179 results on '"L, Bouwens"'
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2. De Toekomst van Gezond en Veilig Werken. Een brede horizonscan
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W van der Torre, M Lammers, K Oude Hengel, W ter Burg, L Bouwens, C Bekker, H van de Ven, M van der Noordt, L van Dam, P Eijsink, J de Lange, C Couwenbergh, S van Oostrom, W van der Torre, M Lammers, K Oude Hengel, W ter Burg, L Bouwens, C Bekker, H van de Ven, M van der Noordt, L van Dam, P Eijsink, J de Lange, C Couwenbergh, and S van Oostrom
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RIVM rapport:De wereld van werk verandert snel. Het ministerie van Sociale Zaken en Werkgelegenheid (SZW(Sociale zaken en werkgelegenheid)) wil daarom weten welke ontwikkelingen de komende twintig jaar belangrijk zijn voor gezond en veilig werken. Het RIVM en TNO hebben daarom verkend welke ontwikkelingen op Nederland afkomen en wat die betekenen voor gezond en veilig werken. De verkenning laat zien dat verschillende ontwikkelingen invloed gaan hebben op gezond en veilig werken. Voorbeelden zijn een vergrijsde beroepsbevolking, globalisering, individualisering, robotisering, de energietransitie en de toename van regels (juridisering). Alle ontwikkelingen staan niet op zichzelf, maar hangen met elkaar samen. RIVM en TNO hebben de verwachte gevolgen van die ontwikkelingen op gezond en veilig werken in kaart gebracht. Daarnaast zijn er vijf strategische thema’s benoemd. Zo geven veel technologische ontwikkelingen zowel kansen als bedreigingen voor gezond en veilig werken. De invloed op gezond en veilig werken is nu nog onduidelijk, omdat het er van afhangt hoe technologieën worden ingezet. Een tweede thema is dat de mentale belasting van werkenden waarschijnlijk groter wordt. Dit komt onder meer door de combinatie van werk met zorgtaken en een hoge werkdruk door bijvoorbeeld personeelstekorten. Een derde thema is dat de autonomie van werkenden verandert. Deze kan afnemen door juridisering, of als technologie het werk eentoniger maakt. Maar de autonomie kan juist toenemen door hybride werken, of als technologie het werk uitdagender maakt. Een vierde thema is dat werkenden moeten blijven ‘leren’. Dat komt omdat werktaken snel kunnen veranderen door onder meer nieuwe technologieën en de energietransitie. Ten vijfde stapelt het aantal risico’s zich op bij kwetsbare groepen werkenden, zoals flexwerkers en werkenden met een lager inkomen. Nieuwe risico’s, zoals de blootstelling aan hogere temperaturen tijdens werk en langdurig werken op grote hoogte, treffen waarschijnlijk deze groepen w, The world of work is changing rapidly. To understand the impact on occupational health and safety over the next 20 years, the Dutch Ministry of Social Affairs and Employment (SZW) commissioned RIVM and TNO to gain insight in the external future developments and their impact on health and safety at work. The project revealed a range of developments that will influence occupational health and safety. The ageing workforce, globalisation, growing individualism, robotisation, the energy transition and the proliferation of rules (juridification) are some examples of these developments. Most of these developments are interconnected in their occurrence and impact. RIVM and TNO qualitatively investigated the expected impact of these future developments on occupational health and safety. They also identified five strategic themes. The first theme concerns technology. Many technological developments present both opportunities and threats to occupational health and safety. The future impact remains unclear, as this depends on how technologies will be applied and used. Another theme is the increasing mental workload on workers as a result of combining work with care responsibilities, as well as more psychosocial workload due to -among others- staff shortages. The third theme is the changing autonomy of workers. On the one hand, autonomy may diminish as a result of juridification or as technology makes work tasks more monotonous. On the other hand, the flexibility to choose where and when to work (hybrid working) or the application of complex technologies that make work more challenging could increase autonomy. The fourth theme is the need for workers to continue to learn as work tasks change due to new technologies or the energy transition. The fifth theme is that vulnerable groups of workers, such as workers with a flexible contract or low income, face multiple risks, including physical workload, exposure to existing and novel substances, and increased job insecurity. This hori
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- 2023
3. Thuiswerkers in tijden van de COVID-19-pandemie
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Debby G. J. Beckers, L. Bouwens, Karen M Oude Hengel, Hardy A van de Ven, Wendela Hooftman, and T. Zoomer
