dataesr/scientific-paragraphs-categorization huggingface dataset:
3 to 3. 0 TU/cell). On the following day, microphotographs of GFP autofluorescence were taken to confirm that all cultures had been infected at comparable levels (data not shown). As in the experiment described in Figure  3 , cell samples were treated with KCl to induce CGRP secretion. Then neurons were harvested for Western blots to assess cleavage of SNARE proteins. Results shown in Figure  5A  indicate that all BoNT LC were able to inhibit CGRP release in a vector dose-dependent manner, although they did so with variable potencies. Thus, the vector expressing BoNT-F LC produced a greater inhibition of CGRP release than those expressing BoNT-B or -D LC, which also cleave VAMP2. Indeed, at a MOI of 1 TU/cell BoNT-F LC inhibits CGRP release as efficiently as BoNT-B LC at 3 TU/cell and is more potent than BoNT-D LC at 3 TU/cell.
Regarding the BoNTs that cleave SNAP25, no significative differences were evident between BoNT-A, BoNT-C and BoNT-E LCs in inhibiting CGRP secretion. It must be noted however that BoNT-C LC cleaves STX in addition to SNAP25, and this could also contribute to inhibition of neurosecretion  [5, 6]. In mock-infected embryonic rat sensory neurons or in neurons infected with a vector expressing Luc, no inhibition of CGRP release took place (data not shown). It is noteworthy that inhibition of CGRP release can be detected in some cases in neurons In a second experiment, cultured rat embryonic DRG neurons were infected with vectors expressing the LC of BoNT-A, -B, -C, -D, -E, -F, or Luc at increasing MOI (from 0. 3 to 3. 0 TU/cell). On the following day, microphotographs of GFP autofluorescence were taken to confirm that all cultures had been infected at comparable levels (data not shown).
Plasmids Containing the LC of BoNTs A family of pUC57 plasmids carrying the sequences of the light chains of BoNT-A, -B, -C, -D, -E, and -F, as described in GeneBank [accession numbers of BoNT-A LC: DL193752. 1; BoNT-B LC: KF878257. 1; BoNT-C LC: X53751. 1; BoNT-D LC: AB012112; BoNT-E LC: EF028403. 1; BoNT-F LC: GU213203. 1] has been ordered (GenScript). An additional pUC57 plasmid, carrying the sequence of GFP-BoNT-A LC fused protein was also constructed. Since the BoNT genes are of bacterial origin, the sequences carried by the pUC57 plasmids were modified to take into account the codon usage of mammalian cells, thus optimizing translation in these cells but without modifying the translated product. In addition all these sequences were engineered to contain a NheI site at the 5 end and a NotI site at the 3 end to facilitate subcloning into amplicon plasmids.
Funding: This research was funded by  Wings for Life-Spinal Cord Research Foundation  grant  WFL-FR-07/17 -N • 154 , by  EU ERANET-Neuron  grant  N • ANR-16-NEU3-003 , attributed to the  ELPIS program , by the  French Agence National pour la Recherche (ANR)  grant  N • ANR-10-IBHU-0006 , attributed to the  HandiMedEx program , and by a  SATT  Paris-Saclay 2016 maturation grant.
ACKNOWLEDGMENTS This work was partially supported by research grants from  Luxembourg Cancer Foundation and Télévie  to AM and from  Oryx GmbH  to AM, AA, and JR. Oryx GmbH had no involvement in the writing of the manuscript and in the decision to submit it for publication. We would like to thank  Clemens Bretscher  for art work and  Caroline Hadley  (INLEXIO), for critical reading and editing.
The MicroScan system is a rapid technology for microbial identification able to provide results after 4 h of inoculation  [15]. Only available for yeast identification, this method relies on enzymatic reactions in a panel. The enzyme activities of each isolate are determined by colour changes in the chromogenic substrates (or a pH indicator). The biochemical reactions generate numerical profiles, which are then compared with a numerical database. In recent years, Mass Spectrometry (MS) using MALDI-TOF MS technology has been increasingly used as a tool for microbiological identification due to its high performance and less time required when compared with conventional methods  [16]. Our aim was to compare the performance of Micro-Scan with that of MALDI-TOF MS for yeast identification. This study was conducted on a large collection of clinical isolates collected prospectively at the San Ignacio Hospital, Bogota, Colombia.
