dataesr/scientific-paragraphs-categorization huggingface dataset:
The VVS-SAS registry and population The VVS-SAS registry was initiated by collaborating experts (Study Director: Professor Vincent Puel) to standardise routine care and data collection for this population in participating centres in France. The registry includes all consecutive adult patients (thus avoiding selection bias) simultaneously suffering from recurrent, idiopathic VVS (or orthostatic intolerance) and obstructive sleep apnoea. Within the framework of this protocol, VVS or orthostatic intolerance is diagnosed by cardiologists with VVS expertise (most often as a function of a is determined by a patient's report for the time period covering months -6 to D0. The number of episodes of (pre)syncope occurring after SAS management is determined by prospectively recording (pre)syncope events during the study and counting them for the time period covered by months +6 to +12 (S after ).
Visits The information collected during this study corresponds to routine practice in the participating centres. Recruitment and follow-up take place during regularly scheduled, yearly visits for patients consulting for idiopathic recurrent syncope. Following patient information and verification of eligibility criteria, the patient is enrolled in the VVS-SAS registry and data collection then starts. Table  2  lists the assessments that are performed at the first baseline visit, as well as a subset of the latter that are reperformed on a yearly basis. Each assessment is described in the following paragraphs, along with which data are recorded. Data are recorded for all yearly visits that occur during the inclusion period and then for a subsequent 12-month follow-up period. The inclusion period is not set in an a priori fashion; inclusions will proceed until 60 patients are included.
Baseline data collection The following baseline characteristics will be recorded once at the start of the study: age, sex and socioprofessional category (agricultural, entrepreneur, senior professional, intermediate professions, employee, worker, retiree, no activity). The presence/absence of facial dysmorphia variables will be recorded (retrognathia, archival palate, mallampati score 3 or 4, anterior open bite, cervico-mental angle blunting, other otorhinolaryngology abnormalities (lower tongue, tonsillar hypertrophy)). The age at which the patient's first syncope/ presyncope occurred will be recorded.
24-hour Holter monitoring Holter monitoring is performed on a yearly basis. Data will be collected for a full 24-hour period for each patient, with separate datasets for heart rhythm data and arterial pressure data. Hearth rhythm data will be centrally analysed under the direction of Professor Frédéric Roche at the University Hospital of Saint-Etienne, Saint-Etienne, France. The data recorded include the total number of heartbeats analysed, and the percentage of successive RR (interbeat intervals between all successive heart beats) intervals that differ by more than 50 m. In addition, the following four variables will be recorded at three time levels (daytime defined as between 07:30 and 21:30, nighttime, and total): (1) the SD of NN (interbeat intervals from which artefacts have been removed) intervals (ms), the root mean square of successive RR interval differences (ms), the SD of successive RR interval differences and the Heart Rate Variability Index.
In terms of fourier transformed frequency domains, the following four variables will be recorded (again for the same three time levels): total power (ms 2 ), very low frequency power (ms 2 ), low frequency power (ms 2 ), high frequency power (ms  2  ). Blood pressure data are recorded every 15 min during a full 24-hour period, with notation of the times at which the patient went to sleep and got up in the morning. Blood pressure data will be analysed under the direction of Professor Philippe Gosse at the University Hospital of Bordeaux, Bordeaux, France. In addition to the number of blood pressure measurements performed, the means and SD for systolic pressures, diastolic pressure and heart rate are recorded for the daytime, nighttime and total time frames.
Analysis strategies General considerations Statistical analyses will be performed under the direction of the study methodologist (NM). The intention-to-treat (ITT) population is defined as all persons included in the VVS-SAS registry. The per-protocol (PP) population is defined as a subset of the ITT population without major protocol deviations and with a satisfactory SAS treatment response (ie, an Apnoea-Hypopnoea Index <10). The threshold for statistical significance is set at a bilateral probability of 0. 05. Prior to database freezing, a detailed statistical analysis plan will be designed. The following paragraphs present the planned general strategies for analysis; any deviations from these strategies must be approved by the study methodologist and documented as such.
Before-after SAS management comparisons Changes in variables before versus after SAS management (including the primary outcome) will be analysed with comparisons of centrality for paired data (paired t-test or paired Wilcoxon signed rank test) at the ITT level. A sensitivity analysis involving the PP population will also be performed. Before-after SAS management comparisons will be further summarised via their unadjusted and confounder-adjusted (see next section) effect sizes (eg, mean differences) accompanied by 95% CIs. Similar methods will also be applied to comparisons between the first and last 6 months of SAS treatment to contrast changes associated with patient adaptation during the early stages of treatment deployment.
ETHICS AND DISSEMINATION The registry was approved by a randomly selected independent ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number Open access CPP/2-18) and the French National Committee on Informatics and Liberties (CNIL reference number 2 164 019 v 0) in accordance with French law. Because the registry simply regroups existing data without changing routine care, the patient is informed about the study and the data are collected unless the patient indicates his/her opposition to the study (as per French law). One publication presenting before-after SAS management comparisons and longitudinal analyses is planned. A second publication presenting further exploratory association results will be published as a post-hoc study. The accompanying datasets will be made available to interested researchers on provision of an appropriate CNILapproved protocol, as per current French regulations.
Code availability. The MAR code used in this study is tagged as v3. 9. 3 on https://gitlab. com/Mar-Group/MARv3. 7. See http://www. mar. cnrs. fr for more information about downloading MAR. Data availability. The present-day MAR simulation is available on http://doi. org/10. 5281/zenodo. 3066734. The future MAR simulations 5 will be made available on https://zenodo. org after acceptance.
However, the lack of comparative studies between conventional coils and deep coils, does not permit to conclude about the safest and the most efficient one. In this context, we conducted a double blind randomized rTMS controlled trial to investigate the therapeutic effectiveness of the Magventure cool D-B80 coil (DC coil), applied daily during an acute phase of 4 weeks in TRD. Patients suffering a TRD were recruited between October 2015 and March 2018 from the Department of Psychiatry at Sainte Marguerite University Hospital, in Marseille, France. This study was approved by the institutional Ethics Committee, and registered at ClinicalTrials. gov (NCT02559466). Inclusion criteria were participants over the age of 18 who met the DSM-5 criteria of major depressive episode and treatment resistant criteria (failure of two successive trials of antidepressants at an adequate dose for six weeks each).
Data and sample Quantitative data come from the Mexican Family Life Survey (MxFLS, 2002-2012). This was the first longitudinal survey with a representative sample of the Mexican population at national, rural-urban and regional levels. Sampling directives were drawn up by the National Institute of Statistics. The survey covers a 10-year period with three distinct waves. The first wave was carried out in 2002 with 35 677 individuals surveyed in 8440 households (living in 150 municipalities distributed across sixteen Mexican states). Given the longitudinal dimension of the survey, the second (2005-2006) and the third (2009-2012) waves were based on the initial sample in 2002. In both waves, the follow-up rate of the initial sample exceeded 90 % at the household level. MxFLS data include detailed information on socio-economic characteristics of households and individuals.
Anthropometric data were collected for all household members directly at their home by trained staff from the National Institute of Public Health. Waist circumference was measured exactly at navel level using a flexible tape (accuracy of 1 cm), weight with a set of digital scales (accuracy of 0•1 kg) and height with a stadiometer (accuracy of 0•5 cm). The longitudinal dimension of the MxFLS (2002-2012) provides the opportunity to analyse how childhood body weight in 2002 correlates with schooling attainment 10 years later. More specifically, we measured schooling outcomes by the length of schooling (i. e. years of completed primary, secondary and tertiary education in 2012) and by a binary outcome indicator distinguishing individuals who obtained a high-school grade in 2012 (i. e. bachillerato) from individuals who did not obtain this grade.
Discussion Childhood obesity and central adiposity are main concerns for emerging countries where overweight is predominant such as Mexico, Brazil, South Africa and Egypt, by potentially limiting human capital accumulation and future development capacities. The aim was to provide insights about the weight-schooling relationship in the context of such countries. In particular, we focused on the adverse effect of childhood body weight on school attainment using a 10-year long panel data set from Mexico (MxFLS, 2002-2012). To explore the relationship between childhood body weight in 2002 and educational attainment 10 years later, we followed a cohort of adolescents across time and used OLS and PSM estimators. Moreover, we considered general and central body weight measurements based on adjusted BMI (i.