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Social support ,McNemar's test ,media_common.quotation_subject ,Overtime ,Human factors and ergonomics ,Workload ,Burnout ,Descriptive research ,Psychology ,Autonomy ,Work, Health and Performance ,media_common ,Demography - Abstract
Working from home during COVID-19: a descriptive study on the changes in working conditions and health. This study provides an overview of the changes in working conditions and health of home workers in the Netherlands between 2019 (pre COVID-19) and July 2020 (during the COVID-19 pandemic). Moreover, this descriptive study examined if these changes differ across different group of workers (i.e. gender, age, and taking care for (young) children). McNemar test, paired T-tests and a combination of T-tests and weighted deviation contrasts were used to examine differences between 2019 and 2020. In general, the results show a diverse pattern – with both some improvements as well as some deteriorations of working conditions and health – among home workers. First, compared to the pre-covid situation, during the pandemic respondents worked more overtime and less home workers experienced high autonomy. Furthermore, the majority of the home workers did not have an ergonomic workplace at home. The results also showed more sedentary behavior in 2020 compared to 2019. On the other hand, during the covid period, less respondents said to experience high workload or emotional job demands. Additionally, more home workers reported a good self-perceived general and physical health. Overall, the degree of burnout complaints, work-life imbalance and social support does not change between measurements. Personal characteristics seem to play a role in changes in health and working conditions. More women and workers with a temporary contract reported burn-out complaints during the covid-period than before, whereas the proportion of men reporting burn-out complaints slightly decreased. The proportion of women and parents with young children with high autonomy decreased. Additionally, more parents with young children experienced a work-life imbalance.
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- 2021
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4. Veranderingen in het welbevinden van werknemers tijdens de COVID-19-pandemie: een studie onder zorgpersoneel, onderwijspersoneel en verkopers
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Karen M Oude Hengel, L. Bouwens, I. Eekhout, Swenneke van den Heuvel, Wendela Hooftman, and T. Zoomer
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Organizational Behavior and Human Resource Management ,2019-20 coronavirus outbreak ,Social Psychology ,Coronavirus disease 2019 (COVID-19) ,Strategy and Management ,media_common.quotation_subject ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Art ,Humanities ,media_common - Abstract
Samenvatting De COVID-19-pandemie en de daarmee getroffen maatregelen zorgden in maart 2020 direct voor grote veranderingen. Er zijn signalen dat deze veranderingen een negatief effect hebben op het welbevinden. Sommige onderzoeken spreken dit echter tegen, met name die onder de werkende bevolking. Mogelijk pakt de pandemie voor sommige groepen juist gunstig uit en voor andere groepen minder, waardoor het totaalbeeld vertekend wordt. In dit onderzoek focussen we ons op drie beroepsgroepen waarvan bekend is dat de COVID-19-pandemie en bijbehorende maatregelen direct een effect hebben op hun werktaken en hoeveelheid werkzaamheden: zorgpersoneel, onderwijspersoneel en verkopers. Met behulp van GEE-analyses onderzoeken we of er sprake is van een significante afname in welbevinden en een verandering in werkfactoren en in hoeverre de werkfactoren gerelateerd zijn aan het welbevinden. Uit de resultaten blijkt dat er slechts op beperkte schaal sprake is van een afname in welbevinden. Er wordt alleen een verslechtering in burn-outklachten gezien bij zorgpersoneel en verkopers. Werkfactoren laten vooral een verandering in gunstige richting zien, met uitzondering van autonomie. Die is in al de onderzochte groepen gedaald. Hoewel we wel een relatie vonden tussen de onderzochte werkfactoren en burn-outklachten, kunnen we de ontwikkelingen in het welbevinden niet verklaren door de verandering in werkfactoren.
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- 2021
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5. A novel cell population in the healthy pancreas that shares characteristics with the most aggressive pancreatic cancer
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S. Martens, K. Coolens, M. Van Bulck, H. Madhloum, F. Esni, G. Leuckx, H. Heimberg, L. Bouwens, P. Jacquemin, D. De Paep, P. in't Veld, P. Lefesvre, F.X. Real, M. Rovira, and I. Rooman
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Hepatology ,Endocrinology, Diabetes and Metabolism ,Gastroenterology - Published
- 2021
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6. Adapting forces modeling and simulation applications for use on high performance computational systems.
