dataesr/scientific-paragraphs-categorization huggingface dataset:
2% over the same period analyzed in 2021. 4, 5 From 2021 to February 2022, the number of deaths was 224 in Brazil. 4, 5 Despite several drugs has been explored in clinical trials, there is still no specific therapy for the treatment of dengue. However, in 2015 it was registered the first dengue vaccine termed Dengvaxia (CYD-TDV) produced by Sanofi Pasteur, but its efficiency is questioned due to possible instability, depending on DENV serotype, baseline serostatus and age of the patient. 6 Currently, other dengue vaccines are undergoing in ClinicalTrials. gov. 7, 8 ngue infection can be asymptomatic or manifested with a self-limiting dengue fever (DF), both usually resulting in complete recovery; however, in some cases, the infection evolves to severe dengue (SD), including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).
| Phosphorylated Smad-2 protein labeling The cultures were fixed in 4% paraformaldehyde at 4°C for 20 min and permeabilized with 0. 1% Triton X-100 diluted in PBS for 5 min, After washings, the cultures were incubated with 10 μg/ml DAPI (Sigma-Aldrich) for cell nucleus visualization. The coverslips were mounted in 2. 5% DABCO (Sigma-Aldrich) to prevent loss of fluorescence and examined immediately using a Nikon microscope coupled with image acquisition systems (Nikon Eclipse Ci). Images were quantified using CellProfiler image analysis software (http://www. cellprofiler. org).
ACKNOWLEDGMENTS The authors would like to thank  Dr. Solange Lisboa de Castro  for the critical reading of this manuscript and  Dr. Gisela Freitas Trindade  of  Instituto de Tecnologia em Imunobiológicos, BioManguinhos-Fiocruz  for providing the virus sample. We also thank  FIOCRUZ Platform  where was carried out the RT-qPCR assays. This work was supported by  Instituto Oswaldo Cruz ,  Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Videos were recorded at 420 fps for experiments in which latency to swim initiation was studied. Additionally, 30 fps videos were recorded in experiments where the swimming trajectory was analysed. The angle of the tail was measured before swimming (at rest). Using the ImageJ software (NIH), we determined the tail angle based on the deviation of the tail from a straight line running from the front of the tadpole's head (gray dot; Figure  1F ) through the beginning of the tail (red dot; Figure  1F ) to the most caudal tip of the tail (gray dot; Figure  1F ). A short poke with a fine (rabbit) hair was manually delivered to the tadpole's trunk skin on the left side of its body to initiate swimming (Figure  1G ). Each animal was allowed recovery time of 2 minutes between trials. Latency videos were analysed using the ImageJ software.
The latency (ms) to swim initiation was calculated based on the number of video frames from trunk skin stimulation (time 0 ms on Figure  1H ) to the first head bend (time 129 ms on Figure  1H ). The direction of head movement was also recorded as either on the ipsilateral or contralateral side in relation to the stimulus (ipsilateral to the stimulus on Figure  1H ). FastTrack Software, an open-source tracking software  (Gallois and Candelier, 2021) , was used to detect and track the tadpole in experiments on swimming trajectory (Figure  1I ). A text file containing the X-Y position of the tadpole's body across frames was generated and kinematic analysis was preformed using MS Excel. The following equation was used to calculate the displacement: !(𝑋 ! -𝑋 " ) # + (𝑌 ! -𝑌 " ) # whereby, X0 and Y0 is the starting position of the tadpole and n is the position of the tadpole in the frame under analysis (schematic illustration shown in Figure  1J ).
Recently, identification of an intrinsic lateralized behavior in zebrafish larvae showed that the left/right motor bias is dependent on neurons in the diencephalon that project to the habenula  (Horstick et al. , 2020). The rest of the lesions utilized here caused minor changes to the ratio of contralateral vs ipsilateral starts, thus sustaining the contralateral motor bias. Overall, these data highlight that even at this early stage of development, the midbrain can modulate the side and latency of swim initiation in response to trunk skin stimulation, which makes it essential to the timely and efficient initiation of this behavioral motor response. The significant changes in latency to swim initiation following MHB lesions were further investigated in experiments of fictive swimming in hatchling tadpoles.
