dataesr/scientific-paragraphs-categorization huggingface dataset:
We confirm that all methods were performed in accordance with the relevant national guidelines and regulations. In accordance to the national law on the protection of individuals taking part in biomedical research, patients were informed by their referring oncologist that their biological samples could be used for research purposes and they gave their verbal informed consent. This study was approved by the institutional review board and ethics committee of the Institut Curie Hospital Group. Data availability statement. The datasets generated during and/or analysed during the current study are available from the corresponding author upon request.
001). Figure  3D  shows that the fraction distributed along the tubules of the non-malignant melanocytes Hermes 2B-GFP was 44. 81% at 2 hours and increased up to 71. 01% and 74. 73% at 12 and 24 hours after plating, respectively (n = 10). Also in this case, the values obtained at later times were highly significant if compared with the first time-lapse (P < 0. 001). Therefore, the results obtained for cutaneous and uveal melanoma were comparable to the ones obtained for Hermes 2B-GFP, probably due to similar angiotropic properties of these cells. We then quantified the velocity of melanoma cells involved in extravascular migration and compared it to the velocity of non-malignant melanocytes. For this purpose, the average velocity of at least 48 cells for each cell line was calculated, employing the Manual Tracking plug-in of the ImageJ software.
Acknowledgements We thank  Philippe Herbomel  for the zebrafish transgenic line Tg(kdrl:Hsa. HRAS-mCherry). We also thank  Dorothy Bennett  for the non-malignant human melanocyte cell line Hermes 2B. We thank  Shahad Albadri  and  Karine Duroure  for the technical help given respectively for the Live Imaging and zebrafish injections. We also thank  Roberta Ragazzini  and  Aude Battistella  for sharing reagents and protocols for the Lentivirus production and infection. We thank  Marc Henri Stern ,  Manuel Rodrigues , all members of  Del Bene's laboratory and the ones of Alsafadi's laboratory  for fruitful discussions and suggestions. We thank  Michele Scotto di Mase  for the help with GraphPad Prism. We finally thank the  Developmental Biology Curie imaging facility (PICT-IBiSA@ BDD, Paris, France ,  UMR3215/U934 ) member of the France-BioImaging national research infrastructure for their help and advice with confocal microscopy and 3D reconstruction of videos.
Objective Self-exclusion is one of the main responsible gambling tools. The aim of this study was to assess the reliability of self-exclusion motives in self-reports to the gambling service provider. settings This is a retrospective cohort using prospective account-based gambling data obtained from a poker gambling provider. Participants Over a period of 7 years we included all poker gamblers self-excluding for the first time, and reporting a motive for their self-exclusion (n=1996). We explored two groups: self-excluders who self-reported a motive related to addiction and those who reported a commercial motive. results No between-group adjusted difference was found on gambling summary variables. Sessions in the two groups were poorly discriminated one from another on four different machine-learning models.
5 As a consequence, recall and recruitment biases have been major issues. Some studies on online gamblers have suggested a surprisingly moderate percentage of problem gamblers (68%),  6  contested by other surveys reporting up to 95% problem gamblers among offline self-excluders. 7 Some studies have pointed to heterogeneity among self-excluders. 6 o date, no prospective information on motives for self-exclusion has been made available. However, two studies on online self-exclusion have used prospectively recorded account-based gambling data. 8 9 Accountbased gambling data offer the opportunity to strengths and limitations of this study ► This is the first study prospectively documenting self-reported motives for self-exclusion. ► Our study systematically included self-excluders who reported a motive during the usual self-exclusion process, limiting self-selection bias.
► No information on offline gambling and gambling on other websites was available. ► No comparison group was included in the analysis. The efficacy of self-exclusion should be assessed in a future study comparing self-excluders with matched non-self-excluders. Open access report gambling behaviours on a website objectively and with no recall bias. Data of this type have been reported in other contexts to describe problem gambling behaviours. 10 11 Dragicevic et al showed that self-excluders (n=347) on average sustained higher losses and presented riskier behaviours than controls. However, for technical reasons, these authors chose to include only mono-self-excluders and self-excluders for at least 30 days. 8 They found a high rate of very quick self-excluders (25% within a day). On the other hand, Xuan and Shaffer demonstrated a change in gambling behaviour in the days prior to self-exclusion.