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Christina L. Bouwens, Steven 'Boots' Barnes, David Pratt, and Peter Melim
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- 2010
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7. LMIRA: list-mode iterative reconstruction algorithm for SPECT
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L. Bouwens, Howard C. Gifford, R. A. J. O. Dierckx, Ignace Lemahieu, Michael A. King, and R. Van de Walle
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Nuclear and High Energy Physics ,Image quality ,Computer science ,Iterative method ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Iterative reconstruction ,law.invention ,Nuclear Energy and Engineering ,Sampling (signal processing) ,Projector ,law ,Radiance ,Point (geometry) ,Electrical and Electronic Engineering ,Projection (set theory) ,Algorithm - Abstract
The goal of this project is to investigate a new method for using list-mode data instead of binned projection data for single photon emission computed tomography (SPECT) reconstruction. List-mode acquisition was once standardly available for planar scintigraphy and is now becoming available for SPECT acquisition. The authors implemented maximum-likelihood iterative reconstruction with list-mode data for SPECT using a new projector/backprojector pair, which employs an intermediate stage to separate the source and camera specific components. In two dimensions, the intermediate stage is a circle surrounding the object. An emission radiance distribution is calculated at the circle from the estimate of the source distribution in the object. This leads to the probability that a photon, coming from the source distribution, leaves the circle surrounding the object at a certain point, going in a specific direction. The algorithm uses the emission radiance distribution to obtain the probabilities used in the iterative reconstruction method. The model takes into account distance-dependent resolution and nonuniform attenuation. Results illustrate how the individual steps of the algorithm work. The list-mode iterative reconstruction algorithm is compared to the standard MLEM iterative reconstruction method, which employs binned data. It is concluded that the finer sampling provided by list-mode data results in superior image quality. By using the intermediate stage, the authors obtained a structure that can very easily be adapted to different types of collimators and acquisition protocols.
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- 2001
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8. Resolution recovery for list-mode reconstruction in SPECT
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Ignace Lemahieu, Howard C. Gifford, Michael A. King, Rudi Dierckx, Rik Van de Walle, and L. Bouwens
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Iterative method ,Computer science ,Gaussian ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Iterative reconstruction ,Sensitivity and Specificity ,Collimated light ,law.invention ,symbols.namesake ,Signal-to-noise ratio ,law ,Approximation error ,Image Processing, Computer-Assisted ,Radiology, Nuclear Medicine and imaging ,Image resolution ,Tomography, Emission-Computed, Single-Photon ,Radiological and Ultrasound Technology ,business.industry ,Reproducibility of Results ,Collimator ,Noise ,symbols ,Artificial intelligence ,business ,Algorithm ,Algorithms - Abstract
The purpose of the study was to evaluate the resolution recovery in the list-mode iterative reconstruction algorithm (LMIRA) for SPECT. In this study we compare the performance of the proposed method with other iterative resolution recovery methods for different noise levels. We developed an iterative reconstruction method which uses list-mode data instead of binned data. The new algorithm makes use of a more accurate model of the collimator structure. We compared the SPECT list-mode reconstruction with MLEM, OSEM and RBI, all including resolution recovery. For the evaluation we used Gaussian shaped sources with different FWHM at three different locations and three noise levels. For these distributions we calculated the reconstructed images for a different number of iterations. The absolute error for the reconstructed images was used to evaluate the performance. The performance of all four methods is comparable for the sources located in the centre of the field of view. For the sources located out of the centre, the error of the list-mode method is significantly lower than that of the other methods. Splitting the system model into a separate object-dependent and detector-dependent module gives us a flexible reconstruction method. With this we can very easily adapt the resolution recovery to different collimator types.
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- 2001
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9. MRI guided segmentation and quantification of SPECT images of the basal ganglia: a phantom study
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Ignace Lemahieu, L. Bouwens, Stefaan Vandenberghe, Michel Koole, Koenraad Van Laere, R.V. de Walle, and Rudi Dierckx
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Computer science ,Gadolinium ,Health Informatics ,Image processing ,Basal Ganglia ,Imaging phantom ,Spect imaging ,Basal ganglia ,medicine ,Humans ,Gamma Cameras ,Radiology, Nuclear Medicine and imaging ,Segmentation ,Tomography, Emission-Computed, Single-Photon ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Phantoms, Imaging ,business.industry ,Resolution (electron density) ,Reproducibility of Results ,Technetium ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Computer Graphics and Computer-Aided Design ,Computer Vision and Pattern Recognition ,Nuclear medicine ,business ,Emission computed tomography - Abstract
Due to the limited resolution of single-photon emission computed tomography (SPECT) imaging devices, tissue interfaces are not well defined in the reconstructed image, even though resolution recovery techniques may be used during reconstruction. Therefore, segmentation of a particular region and quantification of the tracer uptake in that region is critical due to spillover effects, when based on the SPECT image only. In this study, we present two methods for quantification of tracer uptake in a SPECT image, defined by a matched high resolution structural magnetic resonance image. We show preliminary results of both techniques, when applied for quantifying regional uptake in the different compartments of a phantom simulating the basal ganglia. These results indicate that the quantification method, which takes into account the blurring by the SPECT imaging device, promises to be perform better in the presence of background activity.
