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Immunotherapy with immune checkpoint inhibitors in colorectal cancer:what is the future beyond deficient mismatch-repair tumours?

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Gastroenterology Report 2020年第1期8卷 11-24,I0001页

作者： nicolas Huyghe Pamela Baldin Marc van den Eynde Institut de Recherche Clinique et Expe´rimentale(Pole MIRO) UCLouvainBrusselsBelgium Department of Pathology Cliniques Universitaires St-LucInstitut Roi Albert IIBrusselsBelgium Department of Medical Oncology Cliniques Universitaires St-LucInstitut Roi Albert IIBrusselsBelgium

Following initial success in melanoma and lung tumours,immune checkpoint inhibitors(ICIs)are now well recognized as a major immunotherapy treatment modality for multiple types of solid *** colorectal cancer(CRC),the small subset that is mismatch-repair-deficient and microsatellite-instability-high(dMMR/MSI-H)derive benefit from immunotherapy;however,the vast majority of patients with proficient MMR(pMMR)or with microsatellite stable(MSS)CRC do *** and the consensus molecular subtype classifications are promising biomarkers in predicting therapeutic efficacy in selected *** pMRR/MSS CRC,biomarkers are also needed to understand the molecular mechanisms governing immune reactivity and to predict their relationship to *** continuous development of such biomarkers would offer new perspectives and more personalized treatments by targeting oncological options,including ICIs,which modify the tumour-immune *** this review,we focus on CRC and discuss the current status of ICIs,the role of biomarkers to predict response to immunotherapy,and the approaches being explored to render pMMR/MSS CRC more immunogenic through the use of combined therapies.

关键词： colorectal cancer immunotherapy immune checkpoint inhibitors immune response immunoscore

Two-dimensional modeling of fine sediment transport with mixed sediment and consolidation: Application to the Gironde Estuary,France

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International Journal of Sediment Research 2021年第6期36卷 736-746页

作者： Sylvain Orseau nicolas Huybrechts Pablo Tassi Damien Pham van Bang Fabrice Klein Cerema Direction Technique Eau Mer et Fleuves Sorbonne Universités Université de Technologie de Compiégne CNRSFRE2012 RobervalCentre de Recherche Royallieu Electricité de France R&D Department Laboratoire d'Hydraulique Saint Venant (ENPC-EDF/R&D-CEREMA) 5. Centre Eau Terre et Environnement INRS-ETE 6. Grand Port Maritime de Bordeaux

In order to optimize ship navigation in the macrotidal Gironde Estuary, a recent project funded by the port of Bordeaux aims at better understand and forecast hydrodynamic and fine sediment transport within the estuary. In the framework of this project, a two-dimensional hydro-sedimentary model is built. The model includes hydrodynamic forcings, mixed-sediment transport, and consolidation processes. The harmonic analysis of the astronomical tides reveals a strong distortion of the tidal wave inducing the growth of overtide constituents and the non-significant effect of tide-surge interactions in annual-scale prediction. Depending on hydrological conditions, river discharge can considerably alter the model accuracy due to the migration of the turbidity maximum zone modifying the bottom *** with measurements shows the ability of the model to reproduce suspended-sediment concentrations in the central Estuary. Sensitivity of the model to sediment features has also been discussed in regard of suspended-sediment concentrations and fluid mud deposits. The model will be further coupled with ship squat predictions and a morphodynamic model.

关键词： Sediment transport Numerical modeling Mixed sediment Gironde Estuary Opentelemac

Anomalous moire pattern of graphene investigated by scanning tunneling microscopy： Evidence of graphene growth on oxidized Cu（111）

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Nano Research 2014年第1期7卷 154-162页

作者： nicolas Reckinger Eloise van Hooijdonk Frederic Joucken Anastasia V. Tyurnina Stephane Lucas Jean-Francois Colome~ Research Center in Physics of Matter and Radiation (PMR) University of Namur Rue de Bruxelles 6 1 B-5000 Namur Belgium

The growth of graphene on oriented （111） copper films has been achieved by atmospheric pressure chemical vapor deposition. The structural properties of as-produced graphene have been investigated by scanning tunneling microscopy. Anomalous moir6 superstructures composed of well-defined linear periodic modulations have been observed. We report here on comprehensive and detailed studies of these particular moir6 patterns present in the graphene topography revealing that, in certain conditions, the growth can occur on the oxygen-induced reconstructed copper surface and not directly on the oriented （111） copper film as expected.