9 nfortunately, no follow-up data were available in these studies. Effectiveness analyses have been reported among pathological gamblers in land-based gambling venues and remain scarce and generally concern self-selected samples. To date, despite methodological issues and weak evidence, self-exclusion has often been presented as a therapeutic tool in itself. If previous studies demonstrated significant changes among pathological gamblers in land-based gambling venues from before exclusion to after exclusion, no comparative data are available to state on the efficacy of self-exclusion. 12 Poker gamblers could be a particularly interesting population in which to explore self-reported motives for self-exclusion, as they present particularities in terms of feelings of belonging to a gambling community and frequently claim a passion for the activity rather than problematic behaviour.
Measures We collected data retrospectively from different prospective databases systematically recorded by the gambling service provider: (A) Gambler data: self-excluders' basic demographics (gender, age, date since opening of the account), characteristics of self-exclusions (date, self-reported motive) and gambling summary variables in the month prior to self-exclusion (details of deposits, and basic betting activity in the month) (ie, the amounts bet). We chose to explore the month before each self-exclusion for several reasons. First, the short period before self-exclusion has been reported to be characterised by an increase in gambling involvement in cases where self-exclusion is related to gambling problems. 9 These authors used a 23-day period, considered to be relevant for most of their sample.
Other studies chose to explore a 1 month period. 8 In a previous study on poker gamblers we examined account-based gambling data in the previous month and were able to demonstrate that it was predictive of problem gambling as assessed with a classic screening tool. 11 Most employed people in France receive their income once a month. It is therefore important to capture at least 1 month to avoid any artificially enhanced gambling activity resulting from a possible effect following receipt of income. (B) Session characteristics: starting date, end date, duration. Sessions were defined as gambling with no time span >10 min with no action. (C) Cash game and tournament gambling data at table level for players with real money. Winnings were computed from table data (cash game winnings+prize amount for tournaments-buy-in-plus-rake for tournaments).
Analysis We present data for the whole sample and for two groups: those with a first self-exclusion for a motive related to addiction (group 1) and those with a first self-exclusion for commercial motives (group 2). Our hypothesis was that group 1 would demonstrate more intense gambling behaviour before the first self-exclusion and a more deleterious course than group 2. We present results on three levels: 1. Gambling summary variables for the month prior to the first self-exclusion, and to the second self-exclusion if there was a second one. We described and compared sociodemographics and gambling summary variables in the month before the first self-exclusion between subjects who self-excluded for addiction and those who self-excluded for commercial reasons, by bivariate and multivariate analyses (logistic regression).
22. Return to gambling on the website. We ran a mixed model for repeat measurement analyses, comparing the course of the winnings over 4 months after the return to gambling between the two groups, testing an interaction between time and group as a fixed effect, and random subject and time effects (R3. 4. 3 software, lme4 package). For this model, missing data on the variables concerning winnings, meaning no winnings because no gambling with real money over the period, were completed as 0. The p value was obtained by performing an analysis of variance between this model and the null model.
dIsCussIOn Our study presents account-based data on gambling characteristics and first self-exclusion motives of 1996 poker gamblers. It is the largest sample of self-excluders ever reported. The inclusion of self-excluders was systematic over 7 years, and motives were collected prospectively, avoiding any recruitment or recall bias. Follow-up was documented objectively and was studied up to the second month after return to the website. We demonstrated that self-excluders were very heavy gamblers, that self-exclusion was mostly a non-unique event and that its protective effect seemed temporary, suggesting a deterioration in practice within 2 months for those returning to the website. Motives for self-exclusion self-reported to the gambling service providers did not seem very relevant. Both groups were very heavy gamblers in terms of financial outlay (€716 deposited in the month on average).
29 he promotion of self-exclusion also differs between countries. 23 Self-exclusion could be actively proposed for excessive gamblers screened online. limitations As mentioned above, in France, no guidance at all is provided to accompany self-exclusion: our follow-up data concern only the self-exclusion measure and the 4 months after a return to the website. Gamblers who self-excluded could however benefit from external assistance, and we have no information on this score. Further to this, no information on gambling offline or gambling on other websites was available. Mixed gambling activity was explored through sports betting activity, but other forms of gambling were not documented. However, while the amounts involved could be underestimated, we consider that the dynamic of losses on the website is indeed informative on the control a person has over gambling activities.
Cwp19 is a putative surface-associated protein of 703 amino acids with a predicted molecular weight of 77. 8 kDa and a pI of 8. 99. This protein has a putative 24-amino acid signal sequence, a C-terminal domain containing three tandem copies of the cell wall binding motif CWB2 (Pfam04122), and a putative N-terminal catalytic domain belonging to the glycosyl hydrolase-like 10 family (GHL10) (Pfam02638) (Fig. 1B ). Cwp19 is conserved in every genome available for C. difficile. Moreover, the GHL10 domain is widely distributed in bacterial species (Table  S2 ). At the time of our study, we found in the Pfam database 1,642 GHL10 domain-containing proteins from 871 organisms  (42). These proteins are frequently found in members of the Gram-positive phyla Firmicutes and Actinobacteria as well as in Gram-negative bacteria, including members of the phyla Bacteroidetes, Cyanobacteria, and Proteobacteria.
We found instead putative Ϫ10 (TATACT) and Ϫ35 sequences (TTGACA), resembling those of A -dependent promoters. In addition, expression of cwp19 was not affected in a D mutant  (51). Overall, these results suggest that cwp19 is primarily transcribed by A. Impact of cwp19 inactivation on cell separation and autolysis. Light microscopy analysis of cells in the exponential-growth phase revealed no effect on daughter cell separation in the absence of Cwp19 (data not shown). To determine if Cwp19 functions as an autolysin, a Triton X-100-induced-autolysis assay was performed on cells harvested during exponential growth in BHI medium. As shown in Fig. 3C , cellular lysis was rapid when the wild-type cells were resuspended in the presence of 0. 01% Triton X-100. The autolysis of the cwp19 mutant strain was slower than that of the wild-type strain, while complementation of the cwp19 mutant restored the wild-type phenotype (Fig.
Supernatants were pooled into a clean 96-well plate. Peptide extracts were then dried and solubilized in starting buffer (3% CH 3 CN-0. 1% formic acid-water) for chromatographic elution. Peptides were analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass spectrometer equipped with an HPLC-chip cube interface (Agilent Technologies, Massy, France). The tandem mass spectrometry peak lists were extracted using the DataAnalysis program (version 3. 4, Bruker Daltonics) and compared with the protein database using the Mascot Daemon (version 2. 1. 3) search engine. The searches were performed with a maximum of one missed cleavage, with no fixed modifications, and with variable modifications for carbamidomethyl and oxidation of methionines. The identifications from the tandem mass spectrometry spectra were performed with mass tolerances of 1.
ACKNOWLEDGMENTS We thank  Fanny Quenette  and  Cléa Barberon  for technical assistance and  Isabelle Martin-Verstraete  and  Yannick Tremblay  for comments on the manuscript. Protein identification by ESI-LC-MS/MS was performed on PRIMACEN (http://primacen. crihan. fr), the  Cell Imaging Platform of Normandy, IRIB, Rouen, France. This work was supported by the  University of Rouen  and the  University of Paris-Descartes. J. Peltier  is funded by a  Pasteur-Roux  fellowship. The work of  P. Courtin  and  M. -P. Chapot-Chartier  was supported by  INRA. The manuscript is dedicated to  Jean-Louis Pons , who passed away on 4 August 2015. He was a mentor, and his guiding voice is deeply missed.
Statistical Analysis Comparisons were done using the χ 2 test or Fisher's exact test for categorical variables and the Wilcoxon test for continuous variables. Incidences of HSV-1 and HSV-2 infections were compared between groups with mid-P exact. We calculated 95% confidence interval (CI) for incidence by use of a Poisson distribution. We did analyses with Stata/SE 12. 1 software and SAS software version 9. 3. All P values and 95% CIs are 2-sided.
