dataesr/scientific-paragraphs-categorization huggingface dataset:
The platform produces output in a display that the user can consult by clicking on the day or period of interest (Figure  1 ). As discussed in 14, the accuracy of the Epidemic Calculator package has not been extensively tested, and the platform has several shortcomings. Caution is therefore necessary in interpreting the results presented below. The model parameter values employed in this study are presented in Table  1. Estimates of ℛ0 for COVID-19 vary approximately four-fold from c. 1. 5 to 6. 5  (17) (18) (19) (20) , and we adopt a modal value of 2. 5. Although the quantitative model predictions differ for lower and higher values of ℛ0 in the observed range, the qualitative patterns remain the same.
o. i 10:1) cells (Fig. 4b, c, e, f ). Similarly, the complementation of H37Rv with a functional TbD1 locus resulted in a significative reduction of the intracellular growth ability in both cellular models analyzed (Fig. 4b, c, e, f ). Virulence of TbD1 mutants in guinea pigs and C57BL/6 mice. The virulence profiles of TbD1-deleted and complemented mutant strains were then evaluated in aerosol-infected guinea pigs, and compared to the corresponding 79112 and H37Rv WT control strains. Data obtained in the Mtb 79112 background revealed that the deletion of the TbD1 locus conferred an improvement of the in vivo replicative potential, resulting in a 2 log and 1 log increase in CFU values recovered from lungs and spleen, respectively, of animals infected with the mutant strain relative to that obtained in guinea pigs infected with the WT strain (Fig.
Primer walking, PCR and in vitro transposition were used for finishing purposes. The assembled consensus sequences were validated using Illumina reads. A highquality, contiguous genome sequence of 4394 kb in 9 contigs were generated for strain 79112. Remaining gaps estimated not to exceed 2 kb. For Mtb strains Tb36 and Mtb79499 Illumina 36-bp single-end reads were assembled using Velvet  84  and generated contigs were ordered according to similarity with the reference genome of Mtb H37Rv 82. Genome assemblies of Mtb strains 79112, 79499 and Tb36 have been deposited in the EMBL/ENA database under the study accession number PRJEB30653. Sequences will also be made accessible via the MicroScope Magnifying Genome (MaGe) web server  85  , https://www. genoscope. cns. fr/agc/ microscope/home/index.
Fluorescent data were specified for collection at the end of the annealing/elongation step in each cycle. For each gene, a standard curve of amplification was performed using known amount of DNA from H37Rv. Based on the CT values obtained, a linear regression line was plotted using a custom-made software supplied with the Bio-Rad CFX96 Touch Real-Time PCR Detection System instrument, and the resulting equation is used to calculate the efficiency of amplification. To normalize the results between samples, the sigA gene and Mtb H37Rv were used as reference gene and reference strain, respectively. The expression level of each gene was reported as ratio of expression (fold induction) compared to the expression level in different strains, using following calculation: ratio of induction = Efficiency of amplification (gene of interest) -ΔΔCT , where ΔCT = CT(gene of interest) -CT (sigA) in each strain tested, and ΔΔCT = ΔCT(strain tested) -ΔCT(H37Rv).
1 v/v/v. Mycobacterial solution and matrix were mixed directly on the target by pipetting and the mix was dried gently under a stream of air. MALDI-TOF MS analysis was performed on a4800 Proteomics Analyzer (Applied Biosystems) using the reflectron mode. Samples were analyzed by operating at 20 kV in the positive and negative ion mode using an extraction delay time set at 20 ns. Statistical analysis. Data analysis was first performed by using the Bartlett's test and the Levene's test. According to results obtained, analysis of variance (one-way Anova) followed by Bonferroni post hoc test (in vitro survival assays and mouse infection studies) or F-test for heteroscedasticity (guinea-pig virulence studies) were performed. Based on results obtained d with the F-test, the univariate analysis of variance test followed by Sidak post hoc tests was performed.
