dataesr/scientific-paragraphs-categorization huggingface dataset:
Crystallographic data collection, processing and structure refinement. Diffraction data were collected at the ID14-1 and ID23-1 beamlines of the European Synchrotron Radiation facility (ESRF, Grenoble, France) at 1. 9 and 2. 3 Å resolution, for RXRα and RARβ complexes, respectively. Diffraction data were processed using MOSFLM  [57]  and scaled with SCALA from the CCP4 program suite  [58]. The structure was solved by using the previously reported structures 3E94  [59]  or 4JYI  [37] , for RXRα or RARβ complexes, respectively, from which the ligand was omitted. Initial F o -F c difference maps showed a strong signal for the ligand, which could be fitted accurately into the electron density. The structure was modelled with COOT [60] and refined with REFMAC  [58]  using rigid body refinement, restrained refinement, and individual B-factor refinements.
Funding: This work was supported by the  Agence Nationale pour la Recherche  ( ANR-13-BSV6-000301 ), the  Association pour la Recherche sur le Cancer  ( ARCA08/4/1056 ). It was also supported by funds from the  Institut National de la Santé et de la Recherche Médicale , the  Centre National de la Recherche Scientifique ,  Université de Montpellier.
Results A total of 7317 patients enrolled in the survey between September 2013 and December 2014 met eligibility criteria. The 18-month follow-up data were available in 6118 patients. Figure  1  shows the reasons for excluding patients (3% of patients did not meet the inclusion criteria, 8% of patients did not have baseline data for adherence assessment, and 5% of patients did not have follow-up data). The baseline characteristics are described in Table  1  for the total population, i. e. both patients included in and excluded from the analyses (Table  1 ). For the included patients, the mean age was 62. 8 years with a predominance of male patients (74. 4%). Overall, 82. 7% of patients were in NYHA class II or III and mean LVEF on echocardiography was 33. 1 (10) • Follow-up data missing (n=367) • Baseline data for model fitting missing for BBs, 70.
However, the overall proportion of patients who changed healthcare provider between baseline and the 18-month visit was small (5. 9% patients). QUALIFY centres were selected by national coordinators, on a voluntary basis, and selection bias cannot be excluded. Our score was based on therapies recommended in the international guidelines, which were in use at the time QUALIFY was initiated. 18, 34, 35 Therefore, adherence and clinical outcome data related to neprilysin inhibitor therapy, which is recommended for use in HF in current international guidelines,  5, 6  were not collected. We measured physicians' adherence and not patient compliance or persistence, which means that we were unable to assess the impact of these factors over the long follow-up period of this analysis. The possibility of unmeasured bias, which exists in all observational studies, may have resulted in over-or underestimation of treatment effects.
Funding This work was supported by a research grant from  Servier, France. The funding source had no role in the study design, in the analysis and interpretation of the data, and in the decision to submit the manuscript for publication, but did assist with the setup, data collection, and management of the study in each country. The sponsor funded editorial support for editing and revision of the manuscript and received the manuscript for review before submission. Conflict of interest: M. K. reports personal fees from  AstraZeneca ,  BMS ,  Menarini ,  Novartis ,  Amgen ,  Servier ,  MSD ,  Novo Nordisk  and  Sanofi , outside the submitted work. S. W. reports grants from  Servier Affaires Medicales , during the conduct of the study. L. T. reports personal fees from  Servier , during the.
Diet indices Scores Three dietary scores assessing the overall diet quality were derived from the FFQ data at all three phases: The Alternate Healthy Eating Index of 2010 (AHEI-2010)  [21]  is based on 11 components, six components for which the highest intakes are considered to be ideal (vegetables, fruits, whole grains, nuts and legumes, long chain omega-3 fats (DHA and EPA) and polyunsaturated fatty acids), one component for which moderate intake was supposed to be ideal (alcohol), and four components for which avoidance or lowest intake are considered to be ideal (sugar-sweetened drinks and fruit juice, red and processed meat, trans fat, and sodium). Each component is given a minimal score of 0 and a maximal score of 10, with intermediate values scored proportionally. All the component scores are summed to obtain a total AHEI-2010 score, which ranges from 0 to 110, with a higher score representing a healthier diet.