Acknowledgments Financial support. The  ANRS IPERGAY Trial  was funded by  ANRS , the  Canadian HIV Trials Network   CTN268 , the  Fonds de Dotation Pierre Bergé pour la Prévention   AP-FPB-2012/05 , and the  Bill and Melinda Gates Foundation   OPP1106343. Gilead Sciences  donated the tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) and placebo used in the study and funding for the pharmacokinetics analysis. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the  ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Recruitment Patients were ascertained from neurology clinics. The study included published and unpublished clinical data from Families 13 to 16, reported previously as 314-1, 979-1, 1044-1, and FIGURE 1: Schematic representation of titin isoforms and location of patient mutations. (A) Size (relative to number of amino acids) of the 4 main titin regions encoded by the inferred complete metatranscript (Refseq transcript NM_001267550. 1), the single characterized skeletal muscle isoform N2A (Refseq transcript NM_133378. 4), the principal cardiac long isoform N2BA (NM_001256850. 1) and the principle cardiac short isoform N2B (NM_003319. 4). The Z-disc region of titin (green) interacts with a-actinin, telethonin, and other Z-disc-related proteins. The I-band region (blue) contains multiple tandem immunoglobulin-like domains and the "PEVK" domain (yellow), which is rich in proline (P), glutamic acid (E), valine (V), and lysine (K).
Family members were Sanger sequenced to confirm segregation and carrier status. The Leiden Muscular Dystrophy (http://www. dmd. nl/), ClinVar (https://www. ncbi. nlm. nih. gov/clinvar/), and Cardiodb mutation databases (http://cardiodb. org/titin/) were interrogated to identify previously reported mutations. The Exome Aggregation Consortium (ExAC) database (http://exac. broadinstitute. org/) was used to determine the frequency of each mutation in the general population. AlamutV R Visual (Interactive Biosoftware, North Seattle, WA) was used to predict the impact of splice site mutations.
Clinical Features Analysis The clinical analysis cohort included patients with 2 Sangerconfirmed nonsense, frameshift and/or splice site mutations shown to be in trans by segregation studies. The single exception was the Family 7 proband, who had a homozygous mutation and history of parental consanguinity; however, parental DNA was unavailable. The data from clinical analysis cohort members (henceforth referred to as patients) were collected from primary medical records and managing clinicians, tabulated, and the percentage of patients with each feature calculated. The denominator for each calculation (shown in Table  1  and Supplementary Table  2 ) was the number of patients for whom data were available for that feature, rather than total cases. As patients "unknown" for any feature are more likely to have been negative than positive for that feature, this approach may have resulted in a small overestimation of prevalence.
Cardiac Isoform Analysis The Cardiodb database (http://cardiodb. org/titin) was interrogated to determine which mutations were predicted to alter the 2 most abundant adult cardiac isoforms, N2BA and N2B. Families were stratified according to the cardiac status of affected members ("Yes" 5 cardiac involvement in at least 1 member), and whether each had (1) 2 mutations predicted to alter both N2BA and N2B or (2) other combinations of mutations. Significance was determined using Fisher's Exact Test.
"  14 Deep tendon reflexes were normal in a single cohort member with congenital contractures (camptodactyly and talipes) but no history of limb weakness (Family 19 proband). 15 Ptosis was typically mild, occasionally unilateral, and congenital in at least 1 cohort member. 16 Data regarding these features were not specifically requested during the formal data collection process but were reported spontaneously in descriptive data for >1 cohort member and were therefore noteworthy. As dataset is incomplete, a denominator and percentage are not provided. 17 In a small subset of additional cases, rotational deformity of the spine had resulted in prominence of one side of the chest wall. These were counted as "no/absent" for chest wall deformity. 18 "Respiratory insufficiency" is defined as reduced force vital capacity and/or oxygen requirement and/or ventilation requirement.
19 Only 2 cohort members with respiratory insufficiency had no scoliosis or chest wall deformity. One was a 9-month-old infant on full-time ventilation who may yet develop truncal deformities. The other was a 32-year-old male who was lost to follow-up from age 17 years. 20 Diaphragmatic/paradoxical breathing pattern data were available for only 12 cohort members (incomplete data ascertainment). This feature could not be assessed in severely affected infants requiring full-time ventilatory support. 21 Many cohort members had not been screened for osteopenia at the time of ascertainment. 22 Mild intellectual disability was reported in 2 brothers from Family 26; 1 also had attention-deficit/hyperactivity disorder. 23 One cohort member had undergone 4 separate surgical procedures, and several had undergone 2 procedures.