In addition, the performances of this phenotypic system are intimately dependent on regular updates of the database. Since MicroScan is not capable of identifying Geotrichum spp. (at the species level), we recorded those isolate identifications as erroneous. In addition, cryptic or recently emerging species such as C. auris, C. intermedia C. metapsilosis, C. nivariensis, C. orthopsilosis, C. gattii and S. suaveolens, which are not yet present in the MicroScan database version 4. 11. 1020. 1 cannot be readily identified. MALDI-TOF MS systems have recently been developed and implemented in diagnostic microbiology laboratories for bacterial and fungal identification due to their efficacy, rapidity and minimum hands-on time. This technology, as highlighted here, provides valid results for most yeast species (84-99%).
However, optimal results depend on the robustness of the system libraries  [18, 19]. For those reasons, the accuracy of the MALDI-TOF MS System is modifying the way in which yeast identification is being performed, surpassing the conventional techniques. In this study, MALDI-TOF MS could correctly identify 98. 9 of the strains analysed. The 5 errors were due to a misidentification of C. metapsilosis and the lack of identification of Trichosporon faecale and Saprochaete suaveolens even though they are present in the Biotyper database. We believe that the error was possibly due to the frequent difficulty in protein extraction for these species. In the case of Saprochaete suaveolens the database is not robust thus leading to erroneous results. A solution to the identification of these microorganisms is the creation or improvement of libraries  [20].
MicroScan WalkAway system The MicroScan system for yeast identification consists of a 96-well microdilution plate with 27 dehydrated chromogenic substrates. The enzyme activity of each isolate is determined by colour change. Isolates were previously grown on Sabouraud dextrose agar (SDA) at 30 °C for 24-36 h. Suspensions were prepared and calibrated against the MicroScan turbidity standard, and the panel was incubated aerobically for 4 h at 37 °C. Biochemical reactions generate numerical profiles that are compared with a database to identify organisms  [15]. Urease assimilation and growth on canavanine-glycine-bromothymol blue agar confirmed the identification for Cryptococcus isolates.
Each sample was tested in duplicate. Only the spot returning the highest probability score of identification was considered  [24]. The protein mass spectra was analysed using the Flex Control software and the MALDI Biotyper version 3. 1 7311 reference spectra (main spectra) (Bruker Daltonics, Bremen, Germany). MALDI-TOF MS results were then compared and a score was obtained according to the manufacturer's technical specifications, as follows: correct genus and species identification (≥2. 0), correct genus identification (1. 7-2. 0), and no reliable identification (< 1. 7)  [25]. The 498 clinical isolates was a score above 2.
Molecular identification Molecular identification of discrepant isolate results between both methods was subjected to molecular identification by amplification and sequencing of the ITS rDNA regions without prior DNA extraction step (colony PCR)  [26]. Amplification of the ITS rDNA was achieved using the universal primers ITS1 (TCCGTAGGT-GAACCTGCGG) and ITS4 (TCCTCCGCTTATTGA-TATGC)  [27]. Nucleotide sequences were assembled using the Seq Scape software (Applied Biosystems, Foster City, CA, USA. ) and compared with the GenBank database using the BLAST algorithm or with the MycoBank database. For some isolates, identification was further confirmed by amplification of the D1-D2 region of the 28S rDNA using the primers NL1 (GCATATCAATAAGCG-GAGGAAAAG) and NL4 (GGTCCGTGTTTCAA-GACGG)  [27]. A similarity ≥98% between the unknown sequence and the closest matching sequence from the reference database was used as the criterion to identify an isolate to the species level.
Source of data We used data from the Control and Burden of Asthma and Rhinitis (ICAR) study (PTDC/SAU-SAP/119192/2010), a nationwide population-based observational cross-sectional study conducted in Portugal (ClinicalTrials. gov: NCT01771120). The study was approved by a hospital ethics committee (Comissão de Ética do Hospital São João EPE, on October 17, 2011) and by the national data protection committee (no. 12372/2011). All participants signed the consent form. Methods regarding sample size calculations, participants, and data collection in the ICAR study are described in the "Methods" section in this article's Online Repository at www. jaci-inpractice. org. Data collection included lung function and exhaled nitric oxide, skin prick tests, a structured clinical assessment, and standardized questionnaires.