Covariates assessed in 2002/2004 Three types of covariates were considered, socio-demographic factors, health behaviours and health status factors and were derived from the questionnaires completed by the participants and from measures assessed during the physical examination in 2002/2004 (measures of systolic and diastolic blood pressures, weight, height, fasting glucose and HDL-cholesterol assessed from fasting blood samples taken from participants). Socio-demographic data consisted of sex, age, ethnicity (White/South Asian/Black), marital status (married or cohabiting vs. single/divorced/widowed), and socioeconomic status (SES) based on occupational position, categorized into three groups: high (administrative), intermediate (professional or executive) and low (clerical or support)  [15].
Nuclear Magnetic Resonance Nuclear magnetic resonance (NMR) spectra were recorded with an Avance III Bruker NMR spectrometer operating at 600 MHz for 1 H and 150 MHz for 13 C. The chemical shifts are given in δ (ppm) and coupling constants (J) are reported in hertz (Hz). The one-(1D) and two-dimensional (2D) spectra were processed using Topspin. The NMR spectra were measured as solutions in chloroform-d or methanol-d following the solubility of the compounds in 5 mm outer diameter tubes. The structural identifications of the compounds were achieved by comparing their spectroscopic data ( 1 H, 13 C-NMR) with the values found in the literature.
Digital image processing The stereo correlation set-up requires a pair of low noise, temporally stable cameras that are rigidly mounted in relation to each other during system calibration and subsequent data capture. The cameras used for these tests were GO-5000-USB from JAI's Go Series with objective KOWA LM12HC where lenses are 12. 5 mm. The frame rate was 50 Hz. Cameras were placed in order to look at the lateral and anterior sides of the thigh to obtain the needed field of view. Care was taken to match cameras centres. After cameras' setting, calibration was carried out using a calibration grid adapted to the size of the field of view. Data were processed with VIC-3D software. Motion analysis and stereo correlation acquisitions were synchronized using a common trigger box sending a rising edge square signal to both systems.
Population The population from whom samples have been evaluated and described in this work is the highest risk cohort of seronegative solid organ transplant patients who were enroled in the Phase II randomised and double-blinded placebo controlled cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant trial and received organs from seropositive individuals, described elsewhere  [15]. In the original study this cohort represents 11 vaccine recipients and 5 placebo, however, for this study removal of consent for future studies and a patient death mean the data presented is from the remaining 10 vaccine and 4 placebo recipients. No other selection criteria were applied. In short, the vaccine or placebo was given in three doses: at day 0 (baseline), 1 month and 6 months later. Following vaccination, blood samples from patients were obtained consecutively.
Neutralizing antibody responses were detected in sera from seronegative vaccine recipients in the post-transplant period The data thus far argued for a vaccine dependant boost in gB antibody levels post challenge with HCMV (i. e. post-transplant). The key question, however, was whether this boost in gB antibody levels may reveal a hitherto undetectable response in the pre-transplant sera that could explain vaccine efficacy. Thus we asked whether the increase in gB IgG levels early post-transplant revealed evidence of neutralizing activity previously undetectable in the pre-transplant sera samples  [16]. Neutralisation was scored by the ability of the sera to prevent lytic infection of fibroblasts when pre-incubated with the virus prior to infection. Experimental conditions were established whereby seronegative pooled patient serum had no impact on virus infectivity whilst the well characterised neutralizing antibody ITC88 showed almost complete neutralization of infection (Fig.
Acknowledgements These studies were funded by The  Rosetree Trust  ( A1601 ) and  Stoneygate Trust  ( JS16/M730 ) and the  Wellcome Trust  ( 204870/Z/16/ Z ). We are also indebted to the support of the  Royal Free Charity. The original clinical trial of gB/MF59 was supported by a grant from the  National Institute of Allergy and Infectious Diseases  ( R01AI051355 ) and  Sanofi Pasteur. Additionally , we like to thank  Sanofi Pasteur  for the gift of the recombinant gB antigen used in the original vaccine. The Funding sources had no role in the study design, data collection, data analysis, data interpretation, writing, or in the decision to submit to publication. The corresponding author had access to all the data and made the final decision to publish.