Families 28-31 have a range of congenital titinopathy-like clinical features (as shown in Supplementary Table  3 ), but inconclusive segregation results due to absence of carrier status data from one parent (Families 28 and 29) or absence of either mutation in one parent (Families 30 and 31). FSV, IN, cores, and "other" structural features are defined in "Results: Muscle Pathology. " Cases with 1 metatranscript-only mutation had similar histopathological and ultrastructural findings to other segregation-confirmed cases, although none had "classical" centronuclear myopathy features. The segregation-inconclusive case muscle biopsies had similar histopathological features to those in segregation-confirmed cases. When no slides were available for review and no EM had been performed, descriptions of both moth-eaten fibers or central lucencies suggestive of cores on oxidative enzyme stains were recorded as cores.
Acknowledgment The following authors were supported by the  Australian NHMRC :  N. G. L. ( APP1117510 ),  E. C. O. ( APP0633194 ,  APP1090428 ),  G. L. O. ( APP1056285 ),  R. G. ( APP1074954 ), and G. R. ( APP1122952 ). Additional author funding was provided by  Muscular Dystrophy NSW  (G. L. O. and R. G. ), the  Royal Australasian College of Physicians  (G. L. O. ), and the  Government of Western Australia Department of Health FutureHealth WA Merit Awards  (G. R. ). This work was further supported by  NHMRC Project and Centre of Research Excellence Grants  ( APP1022707 ,  APP1031893 ,  APP1113531 ; K. N. N. , N. G. L. , N. F. C. , S. C. ); the  Association Francaise contre les Myopathies  ( 18724 ); the  National Heart, Lung and Blood Institute  ( R01 HL115988 ; H. G. ,  UM1 HG008900 ; D.
Instrumentation: Handheld Raman Spectroscopy. Metrohm Instant Raman Analyzer (MIRA, Metrohm, France) was used to obtain Raman spectral acquisitions. The excitation source was a 785 nm single-mode diode laser generating a maximum of 75 mW on the sample. Analyses were conducted using the vial module at a focal distance of 1. 0 mm with the orbital raster scan (ORS) system. The use of ORS technology allows analyzing a larger volume of the sample which leads to increase in the accuracy, repeatability, and reliability of the measurements. The spectral region studied was 400-2300 cm -1 with a spectral resolution from 12 to 14 cm -1 and acquisition time was 8 seconds. Spectral acquisition and data preprocessing were conducted with Metrohm Mira software (Metrohm, France). Samples were analyzed in glass vials in triplicate in order to include container-induced variability.
2. 4. Chemometric Analysis. Raman spectra were normalized over the entire spectral area from 400 to 2300 cm -1. All data were analyzed with a principal component analysis (PCA) to highlight and exclude aberrant spectra. MATLAB5 7. 12. 0 (R2011a) software was used for chemometric analyses. Calibration models for qualitative and quantitative analyses were developed, optimized, and validated according to Guidelines of the Use of NIRS by the Pharmaceutical Industry published by the European Medicines Agency  [23]. Three sets were constituted: (i) a calibration set for creating the calibration model, (ii) a calibration test set for internal validation and optimization of the model, and (iii) an independent validation set for external validation of the model. According to EMEA guidelines, the calibration test set was grouped to the calibration set to increase the variability in the calibration set, thus the robustness of the models.
Information technology used in the design of the TASK feasibility RCT We designed the TASK trial procedures using Research Electronic Data Capture (REDCap), a secure web-based database management application  [20]. We created three Fig. 2  TASK feasibility trial schematic websites, one for recruitment (www. task4stroke. org) [21] , one for the TASK-CBT intervention and one for the comparator TASK-Relax using an industry-led website builder. Using REDCap, we embedded data collection forms in our websites for self-screening for eligibility, informed consent and online tasks for TASK-CBT. Usage of all websites is monitored with Google Analytics. In our smartwatch sub study, we are testing the feasibility of GENEActiv Original smartwatch  [22] , a device designed primarily for research with validation data  [22].