dataesr/scientific-paragraphs-categorization huggingface dataset:
Strengths and Weaknesses of the Study Compared to Other Studies (External Validity) We focused on AP-HP sponsored studies and therefore on a single geographic region (the Paris conurbation), which may limit the external validity of our findings. However, the AP-HP is the leading academic sponsor in France and the leading research center in Europe. Moreover, the results of our study highlight issues that are not specific of the AP-HP institution. Indeed, burdensome regulatory requirements  [3, 25, 36] , pharmaceutical issues  [1, [37] [38] [39] , and difficulties in establishing contracts with pharmaceutical companies  [25]  have been reported internationally. Numerous publications address off-label and unlicensed drug use in pediatrics  [1, 2] , the continuing paucity of data on pediatric formulations  [37, 40] , and other difficulties in obtaining ageappropriate drug formulations for the pediatric population  [38, 39, 41].
To assess the impact of the increase in rRNA levels and the number of ribosomes on parasite growth and proliferation, we monitored the progression of parasitemia (% of infected erythrocytes) of PfSir2a-disrupted parasites in parallel with that of wild-type. Starting from the same parasitemia, PfSir2a-disrupted parasites produced reproducibly significantly higher parasitemia than wildtype parasites (2-3-fold increase after three cycles, Po0. 01, Wilcoxon test; Fig. 2a ). These data show for the first time a link between rRNA gene transcription and Plasmodium growth rate. We further addressed the question if the increased multiplication rate is due to a shortened asexual blood-stage cycle or due to higher number of daughter merozoites generated per erythrocytic schizont. Wild-type and the mutant parasites maintained a similar parasite asexual cycle duration (47.
3a ). As for the complemented parasites, we examined the resistant parasites by qRT-PCR to confirm the increase in PfSir2a transcript levels, and by microscopy to monitor the expression and localization of the PfSir2aHmCherry fusion protein (data not shown). The episomal PfSir2a overexpression in wild-type parasites resulted in significantly lower number of merozoites per schizont (12. 3±2. 8, Po0. 0001, M-W test; Table  1 ), as well as lower levels of parasitemia than those of wild-type or the transfection control parasites (Po0. 0001 and Po0. 001, respectively, M-W test; Fig. 4a , Table  1 ). In terms of rRNA synthesis, the transcript levels of A1 and A2 rRNA genes were approximately two-fold downregulated, whereas pre-rRNA transcript levels of S-types appeared unchanged (Fig. 3c ), suggesting that in blood-stages the S-type rRNA genes are completely repressed.
The medium for transgenic lines contained the following drugs: 3D7DSir2a, 2 mM PYR; 3D7 þ Sir2aHmCherry and 3D7 þ vector, 2. 5 mg ml À 1 BSD; 3D7DSir2a þ Sir2aHmCherry and 3D7DSir2a þ vector, 2. 5 mg ml À 1 BSD and 2 mM PYR. Samples were collected every 24 h for staining with Giemsa and/or the fluorescent DNA-specific dye SYBR Green I  39, 40. To determine parasitemia in the Giemsa-stained thin blood smears, images of 1,000-2,000 erythrocytes were randomly acquired and the percentage of infected erythrocytes counted semiautomatically using ImageJ (http://rsbweb. nih. gov/ij/). This software was also used for counting of the number of merozoites per schizont on Giemsa-stained smears. The SYBR Green I stained samples were analysed on a CyFlow SL Blue (Partec) flow cytometer and the data evaluated using FlowJo software (TreeStar) to determine the percentage of infected erythrocytes.
Parasite cycle duration analysis. To determine cell-cycle length, we used highly synchronous 4% haematocrit cultures at 0. 1% parasitemia. Fifty microlitre of culture was collected every 2-3 h and stained with SYBR Green I as above. The distribution of parasite stages of each sample was analysed by flow cytometry for DNA content. As defined previously  41  , the cycle time corresponds to the duration between two peaks of schizonts. To calculate the percentage of schizonts we gated on parasites showing N44 (N is the number of nuclei). The values were plotted against time and fitted to a sine wave function using GraphPad Prism software with the following equation: Y ¼ m1 þ amplitudeÃ sinðð2ÃpiÃX=wavelengthÞ þ m2Þ Y is the percentage of schizonts, X is the time, m1 is the shift in the y axis, m2 is the shift in the x axis and wavelength is the cycle length.
