dataesr/scientific-paragraphs-categorization huggingface dataset:
Despite these limitations, we believe that the false-positive rate is likely to be low, as demonstrated by known associations detected by our analysis (i. e. , drugs listed by crediblemeds Ò such as haloperidol), which can be considered as positive controls and support the accuracy of the method. Our study carries important clinical, research and regulatory implications. From a clinical standpoint, antipsychotics are the most frequently reported agents, especially in Germany. Notably, amisulpride, aripiprazole, haloperidol, olanzapine and risperidone were the only drugs associated with SDRs in all databases. This consistency across all SRSs is indicative of a known pro-arrhythmic risk and may be also related to the considerable and increasing population exposure over years  [11]. From a research standpoint, multiple database analyses are only rarely exploited for signal detection: we believe that the use of different SRSs represents an added value in the current era of drug safety research, where several consortia have been created to fully assess drug-related risks in the post-marketing setting.
As compared with post-marketing safety studies on healthcare databases, where multiple databases are pooled to increase statistical power, spontaneous reporting databases should not be combined, but analyzed separately to maintain country-specific differences. Further research is now warranted to test the overall signal detection performance of national SRSs when studying rare events with newly approved drugs (especially in terms of time to first detection), for which data aggregation is theoretically advisable considering the centralized approval of the majority of current medicinal products. From a regulatory standpoint, the remarkable proportion of torsadogenic reports recorded for antipsychotics in Germany deserves consideration by national authorities and may partially reflect their widespread prescriptions in nursing home residents with dementia, especially for firstgeneration agents with sedative properties  [22, 23].
2. The German SRS (2005-2010) collects all adverse events associated with all licensed medicinal products on the market in Germany; it is operated by the Federal Institute for Drugs and Medical Devices (German name, BfArM), which usually accepts reports from healthcare professionals only. However, reports submitted by pharmaceutical industries have been recorded since 2008. The database is accessible for research purposes, provided that a formal application with a defined subset of variables is presented to the Agency. Causality of drug-induced adverse events is only suspected and not validated. Data coverage starts in 1978, although full electronic records are only available from 2005 onwards. Free-text search strategy cannot be performed. Manual codification of drugs was specifically imple- mented to systematically codify active substances into V level ATC codes.
3. The Italian SRS (1969-2010) is based on the Rete Nazionale di Farmacovigilanza (RNF), a network involv- Authorization Holder is notified to avoid duplicate sending to Eudravig- ilance. The drug manufacturer has the obligation to send reports from the literature of serious adverse drug reaction (ADR) occurring in Italy to the RNF, attaching the relevant article. Reports coming from the literature have not been considered in the analyses. Codification of adverse reactions has been performed through MedDRA Ò since 2005, whereas for the 1969-2004 period, the World Health Organization Adverse Reaction Terminology (WHO- ART) terminology was used; a bridge is required to search the database with both terminologies. ing the Italian Medicines Agency (AIFA), Italian regions, local health units, hospitals, Institute of Research and Care and drug industries.
5 ml of EDTA-blood were stained with anti-human-Glycophorin A mAb coupled to FITC (eBiosciences), washed in PBS, fixed in 0. 2% PFA and analysed using a LSR Fortessa cytometer (Plateforme de cytometrie en flux CYPS, La Pitie-Salpetriere, Paris). Analyses were performed using the FlowJo software 7. 6. 3. Statistical analyses. The sizes and areas of P. falciparum schizonts at days 5 and 7 were compared using the Mann-Whitney U-test (GraphPad Prism software).
Acknowledgments The authors are deeply grateful to  Prof. Katharina Ribbeck  for insightful discussions and for supporting this study, conception to completion, in her laboratory. The authors also thank  Dr. Gulden Camci-Unal  for valuable discussions regarding methacrylation of mucin and  Ms. Alice Galais  for generating the chemical structures in Supplementary Figure 3. Finally, the authors gratefully acknowledge the  Research Science Institute  for support to C. V. D and the  Marie Curie International Outgoing Fellowship  ( BIOMUC ) for support to T. C.