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- 2001
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10. PET imaging using gamma cameras
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F De Winter, Yves D'Asseler, L. Bouwens, R. A. J. O. Dierckx, Ignace Lemahieu, Stefaan Vandenberghe, Michel Koole, and R. Van de Walle
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medicine.medical_specialty ,Computer science ,Physics::Medical Physics ,Health Informatics ,Image processing ,Iterative reconstruction ,Sensitivity and Specificity ,Coincidence ,law.invention ,Positron ,Fluorodeoxyglucose F18 ,law ,Image Processing, Computer-Assisted ,medicine ,Humans ,Scattering, Radiation ,Coincidence circuit ,Gamma Cameras ,Radiology, Nuclear Medicine and imaging ,Computer vision ,Medical physics ,Gamma camera ,Radiological and Ultrasound Technology ,Phantoms, Imaging ,business.industry ,3D reconstruction ,Signal Processing, Computer-Assisted ,Equipment Design ,Computer Graphics and Computer-Aided Design ,Computer Science::Computer Vision and Pattern Recognition ,Calibration ,Computer Vision and Pattern Recognition ,Artificial intelligence ,Tomography ,business ,Tomography, Emission-Computed - Abstract
This paper will review the recent advances and future developments in the field of coincidence imaging of positron emitters with a conventional Anger-type gamma camera. FDG imaging has shown high clinical importance in cardiology, neurology and especially oncology. Since access to full ring PET is mainly limited to university hospitals, there have been new developments allowing PET imaging on the standard Anger gamma camera. First the principles of coincidence imaging on a gamma camera will be reviewed. We will discuss the limitations of this technique, and the techniques used to partly overcome these limitations. The different configurations of the gamma camera operating in coincidence mode are pointed out. Different corrections for image degrading effects and reconstruction methods are evaluated in the final part.
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- 2001
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11. PACS and multimodality in medical imaging
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R. Van de Walle, K. Van Laere, Stefaan Vandenberghe, Yves D'Asseler, L. Bouwens, C. Van de Wiele, Ignace Lemahieu, R A Dierckx, and Michel Koole
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medicine.medical_specialty ,Modality (human–computer interaction) ,Modalities ,Similarity (geometry) ,business.industry ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Biomedical Engineering ,Biophysics ,Health Informatics ,Bioengineering ,computer.software_genre ,Multimodality ,Biomaterials ,Picture archiving and communication system ,Voxel ,Medical imaging ,Medicine ,Computer vision ,Medical physics ,Artificial intelligence ,Medical diagnosis ,business ,computer ,Information Systems - Abstract
A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other.
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- 2000
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12. Culture of adult human islet preparations with hepatocyte growth factor and 804G matrix is mitogenic for duct cells but not for beta-cells
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V. H. Lefebvre, T. Otonkoski, J. Ustinov, M. A. Huotari, D. G. Pipeleers, and L. Bouwens
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Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 1998
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13. Implementation of the Joint Analysis System on TOW to Enhance DoD Analysis Performance
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Peter Melim, Boots Barnes, David Pratt, Christina L. Bouwens, and Al Sweetser
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Program evaluation ,Parallel processing (DSP implementation) ,Computer science ,Operating system ,Code (cryptography) ,computer.software_genre ,Supercomputer ,Baseline (configuration management) ,computer ,Port (computer networking) ,Porting - Abstract
The Joint Analysis System (JAS) is a multi-sided, joint campaign-level simulation used by the Office of the Secretary of Defense/Director of Cost Assessment and Program Evaluation (OSD/CAPE) Simulation and Analysis Center (SAC) for theater-level strategic analysis to support and assist Department of Defense (DoD) decision-making. The need for a higher execution speed for JAS (400 times real-time) combined with a desire for the shortest possible time-to-solution has led to the application of high performance computers (HPCs) to support the JAS program goals. Previous work with JAS [previously called the Joint War fighting System (JWARS)] explored the viability of parallel execution of computationally-intensive simulation processes to shorten execution times. Further work was performed to port the "back-end" simulation code to the Linux® (Linus Torvalds) environment to take advantage of Linux-based HPC assets. Capabilities developed as part of the parallel processing effort are part of the JAS technical library, and the Linux porting is now part of baseline code. The US Army Research Laboratory (ARL) DoD Supercomputing Resource Center (DSRC) has recently added a 6,656 core SGI Altix® ICE 8200 system (called TOW) to its toolset. This new system offers the SAC an opportunity to further utilize the processing capabilities offered by HPCs. The focus of this paper is to discuss the challenges and lessons learned in adapting JAS for use on TOW.