Nevertheless, the presentation of the results as a continuum score before dichotomization using a cutoff is advisable. The use of the A2 score and the GA2LEN score may contribute to reducing the inconsistencies of asthma definitions across studies and surveys and have the potential to be used in clinical settings for screening/triage of asthma, where they may contribute toward identifying the best candidates to be referred for diagnostic workup. A. S. is supported by a PhD grant (grant no. PD/BD/113665/2015), financed by the European Social Fund and the national funds of the Ministério da Ciência, Tecnologia e Ensino Superior through the Fundação para a Ciência e Tecnologia, I. P. , PhD program (reference no. PD/0003/2013: Doctoral Program in Clinical and Health Services Research). The data collection was part of a project funded by the Fundação para a Ciência e Tecnologia, I.
METHODS This section describes in detail the methods of the ICAR study. The ICAR was a nationwide population-based observational cross-sectional study. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, consistent with good clinical practice and the applicable regulatory requirements, and was approved by a hospital ethics committee (Comissão de Ética do Hospital São João EPE, on October 17, 2011) and by the national data protection committee (no. 12372/2011). The study protocol containing standard operational procedures was registered in ClinicalTrials. gov (NCT01771120). All participants signed the consent form.
Participants and data collection In the ICAR study, all subjects who have been included in the INAsma (Inquérito Nacional sobre Asma) study  E3,E4  and who have expressed their willingness to participate in a clinical assessment were eligible along with their family members. Furthermore, local media and posters were used to disseminate the study and invite participants. Persons who did not understand spoken Portuguese and who had cognitive or physical conditions that could hamper their participation in the study were excluded. Data were collected between October 30, 2012, and July 12, 2014, in 2 allergy clinics (Lisbon and Porto) or by using a mobile diagnostic unit, on the basis of the participants' geographical proximity. Participants were screened by telephonic interview into 1 of the 4 groups.
A total of 858 participants, either with asthma and/ or rhinitis or with no previous history of respiratory symptoms or diseases (aged between 3 and 89 years), were included from 90 Portuguese cities. Data collection comprised anthropometric measurements, lung function and exhaled nitric oxide tests, skin prick tests, a structured clinical assessment, and standardized questionnaires. Anthropometric measurements of height, weight, and waist/hip circumference followed the procedures manual of the National Health and Nutrition Examination Survey. E5  Lung function tests included spirometry with postbronchodilator reversibility (EasyOne Pro, ndd, Zurich, Switzerland, and Jaeger IOS, CareFusion, San Diego, Calif), carbon monoxide in exhaled air (SmokeCheck, Micro Medical, Kent, UK), and exhaled nitric oxide (NIOX Mino, Aerocrine AB, Solna, Sweden), and were done according to standardized methods.
ACKNOWLEDGMENTS This study received support from IRD and University of Montpellier intra-mural funding provisions. We thank the EID M editerran ee in Montpellier for kindly providing the Ae. albopictus strain, Antoine Nicot for the Cx. pipiens strain, and Vectôpole (IRD) for the An. gambiae, An. coluzzii, An. aegypti, and Cx. quinquefasciatus strains. The invaluable assistance of Carole Ginibre in rearing the mosquito laboratory strains is warmly acknowledged as well as the constructive criticism of two referees. The authors declare that they have no competing interests.
Background: Supplemental oxygen therapy is widely used in hospitals and in the home for chronic care. However, there are several fundamental problems with the application of this therapy such that patients are often exposed to arterial oxygen concentrations outside of the intended target range. This paper reports volume-averaged tracheal oxygen concentration measurements (FtO2) from in vitro experiments conducted using a physiologically realistic upper airway model. The goal is to provide data to inform a detailed discussion of the delivered oxygen dose. Methods: A baseline FtO2 dataset using a standard, straight adult nasal cannula was established by varying tidal volume (V t ), breathing frequency (f), and continuous oxygen flow rate (Q O2 ) between the following levels to create a factorial design: V t = 500, 640, or 800 ml; f = 12, 17, or 22 min -1 ; Q O2 = 2, 4, or 6 l/min.