Acknowledgements We are grateful to  Professor Denis Mitchison , passed away in July 2018 aged 98, who initially enabled this study by kindly providing us with some of his original South Indian Mtb strains. We also thank  Cristina Gutierrez  for sharing selected Mtb clinical isolates,  Dick van Soolingen  for providing Mtb Tb36 strain,  William R. Jacobs  for the gift of vector pYUB412 and  Graham F. Hatfull  for providing vector pJV53. We thank  Fabien Le Chevalier ,  Laleh Majlessi ,  Alexander Pym ,  Paul Wheeler ,  Stephen Gordon  for help and stimulating discussions,  Magali Tichit ,  Sabine Maurin  and  Johan Bedel  from the histology service of the  Institut Pasteur  for their technical support,  Alessandro Massolo  for helpful advice in statistical analyses, and  Jean Jaubert  for help with the setup of the C3HeB/FeJ model.
This work was supported in part by the  French National Research Council ANR  ( ANR-10-LABX-62-IBEID ,  ANR-16-CE35-0009 ,  ANR-16-CE15-0003 ), the  Fondation pour la Recherche Médicale  ( DEQ20130326471  and  SPF20160936136 ) and the  European Union 's  Horizon 2020 Research and Innovation Program  ( 643381 ).
Study design The international, multicenter, randomized, sham controlled RADIANCE-HTN SOLO trial design has been described previously  (1, 2). The study was approved by local ethics committees or institutional review boards and conducted in accordance with the declaration of Helsinki. All participants provided written informed consent to complete up to 3 years follow-up. The procedures followed were in accordance with institutional guidelines. The study is registered at https://www. clinicaltrials. gov (NCT02649426).
We used multiple regression analysis to look at the main determinants of VVV of daytime, home and office SBP, including treatment (RDN or sham), age, sex, BMI, baseline SBP and eGFR. Comparisons between groups at baseline and 12 months were made using unpaired t-tests for continuous variables and Fisher's exact test or chi square, as appropriate, for categorical variables. Continuous variables are expressed as mean ± standard deviation, unless otherwise specified and between-group differences are expressed as mean and corresponding two-sided 95% confidence intervals (CI). All analyses were performed using statistical analysis system (SAS) software version 9. 4 (SAS Institute, Cary, NC, US). A p-value lower than 0. 05 (twosided) was considered significant.
This work was supported by  ReCor Medical Disclosures : MA has received research grants from The  French Ministry of Health ,  Quantum genomics and European H2020 program ; has received grant support and non-financial support from  ReCor Medical  and  Idorsia ; and has received personal fees from  CVRx. JD  has received grant support from  ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Acist Medical, Astra Zeneca, Pie Medical, Medical, Medtronic, CVRx ,  Ablative Solutions ,  Vascular Dynamics ,  ROX Medical  and  Tarilan Laser Technologies  and grants from  Medtronic. FM is supported by  Deutsche Gesellschaft für Kardiologie, Deutsche Hochdruckliga, and Deutsche Forschungsgemeinschaft  ( SFB TRR 219 ), and has received grant support and personal fees from  ReCor Medical ,  Medtronic ,  Berlin Chemie ,  Bayer , and  Boehringer Ingelheim.
Results cRt sequence dataset and phylogenetic tree analysis. To evaluate the selective regime acting on the coding-sequence and protein product of the crt gene, we first retrieved orthologous CRT sequences from public databases. Non-Plasmodium species have not been included in the study because we cannot confirm that PfCRT homologous protein(s) in those organisms are truly orthologous to PfCRT. As we had enough evolutionary information with CRTs from Plasmodium, we choose this smaller dataset to avoid introducing any putative bias in our evolutionary analyses  37. Among the retrieved 24 Plasmodium CRT sequences, only that of the bird-infecting P. relictum appeared incomplete with an absence of twenty amino acid positions in the C-terminal region. The other sequences showed high conservation in length, ranging from 423 to 425 amino acids (Supplementary Table  S1 ), resulting in the presence of few indels (8 amino acid positions) in the CRT multiple sequence alignment that were removed from subsequent analyses (Supplementary Fig.
S1 ). The phylogenetic tree produced from the curated crt sequence alignment was highly congruent with the acknowledged phylogeny of Plasmodium species  38  , with four main monophyletic groups (bird parasites, primate parasites 'Plasmodium' , rodent parasites and primate parasites 'Laverania') supported by high bootstrap values (≥90%; Supplementary Fig. S2 ). Variable levels of conservation across the crt gene sequence and phylogeny. The selective pressures acting on the CRT-coding DNA sequence were searched for by estimating the non-synonymous to synonymous substitution rate ratio ω (=d N /d S ) across lineages (branch model) and codon sites (random-site models) using the codeml program (ω > 1 indicates positive selection whereas ω < 1 reflects purifying selection)  39. The entire crt gene was found to evolve under a variable selective regime across Plasmodium phylogeny as the free-ratio model (that allows ω to vary along branches in the crt phylogenetic tree) had better fit to the data than the one-ratio null model M0 (which supposes only one ω value for all branches; p = 1.
Those extremities contained several sites that were found phosphorylated in PfCRT  40  , including T416 which notwithstanding appeared highly conserved. Altogether, the data indicate that much of the CRT protein has evolved under purifying selection over Plasmodium evolution. Identification of DMT template structures to predict PfCRT tertiary structure by homology modeling. In order to get a finer map of evolutionary constraints in a structural context, we aimed to produce a tertiary structure of PfCRT by homology modeling. By reviewing the literature, we found that, since 2016, several high-resolution 3D structures of DMTs containing 10 TMs have been determined by X-ray diffraction in different conformational states: the nucleotide sugar GDP-mannose transporter Vrg4 resolved in an inward-facing state (PDB ID: 5oge)  36  , the triose-phosphate/phosphate translocator TPT resolved in an occluded state (in complex with 3-phosphoglycerate; PDB ID: 5y79)  32  , and the aromatic amino acids and exogenous toxic exporter YddG (PDB ID: 5i20)  41.
5 Å and 5. 4 Å after exclusion of the loops (Supplementary Table  S5 ). Hence, these results indicated that the structures have a similar fold but a different degree of intra/extracellular gate openness. We also noted that these RMSD values are consistent with those observed for other transporter superfamilies. For example, we retrieved from the Protein Data Bank three members of the Major Facilitator Superfamily (MFS), LacY (PDB ID: 2y5y)  46  , GlpT (PDB ID: 1pw4)  47  and EmrD (PDB ID: 2gfp)  48  which, despite exhibiting low paired sequence identity (~15%), shared a similar fold and arrangement of 12 TMs 48 , with Cɑ-based RMSDs including TMs-connecting loops ranging from 5. 9 Å (LacY-GlpT) to 8. 9 Å (GlpT-EmrD; Supplementary Fig. S5 ). Therefore, we assumed that PfCRT may share a similar fold to the aforementioned 10 TMs-containing DMT proteins, at least regarding the membrane spanning region.
e. with a sequence identity <15%)  50  , and manually optimized it in order to align the conserved amino acid positions identified from the profile-profile alignment (see the final alignments for PfCRT-Vrg4 and PfCRT-TPT in Supplementary Figs. S6 and S7 respectively). After the refinement and minimization steps, we checked the quality of the two built PfCRT models using local stereochemistry (MolProbity). For comparison, we used as controls several high-resolution 3D structures: the two DMT template and the PfCRT cryo-EM structure  35. The two PfCRT models exhibited similar quality indices than these experimentally-determined control structures as suggested by Ramachandran plots (Table  2 ). General (ERRAT  51  , Prosa II  52  ) and transmembrane-specialized (QMEANBrane 53 ) 3D quality metrics also provided high confidence in structure conformation, energies and non-bonded interactions between atoms of the PfCRT OC and PfCRT IF models, when compared to the templates and other highly refined structures including PfCRT cryo-EM from the Protein Data Bank (Table  2  and Supplementary Fig.
After substituting mutant positions in PfCRT cryo-EM (S72, T76, S220, D326 and L356) to WT (C72, K76, A220, N326 and I356) with UCSF Chimera  57  , we noticed that most of drug resistance-associated amino acid sites were similarly oriented in the PfCRT models compared to PfCRT cryo-EM (Fig. 2C ), except a major difference for the amino acid I218 in PfCRT IF. Altogether, the two models we produced were accurate and reliable for subsequent analyses. Vacuolar and tM sites have evolved under strong purifying selection. We used our new PfCRT models to test whether some PfCRT regions, apart from the N-and C-terminal extremities, were differentially conserved. We used the fixed-site models and partitioning function implemented in the codeml program  58. We tested two different partitioning of crt codon sites: 1) cytoplasmic-half versus vacuolar-half sides of the transporter and 2) non-TMs (i.