关键词： graphene scanning tunnelingmicroscopy Cu(111) copper oxidation atmospheric pressurechemical vapor deposition

Australasian microtektites across the Antarctic continent: Evidence from the Sør Rondane Mountain range (East Antarctica)

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Geoscience Frontiers 2021年第4期12卷 202-214页

作者： Bastien Soens Matthias van Ginneken Stepan Chernonozhkin nicolas Slotte Vinciane Debaille Frank vanhaecke Herman Terryn Philippe Claeys Steven Goderis Analytical Environmentaland Geo-ChemistryVrije Universiteit BrusselPleinlaan 2BE-1050 BrusselsBelgium Laboratoire G-Time UniversitéLibre de Bruxelles 50Av.F.D.Roosevelt CP 160/02BE-1050 BrusselsBelgium Centre for Astrophysics and Planetary Science University of KentCT27NZCanterburyKentUnited Kingdom Atomic&Mass Spectrometry–A&MS Research Unit Department of ChemistryGhent UniversityCampus SterreKrijgslaan 281–S12BE-9000 GhentBelgium Electrochemical and Surface Engineering Vrije Universiteit BrusselPleinlaan 2BE-1050 BrusselsBelgium

The~790 ka Australasian(micro)tektite strewn field is one of the most recent and best-known examples of impact ejecta emplacement as the result of a large-scale cratering event across a considerable part of Earth's surface(>10%in area).The Australasian strewn field is characterized by a tri-lobe pattern consisting of a large central distribution lobe,and two smaller side lobes extending to the west and ***,we report on the discovery of microtektite-like particles in sedimentary traps,containing abundant micrometeorite material,in the Sør Rondane Mountain(SRM)range of East *** thirty-three glassy particles display a characteristic pale yellowcolor and are predominantly spherical in shape,except for a single dumbbell-shaped *** vitreous spherules range in size from220 to 570μm,with an average diameter of~370μ*** compares relatively well with the size distribution(75–778μm)of Australasian microtektites previously recovered from the TransantarcticMountains(TAM)and located ca.2500–3000 km fromthe *** addition,the chemical composition of the SRM particles exhibits limited variation and is nearly identical to the‘normal-type’(i.e.,<6%MgO)TAM *** Sr and Nd isotope systematics for a single batch of SRM particles(n=26)strongly support their affiliation with TAMmicrotektites and the Australasian tektite strewn field in ***,Sr isotope ratios and Nd model ages suggest that the target material of the SRM particles was composed of a plagioclase-or carbonate-rich lithology derived from a Paleo-or Mesoproterozoic crustal *** affiliation to the Australasian strewn field requires long-range transportation,with estimated great circle distances of ca.11,600 km from the hypothetical source crater,provided transportation occurred along the central distribution *** is in agreement with the observations made for the Australasian microtektites recovered from Victoria Land(ca.11,000 km)and Larkman Nunatak(ca.12,000 km),w

关键词： Impact cratering Impact ejecta Target stratigraphy Volatilization Antarctica Microtektites

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Effect of self-weight consolidation on a hydro-sedimentological model for the Río de la Plata estuary

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International Journal of Sediment Research 2019年第5期34卷 444-454页

作者： Pablo Santoro Mónica Fossati Pablo Tassi nicolas Huybrechts Damien Pham van Bang Ismael Piedra-Cueva Instituto de Mecánica de los Fluidos e Ingeniería Ambiental Facultad de Ingeniería Universidad de la República Université Paris-Est Laboratory for Hydraulics Saint-Venant (ENPC-EDF/R& D-CEREMA) Electricity of France R&D Department Sorbonne Universités Université de Technologie de Compiègne FRE UTC-CNRS 3023 Roberval Centre de Recherche Royallieu Cerema Direction Technique Eau Mer et Fleuves Institut National de la Recherche Scientifique Centre-Eau Terre Environnement

The effect of the consolidation process on the morphodynamics and fine sediment dynamics of the Río de la Plata estuary is explored through a circulation-wave-sediment transport model. The consolidation model is calibrated based on settling column experimental data. Different simulations are done in order to initialize the mud layer distribution and to investigate the impact of different erosion parameter assumptions on the modeled sediment dynamics. Finally a two-year simulation is done with and without the consolidation process and realistic hydrodynamic forcings. Considering the consolidation process, the model correctly reproduces measured vertical density profiles in the Montevideo Bay access channel. The simulated suspended sediment dynamics behavior in Montevideo Bay with the consolidation process provides a more realistic deposition pattern in regard to the dredging activities.

关键词： Cohesive sediment Self-weight consolidation Morphodynamics Numerical modeling

Defective recovery of QT dispersion following transcatheter aortic valve implantation： frequency, predictors and prognosis

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Journal of Geriatric Cardiology 2015年第5期12卷 482-488页

作者： Rutger-Jan Nuis Gokhan Turgut Robert M van der Boon nicolas M van Mieghem Sjoerd T Nauta Patrick W Serruys Ron T van Domburg Giulio Zuchelli Luc Jordaens Peter P de Jaegere Department of Cardiology Erasmus University Medical Center Rotterdam the Netherlands Department of Electrophysiology Erasmus Thoraxcenter Rotterdam the Netherlands Department of Biostatistics Erasmus Thoraxeenter Rotterdam the Netherlands Division of Cardiovascular Diseases Azienda Ospedaliero-Universitaria Pisana Pisa Italy

Background Corrected QT dispersion （cQTD） has been correlated with non-uniform ventricular repolarisation and increased mortality. In patients with aortic stenosis, cQTD has been shown improved after surgical valve replacement, but the effects of transcatheter aortic valve implantation （TAVI） are unknown. Therefore, we sought to explore the frequency, predictors and prognostic effects of defective cQTD recovery at 6 months after TAVI. Methods A total of 222 patients underwent TAVI with the Medtronic-CoreValve System between November 2005 and January 2012. Patients who were on class Ⅰ or Ⅲ antiarrhythmics or on chronic haemodialysis or who developed atrial fibrillation, a new bundle branch block or became pacemaker dependent after TAVI were excluded. As a result, pre-, post- and follow-up ECG （median： 6 months） analysis was available in 45 eligible patients. Defective cQTD recovery was defined as any progression beyond the baseline cQTD at 6 months. Results In the 45 patients, the mean cQTD was 47 ± 23 ms at baseline, 45 ±17 ms immediately after TAVI and 40 ± 16 ms at 6 months （15% reduction, P = 0.049）. Compared to baseline, cQTD at 6 months was improved in 60% of the patients whereas defective cQTD recovery was present in 40%. cQTD increase immediately after TAVI was an independent predictor of defective cQTD recovery at 6 months （per 10 ms increase; OR： 1.89, 95% CI： 1.15-3.12）. By univariable analysis, defective cQTD recovery was associated with late mortality （HR： 1.52, 95% CI： 1.05-2.17）. Conclusions Despite a gradual reduction ofcQTD after TAVI, 40% of the patients had defective recovery at 6 months which was associated with late mortality. More detailed ECG analysis after TAVI may help to avoid late death.

关键词： Aortic stenosis Conduction abnormalities Left bundle branch block Predictors QT dispersion Transcatheter aortic valve implantation

Fast and reliable identification of atomically thin layers of TaSe2 crystals

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Nano Research 2013年第3期6卷 191-199页

作者： Andres Castellanos-Gomez Efren Navarro-Moratalla Guillermo Mokry Jorge Quereda Elena Pinilla-Cienfuegos nicolas Agrait Herre S. J. van der Zant Eugenio Coronado Gary A. Steele Gabino Rubio-Bollinger Kavli Institute of Nanoscience Delft University of Technology Lorentzweg 1 2628 CJ Delft The Netherlands Instituto Ciencia Molecular (ICMol) Univ. Valencia C/Catedrdtico Jose Beltrdn 2 E-46980 Paterna Spain Departamento de Fisica de la Materia Condensada (C-III). UniversidadAutonoma de Madrid Campus de Cantoblanco 28049 Madrid Spain Instituto Madrileno de Estudios Avanzados en Nanociencia IMDEA-Nanociencia E-28049 Madrid Spain

Deposition of clean and defect-free atomically thin two-dimensional crystalline flakes on surfaces by mechanical exfoliation of layered bulk materials has proven to be a powerful technique, but it requires a fast, reliable and non-destructive way to identify the atomically thin flakes among a crowd of thick flakes. In this work, we provide general guidelines to identify ultrathin flakes of TaSe2 by means of optical microscopy and Raman spectroscopy. Additionally, we determine the optimal substrates to facilitate the optical identification of atomically thin TaSe2 crystals. Experimental realization and isolation of ultrathin layers of TaSe2 enables future studies on the role of the dimensionality in interesting phenomena such as superconductivity and charge density waves.

关键词： atomically thin layer metal dichalcogenide layered superconductor TaSe2 optical microscopy Raman spectroscopy

Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis

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Journal of Geriatric Cardiology 2018年第4期15卷 261-267页

作者： Marjo JAG De Ronde-Tillmans Tom AJ de Jager Jeannette A Goudzwaard Nahid El Faquir nicolas M van Mieghem Felix Zijlstra Elisabeth MWJ. Utens Francesco US Mattace-Raso MaRie J Lenzen Peter PT de Jaegere Erasmus Medical Center Department of Cardiology Thorax Center Rotterdam the Netherlands Erasmus Medical Center Section of Geriatrics Department of Internal Medicine Rotterdam the Netherlands Erasmus Medical Center Department of Child and Adolescent Psychiatry/Psychology Sophia Children 's Hospital Rotterdam the Netherlands The Netherlands Research Institute of Child Development and Education University of Amsterdam the Netherlands

Background Transcatheter aortic valve implantation （TAVI） has become the standard treatment for patients with severe symptomatic aortic stenosis （AS） considered at very high risk for surgical aortic valve replacement. The purpose of this sub-study was to evaluate long-term （〉 4 years） health-related quality of life （QoL） in octogenarians who underwent TAVI. Methods A single center observational registry in twenty patients who underwent frame analysis assessment ≥ 4 years after TAVI. Health-related QoL was evaluated, using the Short Form-36 （SF-36）, the EuroQoL-5D （EQ-5D） and the visual analogue score （EQ-VAS） questionnaires. Results The mean SF-36 subscale scores at follow-up were physical functioning 40.8 ± 26.3, role physical functioning 67.7 ± 34.9, vitality 54.6 ± 21.6, general health 52.1 ± 20.4, social functioning 63.8 ± 37.7, role emotional functioning 70.2 ± 36.0, mental health 73.2 ± 23.3 and bodily pain 80.9 ± 22.9. The mean EQ-VAS score 〉 4 years after TAVI was 64.7 ± 15.1. With respect to functional class, 80% of the patients were in NYHA class I/II at follow-up compared to 15% prior to TAVI. Conclusions This sub-study reports a significant improvement in functional class （NYHA） in a selected group of very elderly patients 〉 4 years after TAVI. Furthermore, all patients showed a satisfactory QoL despite their age and multiple comorbidities. In addition, our study reveals a lower QoL when compared with the general age matched Dutch population.

关键词： Octogenarians Quality of life Transcatheter aortic valve implantation

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Prevalence and Correlates of Glucose Homeostasis Abnormalities in the Far-North Region Cameroon

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Open Journal of Preventive Medicine 2018年第1期8卷 6-20页

作者： Daniel Lemogoum William Ngatchou Elysée Claude Bika Lele Pierre Amta Philippe van de Borne Marc Leeman Philippe Donnen nicolas nicolas Preumont Jean Paul Degaute Michel Michel Hermans Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon ULB-Erasme Hospital Free Brussels University Brussels Belgium Cameroon Heart Foundation Douala Cameroon Medical Research Centre Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon School of Public Health Free Brussels University Brussels Belgium Endocrinology and Nutrition Unit Cliniques Universitaires St-Luc Université Catholique de Louvain Brussels Belgium

Background: Evidence indicates a growing burden of glucose homeostasis abnormalities (namely type 2 diabetes mellitus (T2DM) and prediabetes) in Cameroun. The aim of this study was to assess the prevalence and correlates of glucose homeostasis abnormalities (GHA) in the Far-North region of Cameroon, where these variables have not been explored so far. Methods: We included in this population-based cross-sectional survey 461 participants living urban area (Maroua) and 428 dwellers living in rural area (Tokombere) aged at least 18 years, using a multistage-cluster sampling frame. In all participants, we recorded sociodemographic, medical history, clinical data and fasting blood (capillary) glucose (FBG). Diabetes was considered for FBG ≥ 126 mg/dL or being on glucose-lowering medications, and impaired fasting glycemia (IFG) for FBG 100 - 125 mg/dL. Results: The overall age-standardized prevalence of GHA, IFG and diabetes was 33.6%, 21.7% and 11.9%, respectively. Those data were similar between urban and rural areas. Determinants of GHA were age, overweight/obesity, abdominal obesity and hypertension. IFG was only related to abdominal obesity, while diabetes was related to age, family history of diabetes, overweight/obesity, abdominal obesity and hypertension. Conclusion: Glucose homeostasis abnormalities are alarmingly high in Far North Cameroon. Efforts are needed to promote healthier lifestyles and initiate diabetes-screening campaigns in Cameroon.

关键词： Glucose Homeostasis Abnormalities Diabetes Prediabetes Far-North Region Cameroon Urban Rural