Fluorescence microscopy. Immunofluorescence assays were performed as previously described  15  in ring-stage parasites. Antibody dilutions were as follows: anti-PfSir2a, 1:100; anti-mCherry (Abcam, ab-62341), 1:5,000; and anti-rabbit highly cross-absorbed Alexa-Fluor-488-conjugated (Invitrogen), 1:500. Images were taken using a Nikon Eclipse 80i microscope with a CoolSnap HQ2 camera (Photometrics). NIS Elements 3. 0 software (Nikon) was used for acquisition and ImageJ for composition. Electron microscopy. Infected erythrocytes were fixed in 1% glutaraldehyde in RPMI-HEPES, and embedded in LR Gold resin (London Resin Company Ltd, UK) as previously described  42. Ultrathin sections of 55 nm were collected, stained with 4% uranyl acetate and observed by using a JEOL JEM-1200EX electron microscope.
Quantification of ribosomal content was performed as described  43  by manually counting of the number of ribosomes in defined areas of the cytoplasm (squares of 0. 2 Â 0. 2 mm 2 ) using ImageJ. The average of at least three squares per parasite was calculated and expressed as ribosomes per square micrometre. Transcript analysis. Total RNA was isolated using the Trizol method from ringstage synchronized cultures (stage at which Pol I transcription is greatest  29  ). As rRNA gene transcription is very sensitive to temperature changes 10 , all the operations prior Trizol extraction were performed at 37 °C, except for experiments on Supplementary Fig. S4 , which were carried out at room temperature. Extracted RNA was DNAse treated, reverse transcribed and analysed by quantitative PCR (qPCR) using the set of primers designed in a previous work  29.
DDCt analysis was used to calculate the relative expression of each rRNA gene, normalized to the geometric mean of three reference genes: PFB0295w, PF07_0073 and MAL8P1. 151 (www. plasmodb. org). The selected three genes satisfy the following criteria: unchanged in the 3D7 versus 3D7DSir2a  11  , unchanged over the 48 h cycle and expression in fair abundance. The sequence of primers is listed in Supplementary Table  S1. ChIP analysis. The ChIP assay was performed in ring-stage synchronized parasites using a previously described protocol  26. Immunoprecipitation was performed at 4 °C overnight with a 1:100 dilution of anti-H3K9ac (Upstate, 07-352). Immunoprecipitated DNA was analysed by qPCR, as described above. qPCR was also performed in dilutions of purified input DNA, to calculate the amount of target sequence in immunoprecipitated chromatin relative to the amount of target sequence in input (% of input).
Acknowledgements We would like to thank  Alan Cowman ,  David Fidock ,  Neha Issar  and  Maria Mota  for sharing reagents;  Nicolai Siegel ,  Nicholas Malmquist ,  Medhi Ghorbal ,  Raul Sanchez-David ,  Olivier Gadal ,  Ghislain Cabal  and  Maria Rebelo  for helpful discussions. This work was supported by the  Fondation Recherche Medicale ,  European Commission   FP7 programmes EVIMalaR  and  ERC Advanced Grant  ( PlasmoEscape 250320 ). L. M. -S. was supported by  Fundac¸a  ˜o para a Ciencia e a Tecnologia,  EVIMalaR  and  EMBO  long-term fellowships.
The control group included 42 controls whose stools were analyzed in a previous study. 14 ollection of data included age, sex, height, weight and type of antibiotic treatment, but other medications or diet were not collected. According to our published protocols,  16  most of patients (480%) received 6 weeks of treatment. Written consent was obtained from each participant and approved by the ethics committee of the Faculty of Medicine La Timone, Marseille, France under number 08-002.
Analysis of weight change A standardized questionnaire was used to collect demographical, clinical and therapeutic data in all patients treated by antibiotics. The baseline weight (1 month before the onset of the disease), weight at 1 year and height were collected for each patient based on clinical records, systematic follow-up consultations or phone calls. The %deltaBMI, a %deltaBMI 410% and an acquired obesity (BMI becoming430 at 1 year) were assessed comparing baseline BMI and BMI at 1 year. The %deltaBMI was calculated as follows: %deltaBMI ¼ (BMI at 1 year À baseline BMI)/baseline BMI Â 100.