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- 2010
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14. Resolution properties of triple-headed coincidence imaging
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R. Van de Walle, Ignace Lemahieu, R. A. J. O. Dierckx, Yves D'Asseler, Michel Koole, L. Bouwens, and Stefaan Vandenberghe
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Physics ,Full width at half maximum ,Photon ,Optics ,Angle of incidence (optics) ,business.industry ,Resolution (electron density) ,Detector ,Sensitivity (control systems) ,Radius ,business ,Coincidence - Abstract
Due to the rising interest in clinical PET imaging, some manufacturers adapt two-headed gamma cameras to work in coincidence mode. Recently, the use of three heads for coincidence imaging has been suggested. The three heads can be placed in different configurations to achieve optimal sensitivity profiles. Two of these configurations are U-shape and triangular. As the average angle of incidence of the photons will differ for each configuration, it is expected that the resolution properties will be different. Resolution will be degraded by angle of incidence effects, non-colinearity of the photons, and, for axial resolution, rebinning of the list mode data to two-dimensional projections. In this paper, we investigate the influence of camera configuration, detector radius and scatter medium on transaxial and axial resolution properties. FWHM and FWTM were measured for different values of these parameter, and compared with each other.
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- 2005
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15. Randoms correction for gamma camera based PET list-mode reconstruction
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R. A. J. O. Dierckx, Ignace Lemahieu, L. Bouwens, Stefaan Vandenberghe, Michel Koole, R. Van de Walle, and Y. D 'Asseler
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Physics ,business.industry ,Detector ,Mode (statistics) ,Solid angle ,Iterative reconstruction ,computer.software_genre ,List mode ,law.invention ,law ,Voxel ,Computer vision ,Artificial intelligence ,business ,computer ,Rotation (mathematics) ,Gamma camera - Abstract
Gamma cameras used in PET mode are operating at high count rates, which leads to a high number of randoms in the acquired data. These data are often stored in listmode format to obtain more accurate reconstructions. We propose a randoms correction for an iterative list mode based reconstruction, which is based on the single photon distribution on each detector head. The method takes the spatial variation of the random coincidences into account. From the singles rates on each head the number of randoms in each voxel of the reconstruction is estimated. This is done by integrating the product of the singles over the solid angle formed by the voxel and both detectors. Camera rotation is taken Into account by integration this over all detector angles. This method only requires a quick singles scan prior or after the acquisition when there is unknown activity outside the FOV. When there is no activity outside the FOV or it is known the singles distribution on the detector head can be estimated from the reconstructed images. The randoms distribution can be subtracted after the reconstruction has been done.
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- 2002
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16. MRI-guided quantification of SPECT-images of the basal ganglia: a phantom study
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R. A. J. O. Dierckx, K. Van Laere, Stefaan Vandenberghe, Ignace Lemahieu, Yves D'Asseler, L. Bouwens, R. T. Van de Walle, and Michel Koole
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Physics ,medicine.diagnostic_test ,business.industry ,Iterative reconstruction ,Image segmentation ,Single-photon emission computed tomography ,Imaging phantom ,Spect imaging ,Basal ganglia ,medicine ,Nuclear medicine ,business ,Image resolution ,Mri guided - Abstract
In this study, the authors present two methods for quantification of tracer uptake in a SPECT image, guided by a matched high-resolution structural MR image. The authors show preliminary results of both techniques, when applied for quantifying regional uptake in the different compartments of a phantom simulating the basal ganglia. These results indicate that the quantification method, which takes into account the blurring by the SPECT imaging device, promises to be more performant in the presence of background activity.