3D ) or 500 (Fig. 3E ) fungal cells. During infection, and especially in the later stages of disease, the aerated lung volume decreased, while the total volume of the lungs increased (Fig. 3D-E ). Furthermore, we assessed the potential of these imaging techniques to differentiate between the high-and low-inoculum groups. Both BLI and µCT were able to demonstrate a significant difference in the progression between both groups (Fig. 3 ). When compared with additional cross-sectional data at week 3. 5 p. i. , the bioluminescence signal and tissue-lesion volume on µCT was significantly different between both inoculum groups (Fig. S5 ). In contrast, CFU counts could not discriminate between the fungal loads in both inoculum groups. Overall, BLI and µCT data indicate that the development of detectable disease in the low-inoculum group is delayed by approximately 1 week compared to the highinoculum group, while having a similar progression rate.
To further prevent problems of reduced mRNA accumulation deriving from intron-less gene sequences in C. neoformans  (Goebels et al. , 2013) , a 55 base pair (bp) intron sequence deriving from the C. neoformans glyceraldehyde-3-phosphate dehydrogenase gene was introduced at position 70 downstream to the ATG start codon. As this intron causes a frameshift and early termination of translation if not spliced from the transcript, only correctly processed mRNA results in the production of a functional luciferase. To regulate gene expression, the synthetic luciferase gene (here referred to as CnFLuc; GenBank accession number MH920367) was fused by in vitro recombination (InFusion HD cloning kit, Takara/ Clontech) with a 1167 bp EF1a promoter and a 402 bp TRP1 terminator sequence from C. neoformans.
In vitro bioluminescence assay Triplicate 10-fold serial dilutions of the harvested fungal suspension were prepared in a black 96-well plate (Nunc ® Microwell, Thermo Fisher Scientific, Merelbeke, Belgium). An equal volume of D-luciferin solution (final concentration 0. 15 µg/ml in PBS; Luciferin-EF, Promega, USA) was added. Images were acquired using an IVIS Spectrum system (Perkin Elmer, Waltham, USA) with the Living Image software (version 4. 5. 2) and an exposure time of 1 min, F/stop of 1 and medium binning. Individual regions of interest (ROIs) were placed over each well for quantification of the total photon flux. Afterwards, the number of CFUs per well was determined by triplicate plating of serial dilutions on Sabouraud agar, cultured as specified above. For analysis of the emission spectra from bioluminescent C.
Intravenous injection model Animals (n=3) were infected by injection of 50,000 fungal cells in 100 µl of PBS via the tail vein (modified from  Ngamskulrungroj et al. , 2012). Bioluminescence and MR images were acquired on day 3, 5 and 7 after infection, after which animals were sacrificed for ex vivo BLI and CFU counting. Two additional animal groups (n=3 each) were only scanned on day 3 or 5 and sacrificed afterwards to obtain ex vivo BLI data and CFU counts for intermediate time points (cross-sectional study). Animals (n=3) infected with wild-type H99 were only scanned with MRI on day 3, 5 and 7 after infection, after which CFU analysis was performed for one animal.
Quantification of BLI results Living Image software (version 4. 5. 4, Perkin Elmer, Waltham, USA) was used to quantify the total photon flux ( photons/second) in the ROI. For in vivo BLI, the total photon flux in the lung, brain, nose or abdominal region was determined by placing a ROI over these regions with a size of 2. 5×2. 1 cm, 1. 6×1. 3 cm, 0. 85×0. 60 cm or 2. 5×1. 3 cm, respectively (Fig. S7 ). Consecutive frames with an exposure time of 1 min each were acquired for a period of 20 min. For each animal, the frame giving the highest total photon flux for the specific region was used for reporting. For ex vivo BLI, the total photon flux in the isolated organs was measured by using a circular ROI for the lungs or brains (diameter 2. 4 cm), both kidneys (1. 4 cm diameter) or a rectangular ROI for the spleen (1.
Quantification of lung μCT data Quantification was performed similarly to a previously described protocol  (Vande Velde et al. , 2016). All software was provided by the scanner manufacturer (Bruker micro-CT, Kontich, Belgium). The acquired lung scans were sorted to different phases in the breathing cycle (TSort, version 1. 2. 01) to reduce breathing artifacts, as previously described  (De Langhe et al. , 2012). Images were reconstructed by using the NRecon software (version 1. 6. 10. 4) with the following parameters: Gaussian smoothing of 1%, beam hardening correction of 10%, and individual optimization of post alignment settings and ring artifact reduction (3% for all scans). We used an automated segmentation algorithm to quantify the connected aerated lung tissue for all four phases of the breathing cycle, as described in De Langhe et al.
(  2012 ) with minor adaptations. The dataset from the phase of the breathing cycle that corresponded to the end-expiratory volumes was selected for further data processing. ROIs covering the lungs but excluding the heart and main blood vessels were manually drawn on selected coronal images using the interpolation tool in CTAn software  (version 1. 16. 3). The resulting volume of interest (VOI) was converted to a binary dataset by setting a fixed threshold of 73 on a scale of 0-255 in the grayscale index histogram. This allowed for segmentation of the air in the lungs (aerated lung volume, threshold 0-73) and the total lung volume (0-255). The residual volume (threshold 74-255), referred to as the tissue-lesion volume, includes both the normal tissue in the lungs (e. g. interstitial tissue and vessels) and the additional tissue deposited by the pulmonary infection.
Statistical analysis All data were analyzed using GraphPad Prism (version 5. 04, GraphPad Software Inc. , San Diego, CA, USA). A two-tailed P-value of <0. 05 was considered statistically significant. Statistical analysis of BLI and CFU data was performed on the log-transformed values for total photon flux and CFU counts. A two-way ANOVA with Bonferroni post-test was performed to compare the in vitro BLI signal for every cell concentration to the average background signal. Cross-sectional studies were analyzed using an unpaired t-test or one-way ANOVA. For longitudinal studies with available baseline values, a one-way repeated measures (RM) ANOVA was performed. A twoway RM ANOVA was used when comparing multiple infection groups or when comparing to uninfected controls, thereby assuming that the latter values would remain constant during the whole study period.
Funding This work was funded by the  European Commission   ERA-NET  project 'CryptoView' (third call of the  FP7 program  Infect-ERA), the  Research Foundation-Flanders (FWO ;  Fonds Wetenschappelijk Onderzoek ;  1506114N ) and  KU Leuven  [ PF 10/017  (IMIR),  CREA/14/015 ]. L. V. is a PhD fellow strategic basic research at the FWO (151313). J. P. received a PhD grant for strategic basic research from the  Agency for Innovation by Science and Technology (IWT ,  141230 ). G. V. V. received a postdoctoral fellowship from the  FWO  ( 12N7615N ).
We have recently provided the first data on the experimental identification of type I TA systems in C. difficile genome  [23]. In contrast to more easily defined type II TA protein families, the direct search for type I TA components including RNA antitoxins remains difficult. By combining in silico prediction and genome-wide promoter mapping, we have recently identified more than 200 ncRNAs in C. difficile  [25, 26]. The analysis of these deep-sequencing transcriptomic data for the antisense RNAs that overlap the genes encoding small proteins of unknown function allowed us to describe six potential TA loci in the laboratory strain 630∆erm  [23]. Three of these TA modules, i. e. , CD2517. 1-RCd8, CD2907. 1-RCd9, and CD0956. 2-RCd10, were composed of the overlapping toxin and antitoxin genes in convergent orientation and have been characterized in some detail.
Neuroelectric discharges are captured by gold standard data of epileptic patients recorded via intracranial electrodes. Brain areal dynamics is derived from the mean activity of neural populations via neural mass models able to capture the details of the autonomous slow evolution of interictal and ictal phases. Personalized brain network models are then derived for 15 patients. We systematically investigate all possible realizable disconnections of the epileptogenic zone and demonstrate that for all patients a partial targeted disconnection, accounting for the resection of one or a few pathways, is sufficient to stop seizure propagation in the brain, systematically reducing invasiveness and outperforming generic (non-personalized) procedures.
A. Patient selection and data acquisition We selected 15 drug-resistant patients (9 females, 6 males, mean age 33. 4, range  with different types of partial epilepsy accounting for different EZ localizations. All patients underwent a presurgical evaluation (Supplementary Table  1 ). The first phase in the evaluation of each patient is not invasive and comprises of the patient clinical record, neurological examinations, positron emission tomography (PET), and electroencephalography Further elaboration on the EZ are done in the second phase, which is invasive and consists and cliques that are likely to share specialized information. The measures of integration refer to the capacity of the network to rapidly combine specialized information from not nearby, distributed regions. Integration measures are based on the concept of communication paths and path lengths, which estimate the unique sequence of nodes and links that are able to carry the transmission flow of information between pairs of brain regions.
