wet ashed and treated as described above. Bone retention was obtained by multiplying femur activity by a factor of 20  (Griffiths et al. 2012). Uncertainties have been evaluated at 30% (k=2) for samples measured by liquid scintillation counting from the mineralisation step onwards and at 20% for gamma-spectrometry. The retention and excretion data were obtained from multiple experimental steps -from the preparation of the contamination solution to the activity measurement in biological samples. Thus the variability observed between the data may be explained in part by the resulting overall uncertainties inherent in the measurements. To evaluate different decorporation protocols, diethylenetriaminepentaacetic acid (DTPA) was injected intravenously into the tail vein or locally at the wound site, at a dose of 30 µmol/kg, which corresponds to the maximal dose used in man, and at three times after contamination 30 min, 2 h or 1 day (Table  1 ).
Formatting treatment data and selecting data for the analysis The standard format used to organize and archive the raw data in STATBIODOS was extended from the original in order to incorporate treatment data  (Lamart et al. 2017). For groups of rats that received DTPA treatment, two additional tables saved in CSV files (CSV: Comma Separated Values) were created to code for treatment parameters. The first one included treatment drug, route, frequency and dose, e. g. , DTPA, local, single, 30 µmol/kg, respectively. The second one contained treatment times in days. All data related to Table  1  were therefore organized according to this updated format. Individual raw data from each rat were processed using STATBIODIS for computation of new variables, individual data visualization and descriptive analysis.
For example, tissue retention and urinary excretion data were calculated as percent of the administered activity for use in the subsequent steps of the analysis. As the number of experiments has increased in STATBIODIS, a function was developed to select the individual data from the whole database based on experimental characteristics. This function reads the whole database and selects the matching data corresponding to the characteristics specified for the selection, e. g. , element (Am), physico-chemical form (Nitrate), time of euthanasia (1 or 7 days). Additional characteristics can be easily added for a particular selection.
Evaluation, quantification of treatment efficacy and comparison of DTPA treatment protocols from analysis of individual biodistribution data The efficacy of DTPA treatment was evaluated and quantified for Am urinary excretion and tissue retention by comparing data between untreated and treated groups of rats. An i. v. injection of DTPA administered 2 h after wound contamination was used as reference. When a significative effect of treatment was obtained, the DTPA treatment efficacy was quantified for each treated rat as the urinary excretion enhancement factor and as the inhibition percentage of tissue retention (Equation 1 and Equation  2 , respectively): 𝐸𝑛ℎ𝑎𝑛𝑐𝑒𝑚𝑒𝑛𝑡 𝑖 𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) = 𝐸𝑥𝑐𝑟𝑒𝑡𝑖𝑜𝑛 𝑖 𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) 𝐸𝑥𝑐𝑟𝑒𝑡𝑖𝑜𝑛 𝑀𝐸𝐷𝐼𝐴𝑁 𝑢𝑛𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) Equation 1 Where    () is the 24 h urinary excretion at time t of the treated rat  and    () is the median value for the untreated group.
𝐼𝑛ℎ𝑖𝑏𝑖𝑡𝑖𝑜𝑛 𝑖 𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) = 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 𝑖 𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) -𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 𝑀𝐸𝐷𝐼𝐴𝑁 𝑢𝑛𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) 𝑅𝑒𝑡𝑒𝑛𝑡𝑖𝑜𝑛 𝑀𝐸𝐷𝐼𝐴𝑁 𝑢𝑛𝑡𝑟𝑒𝑎𝑡𝑒𝑑 (𝑡) × 100 Equation 2 Where    () is the tissue retention at time t of the treated rat  and    () the median value for the untreated group. Several R functions were developed to automate the computation of the urinary enhancement factor and inhibition percentage of tissue retention for each treated rat and at each time point. To evaluate the influence of DTPA treatment on the relative systemic tissue distribution, ratios of activity between tissues with the highest Am retained activities were calculated and compared (skeleton to liver, kidney to liver and kidney to skeleton). To compare the efficacy of the different DTPA treatment protocols, the effect of treatment time and route were evaluated separately, using data obtained after treatment at 30 min, 2 h or 1 day; and after i.
Comparison tests Prior to running comparison tests, data and effects of interest were identified and characterized in terms of sample size, paired or unpaired data, fixed or random effects. Non parametric rank-based methods adapted to small and uneven samples, independent or paired data, and mixed effects were applied  (Lamart et al. 2019). Overall effects were evaluated using f1. LD. f1 function from the {nparLD} R package  (Noguchi et al. 2012). When the outcome was significant, pair comparisons were carried out using the Wilcoxon test. The Wilcoxon. test function from R provides a p-value and a pseudo-median difference between independent data  (Bauer 1972). The Bonferroni or Holm correction was applied to the obtained p-values depending on sample size. Significant levels of 0. 05 and 0.
Urinary excretion function To quantify the variation of urinary excretion kinetics with treatment, urinary excretion data were adjusted with a sum of exponential terms for untreated and treated rats, respectively, and according to Equation 3. Fitted curves were obtained using a non-linear regression accounting for the time after contamination as a longitudinal variable and the rat as a random variable. The R function nlmer of the {lme4} R package was applied in STATBIODIS with (restricted) maximum likelihood  (Bates et al. 2015). 𝑓(𝑡) = ∑ 𝑎 𝑖 𝑒 -𝑟 𝑖 𝑡 𝑛 𝑖=1 Equation 3 With t the time in days and   (% of administered activity) and   (/day) the regression coefficients.
Therefore the animal was considered as a random variable. Data obtained from untreated and treated rats were independent and treatment corresponded to a fixed effect (Table  2 ). As urinary Am excretion was measured repeatedly for each animal from one to seven days the data obtained over time formed paired (or longitudinal) data. The overall effects on 24 h urinary Am excretion were evaluated statistically accounting for rats as a random variable, i. e. , the effect of treatment with all times considered, the effect of time after contamination regardless of treatment, and the effect of the interaction between treatment and time (Table  2 ). All effects were found to be significant. In particular, the effect of the interaction between treatment and time indicated that the effect of treatment depended on the time after contamination.
Am retention in tissues • Is there an effect of the DTPA treatment, on which tissue and at what time after contamination? After wound contamination with Am, a fraction is transferred to blood and subsequently to systemic tissues with a possible uptake and retention of the actinide. The administration of DTPA 2 h after contamination may remove activity from wound and so prevent deposition in tissues. The individual tissue retention data obtained at day 1 and 7 were compared between untreated rats and rats treated with an i. v. injection of DTPA 2 h after wound contamination with Am nitrate (Figure  3  and Supplemental Table  1 ). Treated groups belonged to single experiments with times of euthanasia at 1 and 7 days respectively, and presented less variability than for untreated groups. Systemic tissues are discussed first.
The current approach could be improved by accounting for the animal and the experiment both as random variables, and/or by applying the pointwise comparison method carried out by Mezaguer and colleagues using the gls function of the {nlme} R package  (Mezaguer-Lekouaghet et al. 2019). Most importantly, the development and use of STATBIODIS fulfils the application of the 3 Rs rule (Replacement, Reduction and Refinement) of the ethical principles in animal research, in radiation toxicology  (Griffiths et al. 2020 ). The efficacy of an i. v. DTPA injection administered at 2 h after wound contamination with Am nitrate was evaluated and quantified based on individual daily urinary Am excretion and tissue retention of Am. Where a significant effect of DTPA was observed, three complementary methods were used to quantify treatment efficacy: (i) the pseudo-median difference between untreated and treated groups, expressed as percentage of activity or activity ratio, (ii) the urinary enhancement factor or inhibition percentage of tissue retention, and (iii) the adjustement of urinary profiles for untreated and treated groups.
The representation of wound retention for each rat in this work illustrated the interindividual variations that may be obtained from wound measurements, whereas experimental conditions were as controlled as possible. The large spread of the results indicated that wound monitoring carried out for workers should also be evaluated and with caution. In addition to measurements, it is crucial to follow-up the 24 h urinary Am excretion for worker monitoring after wound contamination. Despite the observed variability in wound counts, one day after contamination, there was 30%-50% of Am activity remaining at wound site for untreated rats, which is consistent with the strong retention category proposed by the NCRP  (NCRP 2006). Data used by NCRP were obtained using i. m. contamination in rats mostly, whereas data from this paper were obtained for an actual wound contamination with breach of vascular integrity.
ACKNOWLEDGMENTS Results presented here were obtained in the frame of the Orano-CEA collaboration agreement. The authors wish to thank for their assistance  Jean-Claude Wilk ,  Daniel Renault ,  Patrick Pochard ,  Karine Devilliers  (wound contamination experiments and animal care),  Léna Provost  (sample preparation and measurements),  Bruno Redon  and  David Laurent  (Facility safety officers),  Fabrice Huet  (radiation protection and waste management),  Solveig Bibard  ( MSc student ) and  Sophie Dubois  from AnaStats (statistical analysis, https://www. anastats. fr).