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- 2002
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17. LMIRA: list mode iterative reconstruction algorithm for SPECT
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L. Bouwens, R. Van de Walle, H. Gifford, M. King, I. Lemahieu, and R.A. Dierckx
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- 2002
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18. Separating the object and detector dependent characteristics of projector/backprojector through use of an intermediate stage
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Howard C. Gifford, R. A. J. O. Dierckx, L. Bouwens, Ignace Lemahieu, Michael A. King, and R. Van de Walle
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Physics ,Iterative method ,business.industry ,Detector ,Iterative reconstruction ,Object (computer science) ,Bin ,law.invention ,Projector ,law ,Point (geometry) ,Computer vision ,Sensitivity (control systems) ,Artificial intelligence ,business - Abstract
A new projector/backprojector pair for iterative reconstruction using an intermediate stage is proposed. The aim was to separate the object-dependent and the detector-dependent characteristics into two separate modules. In two-dimensions (2D) the intermediate stage is a circle surrounding the object. An emission distribution is calculated at the circle from the initial estimate of the source distribution in the object. This leads to the probability that a photon, coming from the source distribution, leaves the circle surrounding the object at a certain point, going in a specific direction. Iterative reconstruction uses the total system sensitivity calculated from the integration over the distribution and the individual sensitivity for a given bin location, derived from the integration over a fraction of the distribution. The fraction is calculated from the geometry of the detection system. This information can be used in the forward and backprojection of an iterative reconstruction method to obtain a more accurate model of the processes involved. By using the intermediate stage the authors obtained a structure that can very easily be adapted to different types of collimators, taking into account the distance dependent resolution, and acquisition protocols. The method can even be used for list-mode reconstruction.
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- 2002
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19. Resolution recovery for list-mode reconstruction in SPECT
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Howard C. Gifford, L. Bouwens, Ignace Lemahieu, Rik Van de Walle, Michael A. King, and Rudi Dierckx
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Physics ,business.industry ,Gaussian ,Resolution (electron density) ,Collimator ,Iterative reconstruction ,law.invention ,Noise ,symbols.namesake ,law ,Radiance ,symbols ,Computer vision ,Point (geometry) ,Artificial intelligence ,Projection (set theory) ,business - Abstract
We developed an iterative reconstruction method for SPECT which uses list-mode data instead of binned data. It uses a more accurate model of the collimator structure. The purpose of the study was to evaluate the resolution recovery and to compare its performance to other iterative resolution recovery methods in the case of high noise levels The source distribution is projected onto an intermediate layer. Doing this we obtain the complete emission radiance distribution as an angular sinogram. This step is independent of the acquisition system. To incorporate the resolution of the system we project the individual list-mode events over the collimator wells to the intermediate layer. This projection onto the angular sinogram will define the probability a photon from the source distribution will reach this specific location on the surface of the crystal, thus being accepted by the collimator hole. We compared the SPECT list-mode reconstruction to MLEM, OSEM and RBI. We used Gaussian shaped point sources with different FWHM at different noise levels. For these distributions we calculated the reconstructed images at different number of iterations. The modeling of the resolution in this algorithm leads to a better resolution recovery compared to other methods, which tend to overcorrect.
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- 2001
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20. Template-based scatter correction in clinical brain perfusion SPECT
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Rik Van de Walle, Rudi Dierckx, Yves D'Asseler, L. Bouwens, Koen Van Laere, Ignace Lemahieu, Stefaan Vandenberghe, and Michel Koole
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Physics ,Photon ,medicine.diagnostic_test ,Pixel ,business.industry ,Monte Carlo method ,Single-photon emission computed tomography ,law.invention ,Optics ,law ,Computer Science::Computer Vision and Pattern Recognition ,Spect imaging ,medicine ,business ,Projection (set theory) ,Correction for attenuation ,Gamma camera - Abstract
A practical method for scatter compensation in SPECT imaging is the triple energy window technique (TEW) which estimates the fraction of scattered photons in the projection data pixel by pixel. This technique requires an acquisition of counts in three windows of the energy spectrum for each projection bin, which is not possible on every gamma camera. The aim of this study is to set up a scatter template for brain perfusion SPECT imaging by means of the scatter data acquired with the triple energy window technique. This scatter template can be used for scatter correction as follows: the scatter template is realigned with the acquired, by scatter degraded and reconstructed image by means of the corresponding emssion template, which also includes scatter counts. The ratios between the voxelvalues of this emission template and the acquired and reconstructed image are used to locally adjust the scatter template. Finally the acquired and reconstructed image is corrected for scatter by substracting the thus obtained scatter estimates. We compared the template based approach with the TEW scatter correction technique for data acquired with same gamma camera system and found a similar performance for both correction methods.