Materials and Methods collection of pfcRt orthologous sequences. The PfCRT amino acid sequence (PlasmoDB database identifier: PF3D7_0709000) was queried against the specialized Plasmodium database (PlasmoDB, release 38) and the non-redundant protein database of NCBI using blastp and tblastn searches (e-value cutoff = 10 -6 , BLOSUM62 scoring matrix)  65. Twenty four CRT protein and corresponding cDNA sequences from distinct Plasmodium species were retrieved (Supplementary Table  S1 ). For P. ovale spp. and P. inui sequences, exon skipping was manually performed so as to reconstruct the full cDNA and amino acid sequences. Multiple protein and codon sequence alignments. The CRT multiple sequence alignment was first generated with TM-aligner  66  using the transmembrane-specific substitution matrix PHAT  67  and with gap opening and extension penalties set to 10 and 1, respectively.
The output alignment was visually inspected and manually edited using BioEdit v7. 2. 5  68. The positions of the CRT multiple alignment containing gaps in ≥30% of all sequences were removed. Then, a crt nucleotide sequence alignment was generated with PAL2NAL 69 using the cleaned CRT protein sequence alignment as template. phylogenetic analysis. A phylogenetic tree was built from the crt nucleotide sequence alignment by using the maximum likelihood method implemented in PhyML v3. 0  70  , after determining the best-fitting nucleotide substitution model using the Smart Model Selection (SMS) package  71. A general time-reversible model with optimized equilibrium frequencies, gamma distributed among-site rate variation and estimated proportion of invariant sites (GTR + G + I) was used, as selected by the Akaike Information Criterion.
The comparisons of models were performed using Likelihood Ratio Tests (LRTs)  78. For every LRT, twice the log-likelihood difference between alternative and null models (2Δℓ) was compared to critical values from a chi-squared distribution with degrees of freedom equal to the difference in the number of estimated parameters between both models  79. Modeling the pfcRt tertiary structure. When the analyses were performed, no experimental structure was determined for PfCRT. Consequently, we aimed at modeling it in different conformational states using a template-based protein structure modeling approach. The PfCRT sequence was submitted to interactive Phyre2  42  and HHpred 43 servers to find the best available, appropriate templates. The nucleotide sugar GDP-mannose transporter Vrg4 (inward-facing state, PDB ID: 5oge)  36  and the triose-phosphate/phosphate translocator TPT (occluded state, PDB ID: 5y79)  32  were identified as sharing putative similar structural folds with PfCRT with confidence >99%.
Two tyrosines of PfCRT IF (Y68 in TM 1 and Y345 in TM 9) paired with two tyrosines of Vrg4 (Y28 in TM 1 and Y281 in TM 9; Fig. 4A) reported to be essential for the translocation of Quality metrics for PfCRT models and templates. a The experimentally-determined tertiary structures of two DMTs (Vrg4 and TPT) were used as templates for homology modeling of PfCRT structure. PfCRT cryo-EM corresponds to a PfCRT mutant structure recently determined in an inward-facing state by cryo-electron microscopy. PfCRT IF and PfCRT OC correspond to PfCRT wild type models in inward-facing and occluded states, respectively. b ProSA II generates an overall quality score compared with the ones from all experimentally determined protein chains available in the Protein Data Bank. c MolProbity indicates the accuracy of a macromolecular structure model and diagnoses local problems by all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria.
Acknowledgements We are extremely grateful to  I. Callebaut  for her expert guidance and advices for the homology modeling analyses and for her critical review of the manuscript. We thank  B. Offmann  for helpful suggestions regarding the critical evaluation of model validity. We thank  Y-F. Huang  for help with FuncPatch analysis,  R. Coucke  for early work on the project, and  R. Duval  for helpful discussions. R. Coppée is a recipient of a  PhD fellowship  from the doctoral school MTCI n°563. This work was partly supported by the  Agence Nationale de la Recherche  ( ANR-17-CE15-0013-03  to  J. Clain ).
Materials and methods PRO BONO was developed within the Young European Society for Radiotherapy and Oncology (yESTRO) Committee. An online cross-sectional survey was conducted using Survey Monkey (www. surveymonkey. com). Participants (professionals working in the field of radiation oncology), were invited to participate voluntarily (May-October 2018) via (a) email, after identification as members of ESTRO in its database, (b) social media (Facebook/ Twitter) and (c) ESTRO newsletter. The only 2 requirements to be eligible to participate in the survey were to be a radiation oncology professional andmember of ESTRO. For the present study, medical doctors with a degree specialization in radiation and/or clinical oncology were selected. Demographics and professional information useful for stratification were collected.