6 s). A novel tracking software, FastTrack Software, was used to detect and trace the tadpole's body using an automatic tracking algorithm. (J) Schematic showing the path taken (black), the distance (blue) and the displacement (green). Here, the displacement is described as the shortest distance from the starting position to the next frame (position), with frame intervals indicated as F1, F2 and F3, with F4 representing the final displacement. The distance here is described as the measure of the path taken from the starting to the final position. Abbreviations: Ctrl, control; MHB, midbrain-hindbrain border; ML, midbrain midline; Ipsi MHB + ML, left/ipsilateral midbrain-hindbrain border and midbrain midline; Contra MHB + ML, right/contralateral midbrain-hindbrain border, and midbrain midline.
4% (14/33 trials), synchrony 18. 2% (6/33 trials). (F) Latencies (ms) to the first VR burst after suprathreshold electrical stimulus delivered to the trunk skin of control (orange) and MHB-lesioned animals (violet). Solid circles represent latencies to ipsilateral first VR burst, open circles represent latencies to contralateral first VR burst, and crosses represent VR bursts recorded simultaneously on both sides of the body. Mann-Whitney test for the ctrl group, p<0. 0001: ipsilateral 107. 9, 97. 0-120. 3 ms, contralateral 25. 5, 23. 9-32. 7 ms; Kruskal-Wallis test for  MHB group, p=0. 2108: ipsilateral 36. 5, 23. 3-53. 2 ms, contralateral 43. 6, 24. 8-95. 7 ms, synchrony 25. 8, 12. 7-36. 1 ms. All data are reported as median, 25-75 percentile. Ctrl: n= 5 tadpoles, trials=27; MHB-lesioned: n = 7, trials=33).
Study population and design As a joint initiative of the European Rare Kidney Disease Network (ERKNet), the European Society for Pediatric Nephrology (ESPN), and the PodoNet Consortium, in collaboration with the Chinese Children Genetic Kidney Disease Database (CCGKDD), the German Network for Mitochondrial Disorders (mitoNET), the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE) Clinical Research Network, and the Asian Society for Pediatric Nephrology, we assembled a global cohort of 251 patients affected by primary CoQ 10 deficiency due to biallelic (likely) pathogenic variants in COQ2, COQ6, or COQ8B (see the study by Drovandi et al. 17  for further details of data collection). In this study, we analyzed a subset of 116 individuals who received CoQ 10 supplementation for treatment efficacy and safety.
Changes in proteinuria and estimated glomerular filtration rate (eGFR), the general clinical condition, and neurologic signs and symptoms on treatment were assessed. Changes in proteinuria and eGFR from the pretreatment baseline were recorded at 3 and 6 months and subsequently every 6 months. The general clinical condition and neurologic signs c l i n i c a l i n v e s t i g a t i o n S Drovandi et al. : CoQ 10 supplementation in primary CoQ 10 deficiency and symptoms at any time point during treatment were compared with the status before treatment start. Fifteen patients with missing baseline data for proteinuria or eGFR, 48 patients with ESKD at start of treatment (17 transplanted), 2 patients with temporarily interrupted therapy, and 4 patients with baseline proteinuria in the normal range were excluded from the analysis of change in proteinuria and annual eGFR loss.
Analysis of neurologic status and general clinical condition Data on extrarenal manifestations, especially neurologic disease, and general clinical condition were collected. Neurologic disease modification during CoQ 10 treatment was defined on the basis of the available clinical descriptions provided by the reporting centers. In the COQ6 group, hearing impairment was specifically investigated. The general clinical status was analyzed on the basis of physical performance, feeding ability, growth and weight gain, and the frequency of hospitalization.
ACKNOWLEDGMENTS Programme (EURenOmics; grant  2012-305608 ) and the  German Research Foundation  ( Scha 477/11-1 ). We would also like to thank  Drs. Kei Murayama  and  Masaru Shimura  from  Chiba Children's Hospital, Chiba, Japan , for their contribution to the clinical assessment and follow-up of 2 families. Last but not least, we gratefully acknowledge the help of  Elena Levtchenko  in rolling out the survey.