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- 2001
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21. Separability of three-dimensional geometric sensitivity correction in triple-headed gamma camera systems
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Rik Van de Walle, L. Bouwens, Michel Koole, Stefaan Vandenberghe, Yves D'Asseler, Ignace Lemahieu, and Rudi Dierckx
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Photon ,business.industry ,Mathematical analysis ,Field of view ,Function (mathematics) ,Measure (mathematics) ,law.invention ,Optics ,law ,Position (vector) ,Sensitivity (control systems) ,business ,Rotation (mathematics) ,Mathematics ,Gamma camera - Abstract
Gamma camera PET (Positron Emission Tomography) offers a low-cost alternative for dedicated PET scanners. However, sensitivity and count rate capabilities of dual-headed gamma cameras with PET capabilities are still limited compared to full-ring dedicated PET scanners. To improve the geometric sensitivity of these systems, triple-headed gamma camera PET has been proposed. As is the case for dual-headed PET, the sensitivity of these devices varies with the position within the field of view (FOV) of the camera. This variation should be corrected for when reconstructing the images. In earlier work, we calculated the two-dimensional sensitivity variation for any triple-headed configuration. This can be used to correct the data if the acquisition is done using axial filters, which effectively limit the axial angle of incidence of the photons, comparable to 2D dedicated PET. More recently, these results were extended to a fully 3D calculation of the geometric sensitivity variation. In this work, the results of these calculations are compared to the standard approach to correct for 3D geometric sensitivity variation. Current implementations of triple-headed gamma camera PET use two independent corrections to account for three-dimensional sensitivity variations: one in the transaxial direction and one in the axial direction. This approach implicitly assumes that the actual variation is separable in two independent components. We recently derived a theoretical expression for the 3D sensitivity variation, and in this work we investigate the separability of our result. To investigate the separability of the sensitivity variations, an axial and transaxial profile through the calculated variation was taken, and these two were multiplied, thus creating a separable function. If the variation were perfectly separable, this function would be identical to the calculated variation. As a measure of separability, we calculated the percentual deviation of the separable function to the original variation. We investigated the separability for several camera configurations and rotation radii. We found that, for all configurations, the variation is not separable , and becomes less separable as the rotation radius tends to smaller values. This indicates that in this case, our sensitivity correction will give better results than the separable correction now applied.
- Published
- 2001
- Full Text
- View/download PDF
22. Image-correction techniques in SPECT
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Johan Nuyts, R. A. J. O. Dierckx, R. Van de Walle, L. Bouwens, Yves D'Asseler, Stefaan Vandenberghe, Ignace Lemahieu, and Michel Koole
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Photon ,Image quality ,Monte Carlo method ,Health Informatics ,Iterative reconstruction ,Single-photon emission computed tomography ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Computer vision ,Computer Simulation ,Physics ,Tomography, Emission-Computed, Single-Photon ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Attenuation ,Detector ,Image Enhancement ,Computer Graphics and Computer-Aided Design ,Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Error detection and correction ,Monte Carlo Method ,Algorithms - Abstract
This overview takes a look at different correction techniques for Single Photon Emission Computed Tomography (SPECT). We discuss the influence of the detection system followed by the scatter and attenuation caused by the object of investigation. When possible we describe how the correction methods for the different physical effects can be incorporated in the reconstruction method, being either filtered backprojection or iterative reconstruction.
- Published
- 2001
23. Nonuniform transmission in brain SPECT using 201Tl, 153Gd, and 99mTc static line sources: anthropomorphic dosimetry studies and influence on brain quantification
- Author
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K, Van Laere, M, Koole, T, Kauppinen, M, Monsieurs, L, Bouwens, and R, Dierck
- Subjects
Adult ,Radioisotopes ,Tomography, Emission-Computed, Single-Photon ,Thallium Radioisotopes ,Phantoms, Imaging ,Image Processing, Computer-Assisted ,Brain ,Humans ,Technetium ,Gadolinium ,Radiation Dosage - