dataesr/scientific-paragraphs-categorization huggingface dataset:
(G) For all crawling T cells eventually starting to transmigrate, the time span between halt of movement and start of diapedesis was calculated. (H) For all T cells that finished diapedesis, the duration of diapedesis was calculated. (I) T cells, which eventually started to transmigrate, were classified according to their prior behavior: crawling or stationary. Data are derived from 9 videos per pMBMEC genotype performed in three independent experiments. Error bar, ± SD; FOV, field of view; ns, not significant. Reported statistics result from unpaired, two-tailed Student's t-tests. Test statistics for (C): p = 0. 0488, t(16) = 2. 132 (d = 1. 066); *p < 0. 05; ns, not significant. showed comparable levels of ICAM-1 protein in WT and PECAM-1 -/-pMBMECs under both conditions (Figure  7A ). Quantification of Western blot signals showed that ICAM-1 expression did not significantly differ between IL-1β-treated WT and PECAM-1 -/-pMBMECs, although ICAM-1 signals varied to a greater extent in PECAM-1-deficient pMBMEC samples (Figure  7B ).
(D-F) Each T cell crawling on the activated endothelial monolayer was tracked and the crawling speed (D), accumulated crawling distance (E), and Euclidian crawling distance (F) were calculated. (G) For all crawling T cells eventually starting to transmigrate, the time span between halt of movement and start of diapedesis was calculated. (H) For all T cells that finished diapedesis, the duration of diapedesis was calculated. (I) T cells, which eventually started to transmigrate, were classified according to their prior behavior: crawling or stationary. Data are derived from 9 videos per pMBMEC genotype performed in three independent experiments. Error bar, ± SD; FOV, field of view; ns, not significant. Reported statistics result from unpaired, two-tailed Student's t-tests. Test statistics for (C): p = 0.
ACKNOWLEDGMENTS We gratefully acknowledge the expert technical and experimental support from  Claudia Blatti ,  Mariana Dias ,  David Jarrossay ,  Elisa Kaba ,  Ulrike Köck ,  Angela Kury ,  Daniela Latorre ,  Marianne Leißer ,  Mark Liebi ,  Albert Witt , and  Tobias Zrzavy  (list in alphabetical order). We furthermore express our thanks to our animal caretakers for state-of-the art experimental animal husbandry.
FUNDING This study was supported by the  Swiss National Science Foundation  ( SNSF  grants  N • 133092  and  170131 ) and the  EU   FP7  funded collaborative project  JUSTBRAIN  ( HEALTH-F2-2009-241861 ) and the  Bangerter-Rhyner Foundation  to BE, the  SNSF  funded  Sinergia  project  UnmetMS  ( CRSII3_154483 ) to BE and FS, the  Austrian Science Fund  (grant N •  W1205-B09 [II]) to HL, a  Du Pré Grant  of the  MS International Federation  to IW and by an  ECTRIMS   Postdoctoral Research Exchange Fellowship  and the  Uehara Memorial Foundation  to HN.
FUNDING AS thanks the  National Science Centre  (grant SONATA  BIS 2018/30/E/ST5/00032 ) for financial support. SU thanks the  ANR  ( ANR-17-CE07-0042-01 ) for funding. MK and PC thank grant INNCHEM no. POWR. 03. 02. 00-00-I023/17  co-financed by the  European Union  for financial support.
After washing the cultures and performing a background reading, primary human airway epithelial cells (hAECs) ASL are loaded with dextran coupled pH-sensitive and pHinsensitive dye mixture overnight at 37 °C, 5% CO 2. The following day, the plate is transferred to a temperature and CO 2 -controlled plate reader and fluorescence from both dyes is recorded over time. After the experiment, an in situ calibration is performed and data analyzed and presented as ASL pH over time.
Acknowledgments This work was supported by two  CF Trust Strategic Research Centre grants  ( SRC003  and  SRC013 ) and a  Medical Research Council (MRC)   Confidence in Concept grant  ( MC_PC_15030 ). JG was supported by a grant from the  Medical Research Foundation  ( MRF-091-0001-RG-GARNE ). MB was supported by a  Medical Research Council   Clinician Scientist Fellowship  ( MR/M008797/1 ). IH was supported by a  Wellcome Trust   Clinical Training Fellowship  ( 203520/Z/16/Z ). The research was supported by the  National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the  NHS , the  NIHR  or the Department of Health. Primary cells from  Dr.
Speckle Measurements Images of the scattering spot for each apple slice are taken under different exposure durations Texp, ranging from 1. 5 to 98 ms. To make sure that all images over the whole range of exposure durations have the same mean intensity, the laser's intensity is automatically adjusted repeatedly, with a maximal power of 20 mW at shorter times. For each exposure duration, 40 images are averaged out: all images, from all exposure durations, are added up to form a global image of the diffuse light averaged intensity. On this image, an internally developed algorithm that detects circular patterns is used to identify the center of the scattering spot and eliminate large-scale inhomogeneous zones. This algorithm is based on the cylindrical symmetry expected from the averaged intensity: for each distance  (in pixels) from the scattering spot center, we extrapolate   = 4 intensity values from the recorded data along the circle of radius.
Speckle Measurements Images of the scattering spot for each apple slice are taken under different exposure durations T exp , ranging from 1. 5 to 98 ms. To make sure that all images over the whole range of exposure durations have the same mean intensity, the laser's intensity is automatically adjusted repeatedly, with a maximal power of 20 mW at shorter times. For each exposure duration, 40 images are averaged out: all images, from all exposure durations, are added up to form a global image of the diffuse light averaged intensity. On this image, an internally developed algorithm that detects circular patterns is used to identify the center of the scattering spot and eliminate large-scale inhomogeneous zones. This algorithm is based on the cylindrical symmetry expected from the averaged intensity: for each distance r (in pixels) from the scattering spot center, we extrapolate N(r) = 4πr intensity values from the recorded data along the circle of radius r.
Strains and deformations were measured using Vishay CEA-06-250UR-350 strain gauges. Data from the Strain gauges were logged, stored and evaluated using the BMCM acquisition system  [72]  and the NextView 4. 2 data acquisition software  [73]  enabling a real-time data presentation. Additionally, full field deformation measurements of each panel using   a digital image correlation system (DIC) was present to record the out-of-plane displacements. A Dantec Q-400 optical contactless full field measurement system was used for the strain and deformation measurements. The Dantec Q-400 was controlled using the ISTRA 4D software package  [74]. An overview of the test frame with the test panel and Dantec Q-400 camera is shown in Figure  15.
A better understanding of the proportion and characteristics of patients who can derive long-term benefit and maintain tolerability is needed for optimal treatment strategies, which remains an unmet clinical need with the current therapies in this population. In the current analysis of the phase 3 METRIC study (NCT01245062), we report a minimum 5-year follow-up data of trametinib (MEK inhibitor) monotherapy. At the time this trial was originally designed and implemented, the superiority of targeted combination (BRAF and MEK inhibitors) therapy over monotherapy had not been established. In a previously reported primary analysis, the median PFS was 4. 8 months in the trametinib arm and 1. 5 months in the chemotherapy arm (hazard ratio [HR], 0. 45; 95% confidence interval [CI], 0. 33-0. 63; P < 0.
Study design and treatment METRIC (TMT212A2301; NCT01245062) was a randomized, open-label, multicenter, phase 3 study to evaluate the efficacy and safety of trametinib monotherapy versus chemotherapy (dacarbazine or paclitaxel). The study design, treatment regimen, patient population, and end points have been reported previously  [12]. Patients with unresectable or metastatic cutaneous melanoma with a BRAF V600E/K mutation were randomized in a 2:1 ratio to receive either oral trametinib (2 mg once daily) or intravenous chemotherapy consisting of either dacarbazine (1000 mg/m 2 of bodysurface area) or paclitaxel (175 mg/m 2 ), every 3 weeks, at the discretion of the investigator. Patients were stratified by baseline lactate dehydrogenase (LDH) levels (normal vs elevated) and prior chemotherapy for advanced disease (yes or no).
Acknowledgments The authors acknowledge the patients, their families, and their caregivers, as well as all the investigators. The METRIC study group is grateful to all the physicians who contributed to the present study, the worldwide network of research nurses, trial coordinators, and operations staff for their contributions. We appreciate the support of the colleagues of the  METRIC Study Team  who contributed to the presented data. In addition, we thank  Rajasree Solipuram ,  Rohitbhai Kachhadiya , and  Sharol Janice Rodrigues  of  Novartis Healthcare Pvt. Ltd. , for providing medical editorial assistance with this manuscript.
Funding Information Open access funding provided by  MTA Wigner Research Centre for Physics (MTA Wigner FK, MTA EK). The authors received funding from the  National Research, Development and Innovation Office of Hungary  (grants  VEKOP-2. 3. 2-16-2017-00015 , 2018-1. 2. 1-NKP-2018-00012  and  128077 ), and the  PETACom  project no. 829153  financed by the  FET Open H2020 program.
In the adult human liver, rare EPCAM + cells have been termed hepatic stem cells  34. These cells can form dense round colonies when cultured and have been reported to be bi-potent progenitors of hepatoblasts, which differentiate into cholangiocytes or hepatocytes both in vitro and in vivo  34, 35. In search for the genuine liver stem cell, we sorted and sequenced single EPCAM + cells from adult human livers. The EPCAM + cells that we sequenced were negative for proliferation markers MKI67 and PCNA and the hepatoblast marker AFP (Extended Data Fig. 7a ). This suggests that the heterogeneity in the EPCAM + compartment is not arising as a result of proliferation but that the observed sub-types reside in the normal human liver. Using our approach, we discovered novel liver stem cell surface markers whose expression correlates with that of EPCAM or TROP1; these include TACSTD2 (TROP2), CD24, FGFR2, AQP1, DEFB2, TM4SF4 and CLDN4 (Fig.
The remainder of the left read contains a polyT stretch. The left read was not used for quantification. For each cell barcode, the number of UMIs per transcript was counted and aggregated across all transcripts derived from the same gene locus. Based on binomial statistics, the number of observed UMIs was converted into transcript counts  56. Single-Cell RNA Sequencing Data Analysis. 5416 cells passed quality control thresholds for the normal human liver cell atlas. For cells from the organoids, 625 cells passed the quality control thresholds. For cells from HCC, 911 cells passed the quality control thresholds. For cells from the humanized mouse, 315 cells passed the quality control threshold. All the datasets were analyzed using RaceID3 10. Rescaling to 1,200 transcripts per cell was applied for data normalization.
Prior to normalization, cells expressing >2% of Kcnq1ot1 transcripts, a previously identified marker of low quality cells were removed from the analysis. Moreover, transcripts correlating to Kcnq1ot1 with a Pearson's correlation coefficient >0. 65 were also removed. RaceID3 was run with the following parameters: mintotal=1200, minexpr=5, outminc=5, FSelect=TRUE, probthr=10 -3. The tdistributed stochastic neighbor embedding (t-SNE) algorithm was used for dimensional reduction and cell cluster visualization. Diffusion Pseudo-Time Analysis and Self-Organizing Maps. Diffusion pseudotime (dpt) analysis  28  was implemented and diffusion maps generated using the destiny R package. The number of nearest neighbors, k, was set to 100. SOMs were generated using the FateID package based the ordering computed by dpt as input.
Pathway Enrichment Analysis and Gene Set Enrichment Analysis. Symbol gene IDs were first converted to Entrez gene IDs using the clusterProfiler  57  package. Pathway enrichment analysis and GSEA  58, 59  were implemented using the ReactomePA 60 package. Pathway enrichment analysis was done on genes taken from the different modules in the SOMs. GSEA was done using the differentially expressed genes inferred by the diffexpnb function from the FateID package without filtering on lowly expressed genes. Immunofluorescence. Human liver tissue was fixed in 3. 7% formaldehyde. The tissue was then embedded in OCT and kept at -80 o C. The tissue was cryosectioned into 5 micron sections. The tissue was washed twice for 5 min in 0. 025% Triton 1x TBS (Tris-Buffered-Saline). The tissue was then blocked in 10% FBS with 1% BSA in 1x TBS for 2 hours at room temperature.
Acknowledgments This study was supported by the  Max Planck Society , the  German Research Foundation (DFG)  ( SPP1937 GR4980/1-1 ,  GR4980/3-1 , and  GRK2344   MeInBio ), by the  DFG under Germany's Excellence Strategy  ( CIBSS -EXC-2189 -Project ID 390939984 ), and by the  Behrens-Weise-Foundation  (all to D. G. ). This work was supported by  ARC ,  Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC  and  TheraHCC2. 0IHUARC IHU201301187  and  IHUARC2019  to T. F. B. ), the  European Union  ( ERC-AdG-2014-671231-HEPCIR  to T. F. B. ,  EU   H2020-667273-HEPCAR  to T. F. B, ERC-PoC-2016-PRELICAN to T. F. B),  ANRS  and the  Foundation of the University of Strasbourg. This work was done under the framework of the LABEX  ANR-10-LABX-0028_HEPSYS  and  Inserm Plan Cancer  and benefits from funding from the state managed by the  French National Research Agency  as part of the Investments for the future.
STATISTICAL ANALYSIS Bone and soft tissue window NCCT results were compared using paired T-test, Wilcoxon Signed Rank. Bone and soft tissue window NCCT residual fragments were compared using McNemar-Bowker test of symmetry. Sample size was calculated based on the percentage of renal units with residual fragments more than 2mm by NCCT of 38%  (20). Therefore, the sample size for a bicaudal test with significance level of 5% and test power of 95% is 115 renal units. SAS 9. 0 program® (SAS Institute Inc. , Cary, NC, USA) was used with a significance level of 5%. me and density differed between the two methods (p <0. 0001). Although residual fragments diameter was not significantly different when evaluated by NCCT using bone or soft tissue window (p=0. 1116) (Table -2), 5. 2% of the renal units (6/115) were reclassified from residual fragments >2mm to 0-2mm.
A single senior radiologist evaluated all NCCT studies, in a different time, blinded for the results of the bone window NCCT stone measurements. This might have reduced the possible measurement bias. Magnified bone window NCCT should be preferred for urinary stone evaluation due to better image quality for dense objects as it minimizes noise artifacts close to the stone limits  (12, 25). In vitro study already demonstrated that soft tissue window overestimates stone size and bone window provides best accuracy  (26). Clinically, it was shown that bone window allows a visual distinction between a stent and a stone  (28, 29). On the other hand, urologists are more familiar with soft tissue window when looking at NCCT and most data related to stone features and NCCT were produced using soft tissue window.
Methods Optical polarized light and hot-stage microscopy (HSM): Microscopic observations were performed with an Olympus BH-2 polarized light microscope (Olympus Optical GmbH, Vienna, Austria) equipped with a polarizer and a rotatable analyzer. For thermo-microscopic investigations, the microscope was equipped with a Kofler hot stage (Reichert Thermovar, Vienna, Austria). Photomicrographs were taken using an Olympus DP50 microscope stage digital camera with a resolution of 5. 8 million pixels, operated through the AnalySIS 3. 2 software (Soft Imaging System GmbH, Hamburg, Germany). Differential scanning calorimetry: DSC measurements were conducted using a Diamond HyperDSC (Perkin Elmer, Norwalk, Ct, USA) equipped with a Controlled Cooling Accessory CCA 7 and operated with Pyris 7. 0 software.
999%, m. p. 156. 6 °C, heat of fusion 28. 45 J/g). Thermogravimetric analysis (TGA): TGA curves were recorded using a TGA7 thermogravimetric system (Perkin-Elmer, Norwalk, Ct. , USA) operated with Pyris 2. 0 software. Samples of approximately 2-6 mg were accurately weighed (±0. 0005 mg) into 50 μL platinum pans and subjected to non-isothermal TGA at a heating rate of 10 K/min in a temperature range from 25 to 220 °C. Nitrogen was used as a purge gas (balance purge: 50 mL/min, sample purge: 25 mL/min). Moisture sorption/desorption experiments: Dynamic moisture sorption and desorption were determined gravimetrically at 25 °C using an automatic multi-sample moisture sorption analyzer (SPS11, Projekt-Meßtechnik, Ulm, Germany). Approximately 1. 0 g of accurately weighed crystals (balance resolution: 10 μg) were placed in an aluminium sample dish (diameter: 5 cm), transferred into the sample compartment of the moisture sorption analyzer, and equilibrated at 0% RH.
The RH was cycled in 10% steps up to 90% RH and back down to 0% RH. The mass change of the material was recorded every 8 min with the equilibrium condition set to <0. 001% within 35 minutes and the maximum residence time to 24 hours for each RH level. The mass change at each RH step was used to draw the moisture sorption isotherms. Powder and single-crystal X-ray diffraction: Powder X-ray diffraction data for phase characterization were collected on a Stoe STADI MP diffractometer in bisecting flat-plate transmission geometry. The diffractometer is equipped with an asymmetric primary beam Ge(111) monochromator (yielding strictly monochromatic Cu-Kα1 radiation) and a linear position sensitive detector with 4° detector range. In transmission geometry the axial beam width was set to 2 mm. The samples were prepared in quartz glass capillaries of 0.
7 mm in diameter and placed in a STOE 0. 65. LT furnace. Forms A and B as well as the dihydrate were measured at room temperature. Forms H, I and J were measured at 70, 30 and -30 °C, respectively. The temperature-controlled measurement of the remaining crystal forms was started at 25 °C and the temperature raised in 5 °C steps up to 100 °C, then in 10 °C steps to 180 °C. Subsequently, the temperature was decreased in 20 °C steps to 100 °C and further to 25 °C in 5 °C steps. The data collection was started 2 min after the respective temperature was reached, and each temperature step was measured for 1 h. The absolute accuracy of the temperatures is ±1 °C, temperature stability is ±0. 3 °C and total temperature gradient over the length of the sample is <1 °C. The crystal structure of polymorph B was determined from powder diffraction data measured carefully in the range from 2 to 80˚ 2θ.
Neutron single-crystal diffraction: A single crystal of the dihydrate of size 3 × 1. 5 × 0. 75 mm 3 was mounted on a vanadium pin with vacuum grease and placed in a helium-flow cryostat on the Very-Intense Vertical-Axis Laue Diffractometer (VIVALDI)  35, 36  at the Institut Laue-Langevin, Grenoble, France. Data were collected from the stationary crystal at 290, 260 and 20 K using a white neutron beam with wavelengths between 0. 8 and 5 Å. The crystal was rotated 20° about an axis perpendicular to the incident neutron beam between Laue patterns, which were recorded in exposures of 90 min. The patterns were indexed using the program LAUEGEN,  37, 38  and the reflections were integrated using the local program INTEGRATE+  39  and normalized to a common incident wavelength using the program REARRANGE.
Above 50% RH, the material takes up two moles of water in a stoichiometric, single-step behavior forming the known room-temperature dihydrate. The X-ray crystal structures were obtained for both the room-temperature and the lowtemperature form of the dihydrate. In addition, neutron single-crystal diffraction was performed on VIVALDI  35  at the Institut Laue-Langevin, France, to accurately locate and anisotropically refine the hydrogen atom positions. Neutron data were collected at 290 K (room-temperature hydrate), 260 K (low-temperature hydrate) and 20 K for the most accurate positions and lowest thermal motion. The following structural discussion is based on the structures refined against neutron data. The room-temperature form crystallizes in the triclinic space group P-1 and contains half a molecular unit in the asymmetric unit with the hexamidine on the inversion center.
S5 ). It is surprising that the pattern of form H shows close resemblance to form B, but contamination with form B can be excluded as the pattern of form H was recorded at a temperature that is outside its stability range. With the thermodynamic data extracted from the DSC thermograms (table  S2 ), it was possible to construct a semi-schematic energy-temperature diagram for HDI based on the heat of fusion and the heat of transition rules established by Burger and Ramberger (Fig. 9 ). 48, 49   his diagram depicts schematically the Gibb's free energy G and the enthalpy H over temperature of each polymorph along with those of the melt. In the case of two polymorphs having G-isobars intercrossing at a temperature below the melting point, this pair is enantiotropically related with a transition point at the crossing.
Funding DI was supported by a fellowship from the  Uehara memorial foundation research (Japan). DO was supported by a fellowship from the  Fondation pour la Recherche Médicale  ( FDT20150532056 ). Funding was obtained from the  Association Nationale pour la Recherche  ( ANR-PoLyBex-12-BSV3-0014-001  to A-ML-D and  ANR-Mitotube-12-BSV5-0004-01  to MT) and the  European Research Council  ( ERC-Strapacemi-GA 243103  to A-ML-D and  ERC-SpiCy   310472  to MT).
Background: The feasibility of day case surgery (DCS) appendectomy for uncomplicated acute appendicitis (UCAA) was evaluated by the prospective AppendAmbu study (NCT01839435). The aim of this study was to evaluate the real-life feasibility of DCS for UCAA. Study design: This single-center, retrospective, non-interventional study was conducted after the AppendAmbu study and only included UCAA. The primary endpoint was the DCS success rate (LOS less than 12 hours) in the intention-to-treat (ITT) population (all patients with UCAA) and in the per protocol (PP) population (population with UCAA and no preoperative and intraoperative exclusion criteria). The secondary endpoints were to determine the DCS quality criteria to evaluate and compare the morbidity and mortality of DCS and conventional hospitalization for UCAA (Clavien, CCI) and to externally validate the St Antoine criteria for the selection of patients for DCS.
INTRODUCTION Acute appendicitis (AA) is still currently one of the most common digestive emergencies and appendectomy remains the reference treatment for AA  (1, 2). Uncomplicated AA (UCAA) is a disease of young people in good general condition treated by appendicectomy, mostly performed by laparoscopy, with a short hospital stay and few postoperative complications. UCAA may therefore be a good indication for day case surgery (DCS). The feasibility of a length of stay (LOS) less 24 hours has been evaluated in several previous studies  (3) (4) (5) (6)  and a review of the literature  (7)  and DCS, which corresponds to an LOS less than 12 hours without overnight hospitalization, has also been recently validated  (5, (8) (9) (10) (11). The AppendAmbu trial (NCT01839435) was the only study on DCS (together with the study by Lefrancois et al.