Real-time qPCR Total RNA was isolated using TRI reagent (Sigma) according to the manufacturer's instructions. Reverse transcription was performed using oligo(dT) primer and 1μg of total RNA in a final volume of 20 μL with the RevertAid First Strand cDNA Synthesis Kit (Thermo scientific). Real time qPCR was performed using the FastStart Essential DNA green Master kit (Roche) on a lightcycler Instrument equipped with the SW 1. 1 data analysis software (Roche). Analyses were done in triplicate. Data were normalized using HPRT as housekeeping gene. Primer sequences are: Reg3α forward: 5'-TGGATTGGGCTCCATGACCC-3'OH, Reg3α reverse: 5'-TTCGGGATGTTTGCTGTCTG-3'OH, HPRT forward: 5'-AGGACCTCTCGAAGTGT-3'OH, HPRT reverse: 5'-TCAAATCCCTGAAGTACTCAT-3'OH.
Protein carbonylation Carbonyl groups of 1 μg of DOC insoluble and 10 μg of DOC soluble proteins were derivatized to 2, 4-dinitrophenylhydrozone (DNP) by reaction with 2,4-dinitrophenylhydrazine in solution in 2N HCl, incubated 30 min in the dark at room temperature before being precipitated by addition of an equal volume of 20% trichloroacetic acid. Protein pellets were washed four times with 1 mL of ethanol/ethyl acetate (1:1), and resuspended in SDS loading buffer. One half of each sample was analyzed by Western blot using a rabbit anti-DNP antibody while the other half was resolved on a 10% acrylamide gel for Coomassie blue staining. Amount of carbonylated and total proteins were determined by densitometry using the Image J image processing and analyzing software; results were presented as the ratio of carbonylated on total proteins.
Acknowledgments The authors would like to thank  Dr Raphael Boisgard  ( CEA, University Paris Sud, Orsay, France ) for providing FITC-coupled Reg3α protein;  René Duchateau  and  Dr Christelle Martin  ( CNRS-SEAT, Villejuif, France ) for animal care assistance, and  Mylène Sebagh  ( UMR-S 785 INSERM/Université Paris Sud, AP-HP Hôpital Paul Brousse, Laboratoire Anatomie Pathologie, Villejuif, France ) for pathologist assistance.
cellulosum So ce56 and Arh1 from S. pombe were used as electron donor for SynFdx, slightly higher rates compared to the spinach system were observed. However, the hybrid redox system containing ferredoxin from Synechocystis and FNR from C. reinhardtii yielded eight to eleven times (depending on component ratio) higher conversion rates in vitro, compared with the values calculated for spinach Fdx/FNR. Additionally, kinetic studies of the epoxidation of epothilone D were performed using the ratio 1:20:3 for the EpoK/SynFdx/FNR system. A v max value of 9. 03 ± 0. 17 nmol product min -1 nmol -1 EpoK and K 1/2 = 1. 73 ± 0. 05 μM were obtained by using the Hill-equation (Fig. 3 ). The replotted Lineweaver-Burk plot of the data (Fig. 3  inset) also showed the similar values of v max and K m of 10.
Bioinformatics. Pairwise protein sequence alignments were performed using the Needlemann-Wunsch algorithm (EMBL-EBI: Needle (EMBOSS)). Protein sequences were taken from NCBI protein database (UniProtKB). Heterologous expression and purification of P450s. E. coli BL21 (DE3) cells were transformed with the pCWori_EpoK plasmid encoding the C-terminal hexahistidine-tagged EpoK from S. cellulosum So ce90. An overnight culture was prepared from a single colony and was grown at 37 °C in lysogeny broth (LB) medium (10 g tryptone, 5 g yeast extract and 10 g NaCl per liter H 2 O) containing 100 μg ml -1 ampicillin. For the heterologous expression of EpoK, a main culture of 500 ml terrific broth (TB) medium (24 g yeast extract, 12 g peptone, 4 ml glycerol, 2. 31 g K 2 HPO 4 and 12. 54 g KH 2 PO 4 per liter H 2 O) containing 100 μg/ml ampicillin was inoculated with 5 ml of the overnight culture and grown at 37 °C.
The effect of CAIX inhibitors on growth and invasion of tumor explants To assess the effects of CAIX inhibition in actual tumor tissue, ex vivo human breast tumor explants from pre-treatment fresh core needle biopsies were examined. A representative assay using FC9403A is shown in Figure  3A (A-D ), after 5 days of culture, and demonstrates clear invasion in both the control (A) and 10 μM (B) treated explants, while higher concentrations of 30 (C) and 100 μM (D) prevented invasion. Figure  3B  illustrates pooled data from 26 separate biopsy specimens (explant number = 214 -177 per time point) after growth in collagen for 15 days with invasion assessed by increased area. Although approximately 50% of explants were invasive by Day 5, the percentage increase in invasion was significantly increased by Day 10.
Wounding/invasion assay Cells (MDA-MB-231 or SKOV3 (5 × 10 5 /well)) were grown in 6-well plates until confluent. After wounding with a sterile tip, media containing 0. 2% serum and the drug of interest were added. Invasion/migration of cells was calculated by comparison of the scratch at time '0′ and after 24 or 48 hours. The extent of migration of the SKOV3 cells was determined by analyzing the percentage of closed wound area, measured using DatInf Measure setup Wizard software.
Complete and accurate information sent to the SPS will help the evaluators to investigate if there is a signal of association between a drug and ADRs. Therefore, the aim of this study was to assess the completeness of ADRs reports in the SAERS. Methods. The study was conducted on the reports entered into the SAERS's electronic database at the SFDA. The SAERS receives the ADRs reports from all regions in Saudi Arabia, as well as from international manufacturers. A confidentiality agreement between the investigators and the SFDA was agreed. The investigators had no access to the patients' and reporters' names or contact and company information, while reviewing and analyzing the reports in the SAERS database. This study was approved by the research committee at the Medication Safety Research Chair at King Saud University, Riyadh.
Study design. This was a cross-sectional study that included all reports to the SPS between December 2009 and June 2012. The pharmacovigilance center at the SFDA accepts all reporting forms (forms made by the SFDA or by hospitals) including the 'ADRs for Health Professional form', the 'ADRs for Consumer form', and the Council for International Organizations of Medical Sciences' (CIOMS) form'. The latter form is used by pharmaceutical companies. These reporting forms have the same fields; however, the ADRs for the consumer form are available in the Arabic language. The SAERS electronic data from the SAERS database were exported to the IBM SPSS Statistics for Windows version 20. 0 (IBM Corp, Armonk, NY, USA), and then combined according to the SFDA identification number for the statistical analysis and evaluation of the different variables.
Statistical analyses. Descriptive statistics for all elements of the SAERS were calculated. The age group of the reports were determined by computing the 'age at onset of action' with 'the date of birth'. To determine the most reported drugs and event type each year, the statistics were carried out according to the 'event onset of action date' of each report. The data was analyzed using the IBM SPSS Statistics for Windows version 20. 0 (IBM Corp, Armonk, NY, USA) except data related to the frequency of the event, age group, and type of institution were analyzed by using the Statistical Analysis Software (SAS), version 9. 2 (SAS Institute Inc. , Cary, NC, USA) Results. The total number of reports received by the pharmacovigilance center and available at SAERS between December 2009 and June 2012, were 14,783.
The patient demographic data were filled out in 38. 3% of reports, whereas the event outcome information was available in 88. 6% of the reports (Figure  1 ). The gender was completed in 13,356 (90. 3%) reports. Furthermore, the age of the patients was completed in 8,712 (58. 9%) reports and in 3,862 (26. 1%) reports, 'date of birth' was completed. We had to create a variable that combined the age and the date of birth fields and the total number of completed reports was 12,574 (85%). Additionally, height was completed in 4,184 (28. 3%) reports, and weight in 3,115 (21. 1%), while the 'health institution' field was completed in only 3,811 (25. 8%) reports. The reports in the study included 48,417 drugs. Some drugs occurred in more than one report. The mean was 3 drugs per report, with a range of 1-22 drug(s) per report.
However, only 15% of the reports filled up the professions. Assessing the quality of SAERS. Thirty random reports were selected by simple sampling from the SAERS database to assess the quality of information describing the adverse events. Based on the aforementioned criteria in the methods section, the SAERS reports were of good quality and the required information regarding the adverse event was mentioned, was also of good quality. Perform descriptive statistics for SAERS elements. Most of the patients were female; there were 7,364 (55. 1%) females compared with 5,992 (44. 9%) males. As expected, reported ADRs included more elderly people; as 5,888 (55. 8%) of the reports were on patients aged above 60 years old, while only 1,436 (13. 6%) reports were on patients aged 20 years old or younger.
Furthermore, the SAERS reports show a good quality related to the adequacy of information describing the adverse event. However, the method of assessing the quality of these reports is not well-defined and there is no global standard for it. Therefore, there is a need for a well-designed structure in evaluating the quality of such reports. In contrast to the SAERS, the Adverse Drug Events Spontaneous Triggered Event Reporting (ASTER) pilot study  18  has 100% completed information related to patient demographics. However, the ASTER study has more advantages since the data were received from a triggered electronic health record, which usually contains most of the required data in detail. In addition, our results were similar to a study by Alshammari et al  7  who investigated the quality of the Food and Drug Administration (FDA) SAER system and found that the FDA database is of good quality.
Nevertheless, it is recommended that awareness is increased on the importance of completing all the patient demographic information to help understand the roles of age, gender, weight, and other information in the occurrence of a specific event. The detailed information related to the reporter was completed least, and only the type of reporter was obtained. This was due to limited access to SAERS due to confidentiality issues. Most reported events were serious, though the seriousness of the types of the events was not clearly described. The French study  9  revealed that approximately 44% of the events were serious, which is lower than our results. This could be due to the French database  9  having more reports from HCPs who usually reported all types of events (serious and non-serious). A Danish study 8 evaluated the reports submitted to the Danish reporting system and found that approximately 52% of the reports were serious.
Implications and recommendations. The information in the database is starting to increase when we compare the starting years and the last year in the study and this could help in the future to assess the signal between a specific event with a specific drug; however, we should keep in mind that some drugs and/or events would have few reports. It is recommended that the report date be added to the reporting forms, which will be helpful for further assessment and evaluation. There are some considerations that the pharmacovigilance department at the SFDA should consider to enhance the data quality by avoiding the use of manual drug entry to prevent spelling mistakes and false duplicated drug frequencies, as well as to stick to the drug name codes and to add the uncoded drug names to the system.
Factorial design The factorial approach was performed for MS crosslinked with GL in order to optimize geometric size, for which determination is faster than aerodynamic size in the formulation development stage. This experimental design included four independent variables (x 1 to x 4 ) and two coded levels (À1, +1) (Table  1 ). The values at each level were chosen considering acceptable domains for each variable and according to therapeutic approach and published works  [19, 20, 32, 33]. Programs developed by the authors with GNU Octave software  [34]  were used to solve the polynomial multilinear model: The response D (dependent variable) corresponded to the mean diameter of the MS from the volume distribution. This model was applied to evaluate the effects and interactions of the variables.
Particle size analysis MS were dispersed in purified water, sonicated for 10 min and analyzed using laser light diffraction (Microtrac Ò X100 particle size analyzer) as previously described  [35]. Three measurements were carried out for each sample and particle size expressed as the mean diameter ± SD of the volume distribution (D v ) was calculated using the Microtrac Particle Size Analyzer application program (version 9. 0 g).
Acknowledgments The authors thank  FCT  ( Fundação para a Ciência e a Tecnologia, Portugal ) for the financial support through the grant  SFRH/BD/80307/2011. DTA/TGA, XRD and ATR-FTIR analyses were performed at the  University of Poitiers ,  Pôle Commun de Mesures Physico -chimiques platform. Spray-drying experiments were carried out in Biocydex, Poitiers. The authors thank  Patrice Gobin  and  Christophe Adier  for their technical assistance in HPLC measurements.
Purpose: This study was performed to assess the reproducibility of identifying the sella turcica landmark in a threedimensional (3D) model by using a new sella-specific landmark reference system. Materials and Methods: Thirty-two cone-beam computed tomographic scans (3D Accuitomo ® 170, J. Morita, Kyoto, Japan) were retrospectively collected. The 3D data were exported into the Digital Imaging and Communications in Medicine standard and then imported into the Maxilim ® software (Medicim NV, Sint-Niklaas, Belgium) to create 3D surface models. Five observers identified four osseous landmarks in order to create the reference frame and then identified two sella landmarks. The x, y, and z coordinates of each landmark were exported. The observations were repeated after four weeks. Statistical analysis was performed using the multiple paired t-test with Bonferroni correction (intraobserver precision: p⁄0.
Materials and Methods The study protocol (reference number: ML6960, BE 322201010078) was approved by the Medical Ethics Committee of the University Hospitals Leuven. The authors have read the Helsinki Declaration and have followed its guidelines in this investigation. Thirty-two patients (11 males and 21 females, age range 8. 8-76. 7 years, mean age 26. 0±21. 6 years) were retrospectively selected from the hospital database. The selection criteria were: (1) patients with CBCT images, (2) the presence of the sella turcica in the images, (3) no significant pathology of the maxillofacial region, (4) no significant facial asymmetry, and (5) no significant anatomical variation in the sella turcica and sphenoidal regions. The CBCT scans of each patient were taken with a 3D Accuitomo ® 170 device (J.
Morita, Kyoto, Japan) with a minimum field of view of 140×100 mm (90 kVp, 154 mAs, voxel size 0. 25 mm. ) The CBCT data were exported from the i-Dixel ® software (J. Morita, Kyoto, Japan) into the Digital Imaging and Communications in Medicine format and then imported into the Maxilim ® software (Medicim NV, Sint-Niklaas, Belgium). Three-dimensional surface models for all subjects were created using the full CBCT volume with 0. 5-mm voxel subsampling. The threshold value was set between 276 and 476 in order to segment the hard tissues for the 3D models. The models were then saved and randomized.
Reference frame A reference system was created in the Maxilim ® software in order to identify the geometric center or midpoint of the sella turcica. The reference frame was composed of six landmarks (four operator-indicated landmarks and two software-calculated landmarks) and two sella landmarks, which were indicated on two distinct vertical planes created from the reference system (Table  1 ) (Fig. 1 ). of experience, respectively, and one maxillofacial surgeon with 20 years of experience) were initially introduced to the technique through an instruction and calibration session that allowed the observers to understand the definitions of the landmarks and to become familiar with the software. During each observation session, an observer identified six landmarks (Table  1 ). The x, y, and z coordinates of each landmark were exported to Microsoft Excel files.
One potential reason for this is of the possibility that the landmarks and bony structures were more difficult to visualize in the CBCT scans of some patients, and moreover, that image noise was more of a problem in some CBCTs. The selection of the devices used to perform CBCT may also be a key factor in performing 3D cephalometry, as the choice of imaging device may affect the image quality and the quality of the 3D computed surface model. In the present study, the data were retrospectively collected and only one type of device was used. The CBCT data were tested for compatibility with the Maxilim ® software. The Maxilim ® software showed a minor limitation in the segmentation of 3D surface models; namely, the software does not allow the operator to reduce any noise or artifacts in the image.
Intraobserver precision was slightly better than interobserver precision. This trend was expected, as differences between examiners are a factor that may influence the results of observational studies. Differences in the observers' backgrounds, their familiarity with the software, and their ability to identify landmarks according to the definitions provided all might affect interobserver precision. A calibration session was performed in order to minimize this effect as much as possible. In this study, two of the observers (observers 1 and 2) had more experience in using the Maxilim ® software before the observations. This led to a visible difference in the results. There were significant differences in intraobserver precision among observers for some landmarks (ACP-R, ACP-L, APT-R, and APT-L), and it was found that two observers (observers 1 and 2) were able to identify the landmarks more precisely.
The study population comprised elderly patients who were hospitalized in the five trauma units of the hospital during the period April to August 2014. The population also included a census of patients hospitalized with oral and maxillofacial trauma. According to Brazil's National Health Policy for the Elderly, an older person is anyone 60 years of age or older  [10]. Data collection involved two stages. First, secondary information was obtained from the hospital information system using daily data, organized by unit and bed of the five hospitalization units. This census provided the number of all patients admitted to the hospital care system. After this information (patient, age, type of trauma) was transcribed, a questionnaire was used to obtain data on sex, race, marital status, education, origin (capital or other municipalities in the State of Ceará), income, presence of systemic comorbidities, use of medication, smoking and alcohol consumption, and specific information, such as oral and maxillofacial trauma etiology, and the type of prehospital care (formal or informal).