Acknowledgements Acknowledgement: The author thanks  Matthieu Clément  and  Dolores Jiménez-Rubio  for their precious help. Financial support: The study did not beneficiate from a specific financial support. Conflict of interest: The author has no conflict of interest to declare. Authorship: P. L. is the sole author of this article. Ethics of human subject participation: Regarding the use of the  Mexican Family Life Survey , no ethical approval is required. This database is anonymous and does not contain personal information. Please see the website for more details about the data: www. ennvih-mxfls. org. The author is responsible for all remaining errors.
Acknowledgments This study was supported by the  Fonds IMMUNOV, for Innovation in Immunopathology. The study was also supported by the  Institut National de la Santé et de la Recherche Médicale (INSERM) , by a government grant managed by the  Agence National de la Recherche  as part of the " Investment for the Future" program  ( ANR-10-IAHU-01 ), and by a grant from the  Agence National de la Recherche  ( ANRflash Covid19  "AIROCovid" to FRL). J. H. is a recipient of an  Institut Imagine MD-PhD  fellowship program supported by the  Fondation Bettencourt Schueller. L. B. is supported by the  EUR G. E. N. E. (reference # ANR-17-EURE-0013 ) program of the  Université de Paris IdEx  # ANR-18-IDEX-0001  funded by the  French Government  through its " Investments for the Future" program.
, 2020). Clinical trials to test several agents are underway, but existing antivirals have limited efficacy against SARS-CoV-2 and are most efficient in reducing viremia when taken early in infection  (Gonçalves et al. , 2020; Kim et al. , 2020; Goyal et al. , 2020). Prophylactic therapy using (repurposed) antivirals has been proposed  (Jiang et al. , 2020; Pagliano et al. , 2020; Spinelli et al. , 2020) , is currently being tested (US National Library of Medicine, 2020 (accessed November 12, 2020) (e. g. study NCT04497987), and is successfully used in the prevention of HIV infection and malaria  (Mermin et al. , 2006; Baeten et al. , 2012). Monoclonal antibodies, such as REGN-COV2 and Eli Lilly's bamlanivimab, once authorized, could also be used for prophylaxis. These agents could be an essential tool to reduce the probability of SARS-CoV-2 infection in individuals at high risk, e.
Of course, the quantitative predictions, which depend on R 0 , change. Considering the current uncertainty in the basic reproductive number and burst size, we developed an interactive application to compute and visualize the establishment probability and deterministic dynamics as a function of parameters. This application can be used to update our results as our knowledge of intrahost dynamics and treatment efficacies progresses (it can be accessed by following the instructions on github. com/pczuppon/virus_establishment/tree/master/shiny). The critical efficacy above which infection is entirely prevented is the efficacy at which the intrahost basic reproductive number, adjusted to the antiviral drug under consideration, passes below 1. The value of this critical efficacy could readily be obtained in a deterministic model.
Conclusion Clinical trials are underway to test the efficacy of several antiviral drugs  (Harrison, 2020; Li and Clercq, 2020; Fragkou et al. , 2020; Sheahan et al. , 2020; Maisonnasse et al. , 2020) , either as a curative treatment or as a prevention. The efficacy of repurposed drugs is in a 20-70% range  (Gonçalves et al. , 2020) , but better antiviral drugs might be available soon. Thus, our prediction that a drug efficacy needs to be greater than 90% to prevent infection establishment may be within reach in a near future. An interactive tool has been made available to update this prediction with refined parameter estimates that will come from large dataset obtained in the different target populations where prophylaxis may be relevant (such as health care workers or high-risk individuals).
Simulations The individual based simulations are coded in C++ using the standard stochastic simulation algorithm for the reactions described in system (3). Estimates for the establishment probabilities, depicted by dots in the subsequent figures, are averages of 100, 000 independent runs. Establishment was considered successful when the population size of infectious virions was at least 500. Estimates for the time to reach a detectable viral load are obtained from 10, 000 simulations where the sum of infectious and non-infectious virus particles exceeded 2, 000 copies. The code and the data to generate the figures are available at: github. com/pczuppon/virus_ establishment.
Acknowledgments P. C. has received funding from the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Skłodowska-Curie  grant agreement PolyPath  844369. This project was partially funded by the  ANR TheraCov  ( ANR-20-COVI-0018 ) and the  BMGF foundation  under grant agreement  INV-017335. O. T. and F. B. received funding from  Grant Equipe Fondation pour la Recherche Médicale   EQU201903007848. F. B. received funding from the  Centre National de la Recherche Scientifique  ( Momentum grant ). F. D. received funding from the  national research agency (ANR)  through the grant  ANR-19-CE45-0009-01. Portions of this work were done under the auspices of the  US Department of Energy  under Contract  89233218CNA000001  (A. S. P. ). This work was also supported by the  Los Alamos National Laboratory LDRD program  (A.
Proteins were detected on an iBright FL1000 Imager (Invitrogen) by using the ECL method according to the manufacturer's instructions (Fischer Scientific, Illkirch, France). To determine the working range of each antibody, different protein quantities, antibody concentrations, and time of exposure were tested. To calculate the relative density (RD), ImageJ software was used, and the intensity of each protein was normalized to Actin. The data obtained were then expressed as the ratio of the intensity of the protein in treated cells to that of the corresponding protein in untreated cells. The level of protein phosphorylation was expressed as the ratio of the phosphorylated protein versus the total protein.
Statistical Analysis All data were presented as mean ± S. E. M. Data were analyzed using Sigma-Aldrich Stat (version 3. 0, Systat Software, San Jose, CA, USA). One-way ANOVA was used to assess differences among groups followed by Newman-Keuls or Mann-Withney post hoc test. When the 2 groups were compared, differences were assessed by Student's t-test. Differences between groups were considered significant if the P-value was * P < 0. 05, ** P < 0. 01, *** P < 0. 005 versus control or WT mice. # P < 0. 05, ## P < 0. 01, ### P < 0. 005 versus TN or SIRT1 iKO mice.
ISO elicits a catecholaminergic stress which has been well-documented to induce cardiac dysfunction associated with ER stress  [12, 22]. Following ISO challenge, heart rate, FS, and EF were decreased in WT mice, while left ventricular internal diameters and wall thickness were not affected (Figure  4B  and Figure  S3 ). The diminution of heart rate, FS, and EF induced by ISO was more important when SIRT1 was knocked out. Together, these data indicated that SIRT1 protects the heart from TN-and ISO-induced injury. To determine whether the cardioprotective effect of SIRT1 was mediated through the regulation of autophagy in vivo, the level of LC3-II was evaluated in WT and SIRT1 iKO mice after TN or ISO injection. The accumulation of LC3-II promoted by TN or ISO was returned to the basal level in SIRT1 iKO mice (Figure  4C ,D), indicating that SIRT1 is required for autophagy induction in response to TN or ISO.
These results corroborated those obtained in H9c2 cells and adult cardiomyocytes and suggest that SIRT1 protects the heart from ER stress-induced injury by promoting protective autophagy. Cells 2020, 9, 426 11 of 22 and wall thickness were not affected (Figure  4B  and Figure  S3 ). The diminution of heart rate, FS, and EF induced by ISO was more important when SIRT1 was knocked out. Together, these data indicated that SIRT1 protects the heart from TN-and ISO-induced injury. To determine whether the cardioprotective effect of SIRT1 was mediated through the regulation of autophagy in vivo, the level of LC3-II was evaluated in WT and SIRT1 iKO mice after TN or ISO injection. The accumulation of LC3-II promoted by TN or ISO was returned to the basal level in SIRT1 iKO mice (Figure  4C, D ), indicating that SIRT1 is required for autophagy induction in response to TN or ISO.
Funding: This research was funded by the grant  ANR-10-LABX-33  as members of the  Laboratory of Excellence LERMIT ,  FRM  ( Fondation pour la Recherche Médicale)  to  A. Garnier  (# DPM20121125546 ),  Région Ile de France CODDIM  to  R. Ventura-Clapier  (# cod110153 ) and by grant  VEGA 2/0110/15 ,  APVV-15-0302  and  SK-FR-2015-0007  to  M. Novotova. A. Guilbert  received a fellowship from  Région Ile de France CORDDIM.
1A ). At Day 6, Kupffer cells were added to the co-culture since they did not tolerate the embedding process (data not shown) but were able to enter the hydrogel once formed. Several media were tested to maintain viability of the four cell types. The homemade Liver Co-culture optimized media, described in the Materials and Methods section, allowed us to obtain a viable co-culture of four cell types up to Day 10 (Fig. 1B ). To assess the suitability of the model, co-culture viability, cytokine secretion and lipid droplet content were measured from Day 3 to Day 15 on four independent experiments. The human 3D liver co-culture at a basal level displays a good viability from Day 3 to Day 15 as reflected by ATP level measurement (Fig. 2A ). PHH CYP3A4 enzymatic function was evaluated and it remains stable from Day 3 up to Day 13 (Fig.
Human 3D NASH model regulates gene set related to pathways involved in NASH development. To better characterize the human in vitro 3D NASH model, a global gene expression analysis has been performed by RNAseq. For this purpose, three samples from day 3, 8 and 10 healthy 3D cocultures and from day 8 and 10 in vitro 3D NASH model were processed. Global RNA-seq datasets from 3D healthy and NASH models were first interrogated using a Principal Component Analysis (PCA) to cluster these two models during in vitro development (Fig. 7A ). A distinct sample separation is observed between 3D healthy and NASH models (represented by circles and triangle, respectively), highlighting that NASH culture condition alters the overall gene expression pattern of 3D liver co-cultures (Fig. 7A ). A time effect on both healthy and NASH 3D liver model is also visualized, being more noticeable between Days 8 and 10 in the 3D NASH co-culture.
0. 1. 81 (Omicsoft, Qiagen). Briefly, raw data QC was performed then a filtering step was applied to remove reads corresponding to rRNAs as well as reads having low quality score. Mapping and quantification were performed using OSA4 [1C] (Omicsoft Sequence Aligner, version 4)  (Hu et al. , 2012). p-values obtained after one-way ANOVA with random effect followed by comparisons at fixed day. Fold Changes (95% Fold's CI) are obtained with back transformation of the log estimated difference for CXCL10 and with Hodges-Lehmann's estimations for other cytokines were responsible for critical revision of the manuscript and funding acquisition; Marion Duriez and Anne-Céline Le Fèvre were responsible for study supervision, study design, data acquisition analysis and interpretation and drafting the manuscript.
Bioinformatic tools are currently being developed to better understand the Mycobacterium tuberculosis complex (MTBC). Several approaches already exist for the identification of MTBC lineages using classical genotyping methods such as mycobacterial interspersed repetitive units-variable number of tandem DNA repeats and spoligotyping-based families. In the recently released SITVIT2 proprietary database of the Institut Pasteur de la Guadeloupe, a large number of spoligotype families were assigned by either manual curation/expertise or using an in-house algorithm. In this study, we present two complementary data-driven approaches allowing fast and precise family prediction from spoligotyping patterns. The first one is based on data transformation and the use of decision tree classifiers. In contrast, the second one searches for a set of simple rules using binary masks through a specifically designed evolutionary algorithm.
These lineages are known to cause TB in humans throughout the world, and some of them (such as Lineage 3) are relatively specific to certain regions, whereas others (such as Lineage 4) are more globally distributed  (5). In the SITVIT2  (6)  proprietary database of the Institut Pasteur de la Guadeloupe (http://www. pasteurguadeloupe. fr:8081/SITVIT2/), which is an update of previously released SpolDB/SITVIT databases  (7, 8) , Lineage 1 is known as EAI; Lineage 2 is known as Beijing; Lineage 3 is known as Central Asian (CAS); Lineage 4 includes Cameroon, Haarlem (H), Latin-American-Mediterranean (LAM), NEW-1 (formerly named Ural-2), S, T, Turkey, Ural and X; Lineage 5 is known as AFRI 2 and AFRI 3; Lineage 6 is known as AFRI 1 and Lineage 7 is known as Ethiopian. Two newly discovered lineages (Lineage 8 and Lineage 9) seemingly restricted to Africa were recently described  (9, 10).