A stepwise method was used for variable inclusion of potentially confounding and competing predictors. To avoid unnecessary reductions in statistical power, confounding (age, gender and marital status) and competing (alexithymia, empathy, and work-related variables) predictor variables were included in the regression models only if significantly correlated with the outcome variables (p-value < 0. 05). Collinearity was assessed using the statistical factors of tolerance and Variance Inflaction Factor (VIF). All the analyses were performed with the software ''Statistical Package for Social Sciences-version 25" (SPSS-25) (IBM, Armonk, New York).
Study population and design The design and outcome of the RESPOND (Repositionable Lotus Valve System-Post Market Evaluation of Real World Clinical Outcomes) have been previously published. 12 As reported in the prior publication, the protocol was approved by the locally appointed institutional review boards/ethics committees and the study was conducted in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice and the ethical principles outlined in the Declaration of Helsinki. The study was sponsored by Boston Scientific Corporation and registered with ClinicalTrials. gov (NCT#02031302) and all patients gave written informed consent. Patient flow and echocardiogram availability are shown in Figure  1.
Echocardiography acquisition protocol Sites were asked to perform transthoracic echocardiography (TTE) at baseline, discharge and 1-year post-TAVR following a pre-defined independent Core Laboratory (Dr. Soliman, Cardialysis, Rotterdam, The Netherlands) protocol. In brief, the sweep speed of the pulsed-and continuous-wave Doppler signals was set at 50-100 mm/sec. The velocity scale of the color Doppler was optimized for display at ±50-70 cm/s and ≥22 Hz frame rate during the entire study. Focused and zoomed views were recorded when appropriate to ensure a high-resolution display of region on interest such as PVL jets. All echocardiographic data were independently analyzed by an independent core laboratory according to current guidelines. 13, 14.
Statistical analysis Continuous variables are summarized as mean ± standard deviation (SD) or median (interquartile range) and categorical variables as absolute frequencies and percentages. Comparisons of continuous variables were performed using the t test or appropriate non-parametric test (the Wilcoxon test for paired samples and the Mann-Whitney U test for independent samples). Categorical variables were compared using the Chi-squared test. Statistical analysis was performed with SAS 9. 3 (SAS Institute Inc. , Cary, NC, USA). All probability values were two-tailed, and a value of P < 0. 05 was considered significant.
Limitations RESPOND was a multicenter international observational registry aligned with the local standard of care. Due to regional differences in standard of care, the protocol did not mandate the collection of 1-year echocardiograms. TTEs were collected for approximately 65% (550/850) of patients included in the 1-year follow-up. Comparison of patients with or without 1-year echocardiographic data is shown in Supplementary Table  6. However, we have shown, in a relatively large sample of patients that the favorable Lotus THV performance and the low PVL rate persist, and that initially mild PVL improves to trace or no PVL at 1-year after the Lotus THV implantation.
Data Collection The following data were collected for each patient: (1) Socio-demographic data: age, sex, associate medical condition (penicillin allergy, smoking status, consumption of alcohol, diabetes, asthma, psychiatric disorder); (2) Clinical symptoms of severity; (3) Number and type of space involved by the infection; (4) Treatment on admission: ongoing antibiotic (family and duration of treatment) and/or antiinflammatory treatment (corticosteroids or Nonsteroidal anti-inflammatory drugs, NSAIDs); (5) Duration of hospital stay and number of surgeries; (6) Bacteriological results, results of culture and sensitivity, antibiotics adaptation;  (7)  Complications  [10].
Consequently, experts enrolled in any MTB must comprise clinicians, pathologists, bioinformaticians, biologists and geneticists; all participating in interprofessional teamwork. The second feature of any MTB is the ability to understand the rapid evolution of technologies, (e. g. genetic panels, analytical software, knowledge libraries or clinical databases) and biomedical knowledge, as well as continuous therapy development. These aspects alone represent particular challenges for establishing standardized protocols and guidelines that inform the activities of these tumorboards. Publications that share experiences of MTB implementation, very often report their data after one or 2 years of activity; i. e. MTB decisions and activity processes are presented in the form of patient flow diagrams or decision trees, detailing case evaluation work  [6, 22] , which mostly focus on clinical outcomes.