27 b Specific Proteobacteria, enterobacteriaceae and E. coli have been linked with both weight gain and obesity or weight loss or absence of obesity, whereas Bacteroidetes, Bacteroides and bifidobacteria have been linked to a statistical anti-obesity effect. 54  second analysis designed for the identification of gut bacteria predictive of weight gain was performed only for samples obtained during the first week of antibiotics in patients for whom both weight and gut flora data were available. A real-time PCR was performed on a Bio-Rad FLX96 and targeted L. reuteri, L. plantarum, L. rhamnosus, B. animalis and E. coli as previously reported. 13.
Statistical analysis Student's t-test or a Mann-Whitney test was used to compare continuous variables between the two groups according to the distribution assessed by the Kolmogorov-Smirnov test. Proportions were compared using a two-sided Barnard's exact test. 20 The analyses were performed using SPSS v21. 0 (IBM, Paris, France). In the first analysis, the changes of BMI at 1 year were compared between the two antibiotic groups (vancomycin or amoxicillin) for all patients with available information. A logistic regression analysis was performed, using a deltaBMI 410% or acquired obesity as the dependent variable. The regression was adjusted by age, sex, surgery and baseline BMI, and was systematically adjusted by antibiotic treatment (vancomycin or amoxicillin). In the second analysis, the concentrations of Bacteroidetes, Firmicutes, M.
The tactile vision substitution system (TVSS) The visuo-tactile device used for the training was the PTD version of the TVSS. The PTD prototype has been developed and constructed by the Electronic Vision Group at the Kirchoff Institute for Physics of the University of Heidelberg along with the dedicated Visor software (V2. 0) working in PC environment  (Zappe et al 2004). This PTD is a nonmagnetic device specially designed to be used for both behavioural and anatomo-functional studies ran in the high magnetic field of an f MRI environment (so that it does not disturb the image acquisition). The PTD is made up of five following elements (see figure  1 ). The Visor software can receive images from a webcam (Philips ToUcam XS) and allows one to generate patterns by a paradigm script or interactively on the PC.
| Artificial intelligence Machine learning is a broad term of artificial intelligence derived from the extraction of patterns from large data sets. The marriage with healthcare analytics and decision processes has been rapidly forwarded with computerized medical records and the creation of large data warehouses. A deep neural network was created to analyse raw ECG data from an ambulatory heart monitor and classify it into 12 categories based upon the presence of arrhythmia. Machine learning performed very well with an average under the reviewer operating characteristic curve (ROC) of 0. 97 and an average F1 score (mean of the PPV and sensitivity) of 0. 837; a score better than an average cardiologist (0. 780). 137 chine learning has been applied to standard ECG characteristics in sinus rhythm to predict incident AF using the eight independent ECG leads (leads I, II, V1-6) through a convolutional neural network.
138 The ROC area under the curve for the detection of AF was 0. 87 (0. 86-0. 88) using the internal validation dataset and 0. 87 (0. 86-0. 88) using the testing dataset. In an analysis of the Atrial Fibrillation Prediction Database, a machine learning approach based upon heart rate variability predicted onset of AF with sensitivity of 100%, specificity of 95. 6%, and accuracy of 96. 2%. 139 Machine learning based upon ECG characteristics identified left ventricular dysfunction with an area under the curve of 0. 93, sensitivity of 86. 3%, and specificity of 85. 7% including risk of left ventricular dysfunction in those without. 140 chine learning has shown accuracy in predicting mortality and risk stratification of patients with CAD. 141 Machine learning has also been shown to accurately discriminate between athletic hearts compared to hypertrophic cardiomyopathy hearts.
| Patients who have undergone cardiac surgery While post-cardiac surgical AF likely occurs as a result of the interaction between acute perioperative triggers and the underlying atrial and cardiac substrate, its occurrence identifies a subset of patients associated with long-term morbidity and mortality. In a study of patients who underwent CABG, post-operative AF conferred an eight-fold increased risk of future AF and doubled cardiovascular mortality on long-term follow-up. 199 Follow-up rhythm monitoring, for example with ECG or Holter monitoring is advisable in this subset of patients particularly in the setting of symptom development. There is emerging data on the use of implantable cardiac monitors for long-term monitoring of this subset of patients. While implantable cardiac monitors allow continuous long-term monitoring for arrhythmias and asymptomatic arrhythmias, the risk-benefit ratio is balanced by the arrhythmia detection rate beyond the immediate post-operative period and level of invasiveness of the monitoring device.
383, 390 ttle data exist on how to assess risk of VT/VF in inflammatory cardiomyopathies. Besides EF, which is used for all non-ischaemic aetiologies, no randomized studies have evaluated other parameters or even EF as a predictor of VT in different inflammatory cardiomyopathies. In particular, certain inflammatory cardiomyopathies may carry higher risk than others (sarcoidosis vs. viral myocarditis). Risk of ICD therapy may be as high as 15% per year in biopsy proven cardiac sarcoidosis patients. 391 Although randomized data on use of higher EF in these patient populations is lacking, given risk of VT noted in retrospective studies, use of MRI and cardiac PET to evaluate aetiology of non-ischaemic heart disease is warranted, and treatment of inflammation to reduce risk of VT is advised. Furthermore, cardiac PET and MRI can be used to assess for recurrent inflammation or progression of disease on treatment.
going randomized trials as the Optimal Anticoagulation for Higher Risk Patients Post-Catheter Ablation for Atrial Fibrillation Trial (OCEAN) (NCT02168829) and the Prevention of Silent Cerebral Thromboembolism by Oral Anticoagulation with Dabigatran After Pulmonary Vein Isolation for Atrial Fibrillation (ODIn-AF) trial (NCT02067182). Until now, one randomized trial showed that ablation therapy for AF in patients with impaired LVEF was associated with significantly lower rate of death from any cause and worsening HF. 274 Subgroup recommendations may change after the completion of trials studying the effect of ablation on stroke and the need for anticoagulation. Particularly in HF patients, it remains to be seen in which subgroups of patients the data indicating mortality reduction after AF ablation are applicable.
Currently, we have no data on how the Triggered by cough, defaecation, or micturition information provided by PPG-based wearables will affect manage-With head rotation or pressure on carotid sinus (e. g. tumour, shaving, tight collars) ment and outcomes of patients, or how risk scores derived in other electrocardiography monitoring techniques. Accuracy of various de-vices varies, with correlation to reference standard ECG monitoring ranging from 0. 76 to 0. 99. 91 Recent advances in wearable ECG acqui- populations such as the CHA 2 DS 2 -VASc score apply in these previ-Standing from supine/sitting position High-risk ously undetected subjects. sition include use of direct electrode recording that represents a reg-ulatory approved medical device generating a lead I like rhythm strip, blurring the lines between consumer and medical devices.
METHODS The data and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure. Because this study used data from human subjects, the data and everything pertaining to the data are governed by the French Health Agencies and cannot be made available to other researchers. This retrospective cohort study was based on the national hospitalization database covering hospital care from the entire French population. The data for all patients admitted with aortic stenosis in France from January 2010 to June 2019 were collected from the national administrative Programme de Médicalisation des Systèmes d'Information (PMSI) database. Through this program, medical activity is recorded in a database and rendered anonymous. It includes >98% of the French population (67 million people) from birth (or immigration) to death (or emigration), even if a person changes occupation or retires.
This process allows the determination of each hospital's budget, in the 1546 French healthcare facilities for both public and private hospitals. Each hospitalization is encoded in a standardized data set, which includes information about the patient (age and sex), hospital, stay (date of admission, date of discharge, and mode of discharge), pathologies, and procedures. Routinely collected medical information includes the principal diagnosis and secondary diagnoses. In the PMSI system, identified diagnoses are coded according to the International Classification of Diseases, Tenth Revision (ICD-10). All medical procedures are recorded according to the national nomenclature, Classification Commune des Actes Medicaux. The PMSI contains individual pseudoanymized information on each hospitalization that are linked to create a longitudinal record of hospital stays and diagnoses for each patient.
The reliability of PMSI data has already been assessed, and this database has previously been used to study patients with cardiovascular conditions, including those with aortic stenosis treated with TAVR. 1, 2 e study was conducted retrospectively and, as patients were not involved in its conduct, there was no impact on their care. Ethical approval was not required, because all data were anonymized. The French Data Protection Authority granted access to the PMSI data. Procedures for data collection and management were approved by the Commission Nationale de l'Informatique et des Libertés, the independent National Ethical Committee protecting human rights in France, which ensures that all information is kept confidential and anonymous, in compliance with the Declaration of Helsinki (authorization number 1897139).
Study Population From January 1, 2010 to June 30, 2019, 520 662 adults (age ≥18 years) were hospitalized with a diagnosis of aortic stenosis (I350, I352, I060, and I062 using ICD-10 codes) as the principal diagnosis (ie, the health problem that justified admission to hospital), the related diagnosis (ie, potential chronic disease or health state during the hospital stay), or a significantly associated diagnosis (ie, comorbidity or associated complication). For the analysis of TAVR procedures, we included all adults with a single percutaneous procedure (Classification Commune des Actes Medicaux code: DBLF001). Early and more recent generation balloon-expandable (BE) and self-expandable (SE) TAVR were differentiated using their codes used for pricing. Patient information (demographics, comorbidities, medical history, and events during hospitalization or follow-up) was described using data collected in the hospital records.
Our "real life" incidences of pacemaker implantation at 30 days are slightly higher than in the randomized SOLVE TAVR (Comparison of Second-Generation Self-Expandable vs. Balloon-Expandable Valves and General vs. Local Anaesthesia in Transcatheter Aortic Valve Implantation) trial. 9 They were also higher than in an earlier French observational study, considering the hospital phase (16-18%) and using a declarative method that may underestimate the true rates of PPI. 10  Higher rates of in-hospital PPI (up to 22%) were, however, reported in the most recent findings from this declarative registry. 11 his contrasts in part with the findings at day 30 in our systematic analysis at a nationwide level from a mandatory administrative database, including centers where patients may be transferred after the TAVR procedure.
Limitations A main limitation of our work is inherent to the retrospective, observational nature of the study and its potential biases. Furthermore, the study was based on administrative data, with limitations inherent to such methodology. The PMSI database contains diagnoses coded using ICD-10, which are obtained at hospital discharge and are the physician's responsibility. Data were not systematically externally checked, and this could have caused information bias. However, the large scale of the database is likely to partly compensate this bias and, as coding of complications is linked to reimbursement and is regularly controlled, it is expected to be of good quality. Our large population of patients treated with the TAVR procedure likely represents a heterogeneous group of patients admitted with various kinds of illnesses and severities.
The nonrandomized design of the analysis leaves a risk of residual confounding factors. We have been able to estimate the EuroSCORE II, which in our cohort showed a satisfying correlation with early clinical outcomes. Moreover, the Charlson comorbidity index and Frailty index were used as risk predictors of allcause death over a longer term. Our analysis was restricted to the variables in the database, which meant that characteristics such as mean gradient, valve area, calcifications, and paravalvular leak were not available for analysis. We had information for diagnoses of left or right bundle branch block or atrioventricular block on ICD-10 codes, but precise QRS durations in ms on surface ECG and results obtained during electrophysiological study were not available. Left anterior fascicular block was not included in our analysis because it is generally not reliably indicated in administrative medical records.
Remerciements Dr. Iman Aouidad ,  Dr. Astrid Blom ,  Dr. Pauline Bonnet ,  Dr. Sebastien Beaune ,  Dr. Felicie Costantino ,  Lise Charmet Delaoutre ,  Josephine Courjol ,  Pr Pascal Crenn ,  Dr. Marine Delaroche ,  Dr. Elisa Funck Brentano ,  Catherine Jehanno ,  Dr. Clemence Gallon ,  Sabrina Gasson ,  Pr Elyanne Gault ,  Dr. Lara Gonzalez ,  Dr. Christine Longvert ,  Dr. Anne sophie Lot ,  Caroline Meuro ,  Dr. Sandrine Ngo ,  Dr. Ilaria Padovano ,  Dr. Marianne Rameix ,  Dr. Anissa Roger ,  Dr. Francois Vidal ,  Dr. Valérie Sivadon-Tardy ,  Amelie Zérelli.
Background. -Tandem basilar artery occlusions (tBAO) are defined as concomitant basilar artery and extracranial dominant vertebral artery occlusions. The prognosis of such tBAO treated by mechanical thrombectomy (MT) has been scantly reported. The purpose of our study was to compare the safety and effectiveness of MT for patients with tBAO compared to those with non-tandem basilar artery occlusions (ntBAO). Patients and methods. -Retrospective analysis of a database of patients who underwent MT at two academic centres. All patients treated for BAO were retrieved. Patients with tBAO, defined as a concomitant BAO and extracranial vertebral artery (VA) occlusion or severe stenosis ≥70% (V1 or proximal V2 segment) were compared with patients with ntBAO. Results. -A total of 15 patients with tBAO and 74 patients with ntBAO were enrolled.