Study Design The current study is a randomized, controlled, crossover trial in YA and OA men (Figure  1 ). The trial was approved by the Ethical Committee of Personal Protection Ile de France IV (protocol code: 2017-A02879-44) and legal authorities and was registered at www. clinicaltrials. gov (NCT03500003). All study visits were conducted at the Human Nutrition Research Center of Auvergne (CRNH-A; Clermont-Ferrand, France) according to French law, between July 2018 and March 2019. All procedures were carried out in accordance with the guidelines laid down in the Declaration of Helsinki. A 3-week run-in period was conducted before a crossover intervention consisting in the acute and single ingestion of a milk or yogurt serving. During the run-in period, the participants were requested to do not consume dairy foods and to limit the consumption of fermented non-dairy as described by  Kim et al.
Targeted and Untargeted GC-MS Using an internal GC-MS database, 14 metabolites were targeted in this study and additionally identified using retention indices (RI) (see Table  1 ). An additional 3 metabolites with significant differences were identified in the untargeted mode. Using the NIST database, two of these were identified at level 3 (octadecenoic acid and octadecadienoic acid). However, because the position of the double bonds, as well as the cis/trans isomerism could not be determined, these metabolites could not be identified at level 1. Preparation of the serum samples and their measurement by GC-MS followed the method described previously by Trimigno et al. (17). Briefly, a two-step derivatization, consisting of methoximation and silylation, was applied to 100 µL of serum sample and the samples were analyzed on a GC-MS 7890B/MS5977A (Agilent Technologies, Santa Clara, CA, USA) with a CombiPAL autosampler (CTC-Analytics AG, Zwingen, Switzerland) and a DB-5 ms fused silica capillary column (60 m, 0.
Statistical Analyses Non-parametric robust statistical tests were used in this study due to many variables not showing a normal distribution. Descriptive analysis, including median with interquartile range (IQR), was performed for all variables. All data was processed in the R environment (4. 0. 3). Baseline differences between the age groups were assessed for all parameters by comparing the samples at time point 0 of the YA and OA groups by Wilcoxon signed-rank test. A P-value < 0. 05 was considered statistically significant. To identify features derived from the untargeted LC-MS and targeted GC-MS that presented a significant postprandial time response (at least one time point) after intake of either milk or yogurt, nonparametric analysis of longitudinal data with ld. f1 function was used (nparLD R package, P < 0.
0. 12) (29) after the normalization to the maximum value of each feature. The postprandial-responding variables were then tested using the f1. ld. f1 function of the nparLD package (Wald Chi-Squared test, P < 0. 05) to investigate the effect of age, product, and their interaction during the 6 h period following the intake of the dairy products. Features were considered as significant after Benjamini-Hochberg  (30). FDR correction for the untargeted LC-MS dataset (P < 0. 05 and FDR <0. 1) and without FDR correction for the targeted GC-MS dataset (P < 0. 05). The features showing significant differences in age, product, and/or an interaction effect, were further evaluated with a Wilcoxon signed-rank test to identify which of them responding differently after milk and yogurt intake in the YA and OA groups separately (paired, P < 0.
Identification of Discriminant Features Discriminating features derived from the untargeted metabolomics LC-MS analyses were subjected to identification as described in Pimentel et al. (19). Shortly, the Human Metabolome Database  (31)  and the National Institute of TABLE 1 | List of identified discriminant blood metabolites derived from LC-MS and GC-MS analyses with significant differences in their iAUC, C max (C min ), or t max (t min ) [median (IQR)] either by age, product, or their interaction after the intake of milk or yogurt in young and older men.
05; d comparison the fasting level of metabolites between before and after the run-in period, ↑: significantly increased during the run-in period, ↓: significantly decreased during the run-in period, P < 0. 05; e comparison between the fasting levels of baseline at postprandial challenge (0 h) and after 24 h (24 h) by Wilcoxon signed-rank test, ↑: significantly increased 24 h after the intake of dairy, ↓: significantly decreased 24 h after intake of dairy Standards and Technology database (NIST v14) were used to identify the features. The following two orthogonal criteria were used to consider a level 1 identification of the metabolites: (i) mass accuracy: ∓ 5 ppm; (ii) retention time of feature in sample compared to retention time of pure standard: ∓ 10%  (32, 33). A targeted approach was used for the identification of 17 discriminant features from GC-MS, using an in-house reference compound library, retention indices (RI), and spectral data as described in Münger et al.
Kinetic Variables Calculation The postprandial metabolomic features that showed significant postprandial responses (see Figure  3 , clusters 1 and 7) were selected for kinetic analyses. The maximum concentration (C max ) and the time to reach C max (t max ) were analyzed by noncompartment methods using the ncappc package implemented in R (v 4. 0. 3. ) (34). The minimum concentration (C min ) and time to reach C min (t min ) were calculated in case of metabolites that showed negative postprandial responses.
Background: Current standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496). Methods: In the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/mL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy.
Many CT therapies and IS therapies are also associated with significant toxicity and side effects, and have variable clinical efficacy  (2). Therefore additional therapeutic options for HES, including OCS sparing treatments, are needed. Mepolizumab is a humanised monoclonal antibody that binds to and inactivates interleukin (IL)-5, thereby reducing eosinophil haematopoiesis and survival  (7, 8). By doing so, mepolizumab is able to reduce blood eosinophil counts to within normal physiological limits  (9). Mepolizumab is an approved add-on therapy for a number of eosinophilic diseases, including severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis (EGPA) and HES in multiple regions worldwide  (10, 11). The double-blind, Phase III 200622 study (NCT02836496), demonstrated that mepolizumab significantly reduced the incidence of disease flares, fatigue severity and blood eosinophil counts versus placebo in patients with HES, with a favourable safety profile  (9).
Study Design and Patients This was a post hoc analysis of data from the 200622 study (NCT02836496), a randomised, placebo-controlled, doubleblind, parallel-group, multicentre, Phase III trial, full details of which have been reported previously  (9). Briefly, patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks in addition to their existing HES therapy. Patients were ≥12 years of age at screening; had a diagnosis of HES ≥6 months before screening based on organ system involvement and/or dysfunction that could be directly related to a blood eosinophil count >1500 cells/mL on ≥2 occasions, and/or tissue eosinophilia, without a discernible secondary cause; were receiving stable HES therapy for ≥4 weeks before the baseline visit; had ≥2 flares within the past 12 months and a baseline blood eosinophil count ≥1000 cells/mL at screening.
In the 20-week open label extension of the 200622 study (205203/NCT03306043) a ≥50% reduction in OCS daily dose was achieved by 28% of patients using OCS during the first 4 weeks of the study  (21). Mepolizumab may therefore offer the additional benefit of OCS reduction for patients requiring chronic or repeated courses of OCS. The limitations of the parent 200622 study have been previously reported  (9). The post hoc nature of the current study led to additional limitations. Owing to the rarity of HES, the numbers of patients in some of the baseline treatment subgroups were small, with 23 patients receiving IS/CT (± OCS), 60 receiving OCS No IS/CT and 25 receiving No OCS/IS/CT. Whilst the 200622 study was powered to detect an absolute reduction of 38% in the proportion of patients experiencing a flare with a sample size of 50 in each arm, this post hoc analysis was not powered for such testing.
Statistical testing or more detailed analysis of between group differences was therefore not attempted. As such, the results of the subgroup analyses presented here should be viewed as indicative rather than definitive and further studies will be needed to fully explore the factors contributing to the patterns seen. In addition, as historical treatment data were not collected, it was not possible to investigate prior treatment use and the rationale for the treatments patients were receiving at baseline. This circumstance, together with the heterogeneous nature of HES also limits the ability to draw conclusions on any differences in disease severity between baseline therapy groups, and limits the interpretation of the results. Despite these caveats our results provide additional insights, beyond the primary results of the 200622 study  (9) , into the treatment benefits of mepolizumab for patients with HES receiving varying baseline therapies.
Data Our work is based on the public data provided by the ATLAS 3D  (Cappellari et al. 2011a)   2  and MATLAS  (Duc et al. 2015; Bílek et al. 2020)   3  surveys. The ATLAS 3D survey targets nearby (<42 Mpc) massive (M K < -21. 5 mag) ETGs (galaxies lacking spiral arms) and is volume complete. The survey strives to collect all possible information about its targets. All of the data we used in this paper was taken from ATLAS 3D , except for those on the photometric irregularities (tidal features, irregular outer isophotes) and dust lanes; that information was taken from the catalog of  Bílek et al. (2020)  extracted from the MATLAS survey. The MATLAS survey took very deep (∼28. 5 mag arcsec -2 ) wide-field (1 × 1 • ) optical (the u * , g , r , and i bands) images of all ATLAS 3D ETGs, except for those in the Virgo Cluster, with the 3.
6 m Canada-France-Hawaii Telescope, employing observing and data processing strategies optimized for detecting largescale low-surface-brightness structures. We used the MATLAS sample  (Bílek et al. 2020)  where we excluded the two galaxies without mass measurement (PGC 056772 and PGC 061468). In total, the sample considered here contains 175 objects. The list is available in electronic form at the CDS. Importantly, the MAT-LAS survey avoided the cluster environments, and therefore our results pertain only to galaxies in low-to medium-density environments such as galaxy groups. In this paper, we characterize the mass of a galaxy by M JAM , adopted from  Cappellari et al. (2013). It is defined as M JAM = (M/L) e L, where L is the total luminosity of the galaxy and (M/L) e is the effective dynamical mass-to-light ratio of the galaxy within the galactocentric distance of one R e derived using Jeans Anisotropic Modeling  (Cappellari 2008).
We exploited multilinear regressions on data from the ATLAS 3D and MATLAS surveys in order to study the correlations of various parameters that are expected to be sensitive to mergers with the rotational support for galaxies of a fixed mass and environmental density. The results were then interpreted making use of the facts that every merger indicator has a different lifetime and is sensitive to a different type of merger (minor or major, wet or dry). It was crucial to study the correlations at a fixed mass and environmental density in order to account for the so-called confounding effect, that is, the fact that λ N R e correlates with the galaxy mass and with the environmental density, and that different mergersensitive parameters correlate with these quantities as well. We also considered other observational results from the literature, mostly from observations of the high-redshift Universe.
We assume that the Australian fires have no impact in the northern hemisphere. The spectral variability of the aerosol extinction is represented using the measured monthly mean Ångström exponent from SAGE III/ISS, for January to April 2020. The merged OMPS/SAGE dataset for the aerosol spectral extinction is further discussed in Sects. 2. 2-2. 3. The interaction of the radiation fields with the pyrogenic aerosols depends also on other optical properties of these particles that are not directly accessible from observations. In particular, the absorption and scattering properties of the aerosol layer must be represented in the radiative transfer modelling. Thus, different hypotheses have been considered for these non-measured optical parameters of fire aerosols. The absorptivity of the layer is modelled by means of the single scattering albedo (SSA), which is varied, in our calculations, from 0.
The dailyaverage shortwave TOA RF for the fire-perturbed aerosol layer is calculated as the SZA-averaged upward diffuse irradiance for the background simulation minus that with the Australian fire aerosol perturbation, integrated over the whole shortwave spectral range. The shortwave surface RF is calculated as the SZA-average downward global (direct plus diffuse) irradiance with aerosols minus the background, integrated over the whole spectral range. We estimate equinox-equivalent daily average RF by assuming that the duration of day and night is equal. Building upon the v1. 0 and v1. 5 versions, an up-to-date v2. 0 version of the aerosol extinction profile inversion algorithm has been recently developed  (Taha et al. , 2020). With respect to previous datasets versions, OMPS-LP aerosol extinction profile scheme v2.
0 exhibits significant retrieval improvements, especially in the Southern Hemisphere (SH), when compared with independent datasets  (Taha et al. , 2020). This is very relevant for the present study which focuses on a purely southernhemispheric event. Thus, as main input data to our offline RF estimates, the OMPS-LP v2. 0 aerosol extinction observations at 675 nm have been used. An older OMPS-LP data collection (OMPS-LP USask,  Zawada et al. , 2018)  was used in K20.