Acknowledgments S. 0. acknowledge  Benjamin Lindner ,  Dionysios Perdikis ,  Timothée Proix ,  Marmaduke Woodman  for useful discussions. This work was partially supported by The  Short Term Mobility Programm  founded by the  Italian National Research Counsil  (protocol number  0057676 , date  31/08/2015 ) and by the  Project Epinext -Fédération Hospitalo-Universitaire (FHU)  " Epilepsy and Disorders of Neuronal Excitability ".
The consequences of digoxin treatment on alternative mRNA splicing were thus explored more comprehensively using deep RNA sequencing, comparing DM1_MSCs with or without treatment with 50 nM of the drug over a period of 2 days. Analysis of annotated splice junctions identified 44 modified splices with Delta c R 20 and 258 with 10 % Delta c % 20 (Tables  S1  and S2 ). The comparison of this dataset with a recently published list of genes, which exhibited dysregulated alternative RNA splicing in muscle biopsies from patients with DM1  (Nakamori et al. , 2013) , revealed a beneficial effect of digoxin treatment on 10 different DM1-specific splicing defects as determined by qRT-PCR analysis (Figure  4 ). Finally, the effect of digoxin was evaluated in vivo, in the HSA LR transgenic DM1 mouse model, which expresses 220 CUG repeats in skeletal muscle and exhibits dysregulated alternative splicing  (Mankodi et al.
, 2010)  and, more recently, the anti-diabetic drug metformin  (Laustriat et al. , 2015). Interestingly, the mechanism of action for cardiac glyocosides differs from that for these previously mentioned   S3. Western blot analysis was quantified by using ImageJ software. Data are presented as mean G SD (n = 4) and p value were determined using paired t test. *p < 0. 05, **p < 0. 01. iScience 11, 258-271, January 25, 2019 267 compounds. Cardiac glycosides modulate the Na + /K + ATPase protein complex upon binding and activate downstream signaling pathways via increased intracellular calcium concentrations  (Fontana et al. , 2013) , which can independently induce changes in alternative mRNA splicing patterns  (Razanau and Xie, 2013; Sharma and Lou, 2011; Sharma et al. , 2014). In this case, the molecular mechanisms linking calcium concentration to the modulation of the splicing process may involve chromatin modifications, rather than RNA-binding proteins  (Sharma et al.
DM1 myoblasts have been described to sustain abnormal ERK activity that might be responsible for the defective myogenic differentiation  (Beffy et al. , 2010). It would therefore be interesting to determine whether the digoxin effect on the functional in vitro myogenesis was triggered by a splicing modification or through an ERK1/2 inhibitory effect. In addition, our results also demonstrated that digoxin treatment led to an increased level of the inactive form of GSK3-b (phosphorylated at S9) in DM1_MSCs. Interestingly, inhibition of GSK3-b signaling with tideglusib is actually under clinical investigation in patients with DM1 (ClinicalTrials. gov identifier: NCT02858908). This development was based on different studies demonstrating that the active GSK3-b is elevated in skeletal muscle biopsy samples from patients with DM1 and in skeletal muscle of mice.
Figure6. Continued Medium without calcium was added 30 min before the digoxin (n = 3). Data were analyzed with one-way ANOVA followed by a Bonferroni post-hoc test. *p < 0. 05, **p < 0. 01, ***p < 0. 001. (D) Effect of different concentrations of digoxin on mitogen-activated protein kinase and mammalian target of rapamycin (mTOR) signaling pathways. Expression level of key modulators of Akt/mTOR signaling in DM1_MSCs treated with different concentrations of digoxin for 48 hr, including Phospho(Ser473)-Akt, Phospho(Ser21/9)-GSK3a/b, Phospho(Ser235-236)-ribosomal protein S6 (rpS6), Phospho (Thr202/Tyr204) ERK, and the corresponding total forms. Antibodies used are liste in TableS3. Western blot analysis was quantified by using ImageJ software. Data are presented as mean G SD (n = 4) and p value were determined using paired t test.