In vitro model The general in vitro methodology is described by Chen et al. [23, 24]. Briefly, with reference to Fig. 1 , a realistic adult nose-throat airway replica was connected to a lung simulator (ASL 5000 Breathing Simulator, IngMar Medical USA) used to simulate tidal breathing. A photo of the experimental setup is also shown in Fig. 1. The volume of the chamber of the test lung was recorded during simulated breathing at a sampling frequency of 512 Hz using the ASL 5000 software. The airway replica was developed previously using medical images from an adult volunteer and 3D-printing techniques  [31]. The replica outlet, corresponding to the entrance to the trachea, was connected to the lung simulator breathing circuit with 22 mm internal diameter tubing. The total internal volume of this tubing was 135 cm 3 , representative of the conducting airway volume from the trachea to the gas exchange regions of the lungs for an average adult with 3 L functional residual capacity.
Continuous flows of oxygen were delivered to the replica via nasal cannula (or other patient interfaces as indicated) from a regulated compressed oxygen cylinder through a calibrated mass flow controller (MCMC-Series Mass Flow Controller, Alicat, USA). Gas was sampled at the exit of the replica (representing the trachea) and oxygen concentrations were measured using a laser diode analyzer (GA-200, iWorx, USA) at a frequency of 34. 88 Hz. Real-time oxygen concentrations from the analyzer and volume vs. time data from the lung simulator were streamed via virtual instrument software architecture (VISA) serial and TCP/IP connection ports, respectively, to a program written in LabVIEW (National Instruments, USA) for collection and synchronization. Total gas flows at each point in time were then calculated using forward differences from the volume data.
FtO2 for each test was calculated as the average of five consecutive breaths after a steady state in expiratory oxygen concentration was observed (after at least 50 breaths). Previous testing of both continuous and pulsed oxygen delivery through realistic adult nose-throat airway replicas has been reported by Chen et al. [23]  In that work, tests were repeated in 15 replicas, and FtO2 data were presented as average values along with standard deviations between replicas. These tests provide a subset of data through which the influence of nasal airway geometry on FtO2 may be explored. For further testing described herein, a single replica has been selected, to allow a wider range of breathing parameters to be explored while limiting the total number of experimental repetitions. Fig. 2  displays FtO2 values measured for the replica selected for the present study (labeled MRI5) compared with average values for the 15 replicas studied by Chen et al.
In vitro dosing experiments The apparatus and techniques were applied to 105 separate in vitro dosing experiments consisting of a baseline set plus several other sets to investigate fundamental oxygen therapy variables. Thus, the purpose of the baseline dataset is to provide a basis of comparison for the other oxygen therapy variables considered in a parametric methodology; such that we report the oxygen dose first for the baseline cases and then as more or less from the baseline for the single variable that was modified. Additional file 1: Table  S1  provides a list of each experiment's parameters. A description of the experiment sets follows.
Baseline dataset The baseline dataset was established using a standard, straight adult nasal cannula (Model 1103; Hudson RCI, USA) patient interface and by varying tidal volume (V t ), breathing frequency (f), and oxygen flow rate (Q O2 ) between the levels specified below in a factorial design: V t = 500, 640, or 800 ml; f = 12, 17, or 22 min -1 ; Q O2 = 2, 4, or 6 l/min. The inspiratory/expiratory (i/e) ratio was held constant at approximately 0. 5 to match inhaled and exhaled volumes in user-defined breaths simulated by the ASL 5000 instrument (i/e deviated slightly from 0. 5 as indicated in Additional file 1: Table  S1  with no end-expiratory pause nor end-inspiratory pause in the simulated breaths). Inspiratory and expiratory phases of the breath are modeled as half-sine waves.
Influence of deviations from characteristic breathing pattern Three deviations from the characteristic baseline breathing pattern were performed i) for an inspiratory/expiratory ratio i/e = 1. 0, ii) an i/e ratio of 0. 5, and with the addition of an end-expiratory pause (EEP) occupying 20% of the total breath time, and iii) with an i/e ratio of 0. 5, and with the addition of an end-inspiratory pause (EIP) occupying 10% of the total breath time. For each type of deviation from the characteristic breathing pattern, a subset of tests were repeated from the baseline dataset. The repeated combinations of tidal volume and breathing pattern were V t = 500 ml and f = 12 min -1 , V t = 640 ml and f = 17 min -1 , and V t = 800 ml and f = 22 min -1. Each of these combinations was evaluated with Q O2 of 2, 4, and 6 l/min, for the three deviations from the characteristic breathing pattern outlined above.
