dataesr/scientific-paragraphs-categorization huggingface dataset:
F I G U R E 1 4. 6 | 146 Active mobility according to days of intensive care unit stay Ethical and research approvals The study was approved by the Ethics and Clinical Research Committees of the participating centres. During the first 48 hours of admission, patients who were alert, cooperative, and oriented-or otherwise their next of kin-were asked to give their informed consent. If informed consent was obtained, data collection commenced on day 3 of the ICU stay. 5 | RESULTSWe analysed the data of 642 patients, corresponding to 10 046 patient-days and 80 ICUs, which represent 35% of the 228 ICUs in Spain, according to the database of the Spanish Society for Intensive Care Nurses. FigureS1shows a flow diagram with the patients' movement through the study.
Sampling Purposive sampling, a non-random sampling approach used to select participants as data sources to inform on topics and research questions of interest, was utilised for day one  [13]. Participants were selected to ensure representation of a wide variety of stakeholder groups (government, academic, speciality societies, industry), and had extensive expertise in different domains contributing to the field of medical education (i. e. information technology, epidemiology, medicine, healthcare, business). Day two participants selfselected in the GAME 2019 #FuturistForum by registering, attending, and participating in discussions.
g. "addressing language and culture-related barriers", a sub-code of "technology-based solutions"). The former approach allowed coders a framework within which they could initiate the qualitative coding process, while the latter approach allowed data-derived patterns to reform coding schemes. Transcripts were coded by two independent researchers using NVivo (QSR International Pty Ltd, Version 12, 2018). An evaluation of intercoder reliability was performed to assess coding agreement  [16]. Intercoder reliability results revealed high agreement overall. Coders discussed areas of the coding scheme where coding divergence was present until consensus regarding the final analysis was reached. Further, to ensure trustworthiness of results obtained from qualitative analyses, findings from day one were triangulated with discussion-based data from day two and presented to day one participants during group discussions to ensure patterns reflected exchanges from the two-day event.
Acknowledgments Co-authors want to provide a special thanks to: 1) Thomas Kellner (in memoriam), who provided significant contribution to the conceptualization and execution of the GAME 2019 #FuturistForum, 2) the members of the organizing group of the inaugural GAME Futurist Forum Task Force: co-chair Suzanne Murray, co-chair  Thomas Kellner ,  Dale Kummerle  ( Past President  at the time),  Celine Carrera ,  Celeste Kolanko ,  Dean Beals ,  Matt Frese , and  Alvaro Margolis  (President at the time), 3) the day one Leaders who accepted to engage in the GAME 2019 #FuturistForum, 4) all registered participants of the GAME 2019  #FuturistForum  for their willingness to engage in dialogue on the future of lifelong learning, and 5) members of the research and project management teams at  AXDEV Group Inc.
Patients and method This trial was approved by the French national committee for ethics (CPP, ref: Am7730-2-3439) and registered on ClinicalTrials. gov (NCT03023345). All patients gave their written consent before inclusion. Between September 2017 and 2018, 10 eligible patients were included. The inclusion criteria were:  (1)  age between 45 and 76 years; (2) prostate cancer with a visible index tumor on MRI, confirmed on targeted biopsy, and (3) signed informed consent. Exclusion criteria were: (1) PSA level >15ng/ml, (2) severe low urinary tract symptoms defined by IPSS>18, (3) index tumor largest diameter >20mm, (4) lower distance between index tumor and rectum wall <5mm,  (5)  evidence of extra-capsular extension or seminal vesicle invasion on MRI, (6) evidence of Gleason grade 4 on systematic biopsies, (7) more than 50% of Gleason grade 4 on targeted biopsy, (8) contraindication to general anesthesia, and (9) untreated bacteriuria less than 2 days before surgery.
Funding: The trial was funded by KOELIS (koelis. com) to the clinical research unit of "Assistance Publique -Hopitaux de Paris" (sponsor of the study). Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: N Barry Delongchamps is Consultant for Koelis. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The primary objective was to demonstrate the feasibility and precision of targeted FMA under OBT registration. The primary endpoint was the evidence of complete overlap of the index tumor by ablation zone necrosis on MRI performed 7 days after ablation. Secondary endpoints were: (1) intra and postoperative outcomes, including safety and pain evaluation, (2) urinary and sexual outcomes, assessed with IPSS, IIEF5 and MSHQ-EjD-SF self-questionnaires, respectively (3) oncological outcomes, assessed with PSA at 2 and 6 months, as well as prostate re-biopsy, at 6 months.
With a two-tailed test, a risk alpha of 0. 1 and beta of 0. 1, a total number of 10 patients was considered sufficient. Continuous data were reported as means (sd) or medians [IQR] (for non-normal data), while categorical data were summarized as counts and percentages. To estimate the proportion of patients with complete necrosis of the index tumor 7 days after ablation, a two-sided 95% confidence interval was calculated. A Wilcoxon signed-rank test was used to compare the data from the questionnaires, with a risk alpha of 0. 05. All analyses were conducted using SAS software 9. 4.
Bora contains two short Tpx2-like motifs required for AURKA activation. The microtubule-associated protein Tpx2 is a wellcharacterized allosteric activator of AURKA. The crystal structure of a Tpx2/AURKA complex (PDB: 1OL5) revealed how Tpx2 Fig. 3  phospho-Bora activates dephospho-AURKA and its mimic AURKA T288V. a Two-step in vitro reconstitution of T-loop phosphorylation on T210 of Plk1 KD (pT210) by AURKA WT, AURKA T-loop mutant (T288V), dephosphorylated AURKA (WT dephos ), or catalytically dead AURKA D274N mutant and the activator Bora. In st p 1, Bora is phosphorylated (+) or not (-) by CyclinA2-Cdk2 kinase. In step 2, phosphorylated Bora 1-224 from the reaction mix in step 1 is incubated with AURKA (in the indicated forms) and the kinase domain KD of catalytically dead Plk1 K82R. b Western blot analysis of kinase reactions carried out with Bora 1-224 phosphorylated (+) or not (-) by CyclinA2-Cdk2 (step 1) in the presence of Plk1 K82R KD and the indicated forms of AURKA, namely WT phosphorylated, WT dephosphorylated, T288V mutant, or D274N mutant (step 2).
Blots were probed with antibodies to Bora, AURKA, and phosphoT210 Plk1 or pan Plk1 as indicated (from top to bottom). In the blot performed with the anti-pT210 Plk1 antibody, the asterisk denotes the cross reactivity with the pT288 residue of AURKA WT. c, d Activation of AURKA WT (c) or AURKA T288V (d) kinase activity by Bora  and pBora  as assessed using the ADP-Glo assay and Kemptide substrate. Displayed data points and EC 50 values represent the average luminescence for each reaction condition with standard deviations of the mean as error bars (n = 3 independent experiment samples). RLU: relative light unit. ND: n t determined. React on results carried out in the absence of Kemptide are shown in Supplementary Fig. 3c, d. e, f SPR binding analysis of immobilized Bora  (e) and pBora  (f) to AURKA T288V.
This would involve coordination by Arg255, Arg180, and Arg286 (Fig. 7a  and Supplementary Fig. 1 ). To our knowledge, no precedent for a kinase regulator acting in this manner has been described. An alternate possibility is that the phosphoSer112 motif binds to a different site on AURKA from the phosphorylated T-loop. For example, a Tpx2-AURKA co-structure (PDB: 1OL5) reveals an adjacent and partially overlapping binding site involving His176, Arg180, and Arg286 that coordinates a free sulfate ion (Fig. 7a ). A precedent for this site in coordinating phosphate was established for AURKC, which is regulated by binding to the centromere and mitotic regulator INCENP  50. One of two phospho-sites in INCENP (within a TSS motif) binds to the corresponding sulfate binding site conserved with AURKA (see Supplementary Fig.
7d ). Taken together, these data provide compelling evidence that His176, Arg180, Arg286, and Arg255 participate in coordinating the phospho-S112 moiety in Bora that is required for the robust activation of AURKA T288V. The results are further consistent with a model in which a phospho-S112 moiety in Bora functionally and perhaps structurally substitutes for the phospho-T288 moiety on the T-loop that is normally required to activate AURKA (Fig. 7e ). Bora determinants are critical for mitotic entry in Xenopus egg extracts. Having determined that the Tpx2-like motifs (M1 and M2) and the phosphorylated serine Ser112 (M3) are essential in the context of the minimal Bora  fragment for function in vitro, we next investigated the relevance of these determinants for Bora function in vivo. We fir t investigated Bora function at mitotic entry in Xenopus egg extracts using a variation of the experimental setup described earlier, whereby interphase egg extracts are forced to enter into mitosis using the Gwl kinase  27, 45.
Collectively, these results indicate that the Tpx2-like motifs (M1, M2) and S112 phosphorylation (M3) are essential determinants for Bora function in Plk1 activation and mitotic entry during the human cell cycle. These results are also fully consistent with our in vitro data and results obtained in Xenopus egg extracts. Fig. 6  Bora and Tpx2 1-43 compete for AURKA binding. a Schematics of a competitive displacement binding assay using fluorescein-labeled Tpx2  (FITC-Tpx2  ) as a probe. Comp x formation between FITC-labeled Tpx2 1-43 polypeptide and AURKA followed by the disassembly of the FITC-Tpx2 1-43 /AURKA complex by increasing amount of competitor (cold Tpx2  , Bora, or pBora) was monitored by fluorescence polarization. b Binding of fluorescein-labeled Tpx2 1-43 polypeptide to AURKA WT assessed by monitoring the fluorescence polarization signal in the presence of increasing concentrations of AURKA WT.
K d value represents mean value with standard deviations of the mean as error bars (n = 3 independent experiment samples). c Competitive binding assay where fluorescein-labeled Tpx2 1-43 polypeptide in complex with AURKA WT is displaced by increasing amount of competitor (cold Tpx2 1-43 , Bora  , or pBora  ) and monitored by fluorescence polarization signal. Displayed data points and the half maximal inhibitory concentration (IC 50 ) value represent the average fluorescence polarization for each reaction conditions with standard deviations of the mean as error bars (n = 3 independent experiment samples). ND:  ot determined. d Binding of fluorescein-labeled Tpx2 1-43 polypeptide to AURKA T288V assessed by monitoring the fluorescence polarization signal in the presence of increasing concentrations of AURKA T288V.
K d value represents mean value with standard deviations of the mean as error bars (n = 3 independent experiment samples). e, f Competitive binding assay where fluorescein-labeled Tpx2 1-43 polypeptide in complex with AURKA T288V is displaced by increasing amount of cold Tpx2, Bora  , or pBora  competitor (e), or by increasing amounts of cold pBora  , pBora  , or the indicated pBora  mutants in the M1 and M2 motifs. Data presented as in c. g Activation of AURKA WT ATPase activity by Bora  , pBora  , and Tpx2 1-43 as assessed using the ADP-Glo assay with Kemptide substrate. Displayed data points and EC 50 values represent the average luminescence for each reaction condition with standard deviations of the mean as error bars (n = 3 independent experiment samples). RLU: relative light unit. h Activation of AURKA T288V ATPase activity by Bora  , pBora  , and Tpx2 1-43 as assessed using the ADP-Glo assay with Kemptide substrate.
Data presented as in g. i Activity of the AURKA T288V /pBora  complex in the presence of increasing concentration of competitor Tpx2  or Bora  assessed using the ADP-Glo assay in the presence of Kemptide substrate. Displayed data points and the half maximal inhibitory concentration (IC 50 ) value represent the average fluorescence luminescence for each reaction conditions with standard deviations of the mean as error bars (n = 3 independent experiment samples). and sustained by CyclinB1-Cdk1 (refs. 25, 52  ). Based on similarity to Tpx2, we speculate that Bora motif M1 binds in an extended manner parallel to the top surface of helix αC whereas motif M2 adopts a helical conformation and binds parallel to the bottom surface of helix αC (Fig. 7a ). As Bora motif M3 is located immediately C-terminal to motif M2, this binding model is attractive because it orients the Ser112 phospho-moiety in motif M3 in close proximity to two possible phosphate coordination sites in AURKA.
All protein-protein interactions were tested at 25 °C, flow rate 10 µL/min; injection time 120 s; dissociation time 600 s. Regeneration of the chip surface was performed after each cycle using 30 s injection of 10 mM glycine pH 3 at increased flow rate of 30 μL/min. After regeneration, the sensograms returned to baseline. Raw sensogram data were analyzed and fit using Biacore S200 analysis software (Cytiva). ADP-Glo TM assay. The ATPase activity of recombinant AURKA was evaluated using the ADP-Glo assay Kinase kit (Promega). Bora  or pBora  was titrated into 10 nM of AURKA WT or AURKA T288V in a buffer containing 40 mM Tris pH 7. 5, 150 mM NaCl, 10 mM MgCl 2 , 1 mM DTT, 0. 1 mg/mL BSA, and 0. 01% Brij 35. The final reaction volume was 20 µL. When  00 μM Kemptide (LRRASLG, Cedarlane) was present in the reaction mix, the AURKA concentration was reduced to 2 nM.
05 software with excitation and emission at 485/528 nm, respectively. Binding graphs and the derived binding constants were generated using GraphPad Prism v8. 1. 2 an  v8. 3 (GraphPad). Intact protein mass spectrometry. The liquid chromatography mass spectrometry (LC-MS) system consisted of a 1260 series HPLC connected to 6538 UHD series electrospray ionization quadrupole time-of-flight mass spectrometer (Agilent Technologies, Santa Clara, CA). Approximately 2. 5 µL aliquots of protein samples (~0. 1 µM) dissolved in a 0. 1% formic acid buffer were separated on a 2 mm × 50 mm Sprite C4 column (Higgins Analytical Inc. , Mountain View, CA). The mobile phase was composed of A: 0. 1% aqueous formic acid and B: acetonitrile (Fisher Scientific Company, Ottawa, ON). The flow rate was 0. 25 mL/min and proteins were eluted rapidly using a linear gradient of 5-80% B over 5 min.
Mass spectrometry data were collected up to 2500 m/z and raw spectra were deconvoluted using the maximum entropy algorithm of the Agilent MassHunter software version B. 06. 01. The peak numbering corresponds to the molecular weight of the protein plus the indicated number of phosphate groups (+79. 99 Da/phosphate group). NMR spectroscopy. NMR-HSQC spectroscopy spectra (8 scans, 20 min acquisition time) were recorded at 15 °C on a 600-MHz Bruker AVANCE III spectrometers equipped with a 1. 7-mm TCI CryoProbe. All NMR samples contained 180 µM of  15  N-Bora 1-224 or 15 N-phospho Bora 1-224 in 25 mM Tris pH 7. 5, 150 mM NaCl, 1 mM TCEP and 10% D 2 O. Data processing was conducted using NMRviewJ and NMRpipe 69 , and NMR spectra were analyzed using Analysis  70. Preparation of Xenopus extracts. CSF extracts were obtained from metaphase IIarrested oocytes.
Imaging was performed using an inverted microscope (Nikon Eclipse TI-E) controlled by Metamorph software and equipped with perfect focus system, fast emission filter wheel (lambda 10-3, Sutter), electron multiplying charge coupled device camera (iXon 3 888 Ultra Andor), Plan Apochromat 20×/NA 0. 75 lens, and light-emitting diode (LED)-based illumination system (spectra X-light engine, Lumencor). Filters used for IFP2 were ET620/60x, T660lpxr beamsplitter, and ET700/75m from Chroma. Quantifications were performed using ImageJ software.
Acknowledgements We thank  P. Moussounda  and  R. Servouze  ( Institut Jacques Monod ) for help with media preparation,  M. Cobb ,  E. Nigg ,  A. Santamaria ,  M. Kanemaki ,  F. Zhang ,  T. Mittag  for sharing plasmids and  D. Durocher  for the recombinant Histone H3 protein. We acknowledge the  ImagoSeine core facility  of the  Institut Jacques Monod , member of IbiSA and the  France-BioImaging  ( ANR-10-INBS-04 ) infrastructure. NMR spectrometers were funded by the  Canada Foundation for Innovation  and the  NMR Core Facility  was supported by the  Princess Margaret Cancer Foundation. We acknowledge  Matthew Forbes  from the  AIMS (Advanced Instrumentation for Molecular Structure) Mass Spectrometry Laboratory of University of Toronto  ( Department of Chemistry ) for his help regarding intact mass-spectrometry.
Research was supported by the  Fondation ARC  ( PJA 20181207931  to L. T. ), the  Agence Nationale de la Recherche  ( AMBRE  Project  ANR-17-CE13-0011  to P. L. , L. T. , and G. O. ), the  Labex EpigenMed  ( ANR-10-LABX-12-01  to C. A. , L. T. ),  Ligue Nationale Contre le Cancer  (programme équipe labelisée to P. L. ), the  Canadian Cancer Society  ( CCSRI-Impact 704116  to S. F. ), the  Canadian Institutes of Health Research  ( FDN 143277  to S. F. ; FRN 414829 to Mai. P. ), and the  Terry Fox Research Institute  (to S. F. ). T. N. was supported by postdoctoral fellowships from the  "Fondation pour la Recherche Médicale " (SPE20150331777) and from the  CIHR  ( MFE 152464 ). T. Y. was supported by a post-doctoral fellowship from the  LabEx "Who Am I?"  (# ANR-11-LABX-0071 ) and the  Université de Paris  (IdEx # ANR-18-IDEX-0001 ) funded by the  French Government  through its " Investments for the Future" program.
J. N. was supported by the  Fondation ARC pour la Recherche sur le Cancer  and is supported by funding " Dynamic Research"  from  Agence Nationale de la Recherche  ( ANR-18-IDEX-0001 ),  Université de Paris excellency initiative (IdEx). VA. G. is supported by  CONACYT  (grant  CVU 364106 ). R. S. and D. M. are supported by the  National Institute for Child Health and Human Development Intramural  project  Z01 HD008954.
Identification of the CsKAT2 and ClKAT2 Shaker channel genes The Shaker Channel genes CsKAT2 (GenBank accession number MF447463) and ClKAT2 (GenBank accession number MF447464) were obtained by PCR. The open reading frame (ORF) of CsKAT2 was 2100 bp long encoding a 700 amino acid polypeptide, and ClKAT2 contained 2061 bp encoding a 687 amino acid polypeptide. Results of BLAST revealed a high degree of homology between amino acid sequences of CsKAT2, ClKAT2 and MIRK. CsKAT2 and ClKAT2 shared 91% and 90% amino acid identity with MIRK, respectively. These three channels shared, respectively, 62%, 61% and 62% amino acid identity with KAT2 from Arabidopsis. They all displayed high sequence conservation in the pore domain with the putative K + transport motif (TTLTTTGYGD), which is common to the other Shaker channel genes  (Fig S1).
Two-electrode voltage clamp experiments Two to four days after injection, whole-cell currents were measured using the two electrode voltage-clamp technique using a GeneClamp 500B amplifier (Axon Instruments, Foster City, CA, USA). Voltage-pulse protocols, data acquisition and data analyses were performed using pClamp 9 (Axon Instruments, Foster City, CA, USA) and Sigmaplot 8 software (Jandel Scientific, Erkrath, Germany). All electrodes were filled with 3M KCl. Both actual imposed membrane potential and current were recorded. A correction was made for the voltage drop occurring through the series resistance of the bath and the reference electrode by using two external voltage-measuring electrodes connected to a bath probe (VG-2A-X100 Virtual ground bath clamp; Axon Instruments). Except in the pH sensitivity experiments, all the other measurements were performed in the background solution containing 1.
Acknowledgement We are grateful to  Dr. Gareth Steed  from the  University of Cambridge  for his critical reading. We also thank  Dr. Ruth Le Fevre  for language polishing. Downloaded from https://academic. oup. com/pcp/advance-article/doi/10. 1093/pcp/pcab170/6447658 by  INRAE Institut National de Recherche pour l'Agriculture , l'Alimentation et l'Environnement user on 03 December 2021.
The following measurements were assessed on the surface ECG of the first beat of VT or the PVCs: (1) QRS duration; (2) R-wave amplitude and the duration from the onset of QRS to the peak of QRS deflection in leads II, III, aVF; (3) R-wave ratio of leads III/II 10 ; (4) Qwave amplitude in leads aVL and aVR; (5) R-and S-wave amplitudes in leads V 1 to V 3 ; (6) R-wave duration in leads V 1 to V 3 ; (7) aVL/aVR Q wave ratio; (8) R/S ratio in leads V 1 to V 3 ; (9) V 2 S/V 3 R index 7 ; (10) V 2 transition ratio; (11) peak deflection index in the inferior leads 11 ; (12) precordial transition in LBBB morphology. During the sinus beats, R-and S-wave amplitudes in lead V 2 were also measured on the surface ECG. The ECG data were measured with electronic calipers by 2 experienced investigators blinded to the site of the origin.
using automated pace-map algorithms integrated in a 3-D mapping system (PaSO software; Biosense Webster). The sites mapped with the earliest ventricular activation or exhibiting a perfect (12/12) or near-perfect (10-11/12) pace match were determined as the target site. When the earliest ventricular activation site was recorded at the LVOT, selective coronary angiography was performed to define the anatomical relationship between the aortic cusps, the coronary arteries, and the ablation catheter. RF ablation was performed in a power-control mode starting at 15 W in the GCV-anterior intraventricular vein, 30 W in the RVOT, and 30-40 W in the LVOT with an irrigation flow rate of 17-30 mL/min (normal saline 0. 9%) and a temperature limit of 43 C. Ablation was performed at least 5 mm from the ostium of any coronary artery.
Statistical analysis The data were analyzed using SPSS 26. 0 (IBM, Armonk, NY). Continuous data are expressed as the mean 6 standard deviation or median, interquartile range (IQR) as appropriate. Comparisons between groups were performed using Student t test or the Mann-Whitney U test for normally and nonnormally distributed data, respectively. A receiver operating characteristic analysis was used to compare the accuracy among the different ECG criteria and to calculate the sensitivity, specificity, and area under the curve (AUC). A value of P ,. 05 was considered statistically significant.
| Data collection Vegetation surveys started in May 2008 and were repeated year by year in the same period, which is expected to correspond to the optimum development of pond vegetation through 2013. The surveys were by the same observer each year. Plant cover was assessed in each plot in one 60 cm × 60 cm quadrat subdivided in 36 sub-quadrats. In each sub-quadrat cover of each species was visually assessed using the following scores: 0 (cover = 0%); 1 (cover = 1%-25%); 2 (cover = 26%-50%); 3 (cover = 51%-75%); 4 (cover = 76%-100%). The scores for each species inside each quadrat were summed and reported relative to the maximum possible cover value (i. e. Σscores ispecies × 100/36;  Dethier et al. , 1993). We assigned two attributes to each species: a biological life-form, according to  Raunkier (1934)  and  Pignatti et al.