Baseline experiments The results in terms of oxygen concentration for the 27 baseline experiments that cover a range of breathing patterns and oxygen supply flow rates are given in Additional file 1: Table  S1. The data presented in terms of oxygen concentration, oxygen flux VO2 and volume of oxygen delivered per breath estimated at the interface and measured at the trachea. Data for all 105 cases are also provided in the same table. The dose variability can be interpreted through the plots shown in Figs. 3, 4 , 5 and 6. As shown in Fig. 3a , there is substantial variation (a relative variation by as much as 60%, from 30. 2 to 48. 0% of oxygen, at the same 6 L/min oxygen supply flow rate) in oxygen concentration measured at the trachea for the same oxygen supply flow rate. This result underscores the serious drawback to prescribing supplemental oxygen therapy based solely on the oxygen supply flow rate.
Then, the Minimum fungicidal concentration (MFC) was determined as the lowest antibiotic concentration leading to no significant growth or less than three colonies on Sabouraud agar plates in comparison to the growth control. The experimental data was analyzed using the GraphPad Prism 5. 3 software (GraphPad Inc. , San Diego, CA, USA) to obtain time-kill curves. Additional rows were used to determine the MIC of each antimicrobial agent alone by adding 100 ml of each agent. The fungal inoculum was prepared according to the CLSI standard protocol and 100 μl was added to each well. The plates were incubated under optimal growth conditions for yeasts and filamentous moulds. The results were analysed and MIC 100 were determined visually and by optical density measurements on a microplates reader (Multiskan Spectrum, Thermo Scientific), based on a reduction in absorbance compared to the free drug control wells.
Funding This work was supported by the  French Government  under the  « Investissements d'avenir » (Investments for the Future) program  managed by the  Agence Nationale de la Recherche  ( ANR , fr:  National Agency for Research) , (reference: Méditerranée Infection  10-IAHU-03 ). This work was supported by the  Région Provence-Alpes-Côte-d'Azur and European funding FEDER PRIMI.
Analysis of covariance was used for continuous variables, and the Cochran-Mantel-Haenszel test analysed discrete variables. The efficacy analysis in Period B conducted pairwise comparisons of each adalimumab arm vs. placebo in the Period-B ITT population. According to the study design, patients who lost response during Period B were required to discontinue the study and enter the OLE to receive ADAew, and were counted as nonresponders in the subsequent Period-B visit, even if the patients regained response while continuing ADAew treatment in the OLE. To adjust for this potential study-design artifact, medium-term efficacy of ADAew treatment was also summarized in the all-ADAew population to include data from both the initial PIONEER studies and the OLE study. Safety was analysed for all patients in the Period-A ADAew group who received at least one dose of study drug in Period B.
Acknowledgments The authors would like to acknowledge  Jody Bennett , employed by  AbbVie , for medical writing support in the production of this publication. Fabre,  UCB  and  Regeneron  for participation as an investigator, speaker honoraria from  AbbVie ,  Galderma ,  Leo Pharma  and MSD; and unrestricted research grants from  AbbVie ,  Leo Pharma  and  Novartis. M. M. O. received honoraria from  AbbVie  for advisory board participation and for speaker services, and from  AbbVie ,  Crescendo Biosciences ,  Gilead ,  UCB ,  GSK  and  Innovaderm  for consultant services. M. M. O. was an  AbbVie  employee during this study. S. B. F. has received compensation from  AbbVie ,  AstraZeneca ,  Janssen ,  Novartis ,  Promius ,  Celgene  and  Regeneron  for research; from  AbbVie  for speaker services and from  Galderma  for consultation services.
A. W. A. served as an investigator and/or consultant for  AbbVie, Amgen ,  Janssen ,  Merck ,  Lilly ,  Celgene ,  Novartis ,  Pfizer  and Modernizing Medicine. Y. G. , Z. G. , D. A. W. and H. D. T. were full-time employees of  AbbVie Inc , and owned AbbVie stock and/or stock options. A. B. K. received honoraria as a consultant for  AbbVie ,  Janssen ,  Lilly  and  Novartis , and grants as an investigator from  AbbVie ,  Janssen ,  Novartis  and  UCB , and received fellowship funding from  AbbVie  and  Janssen. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis datasets), in addition to other information (e. g. protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission.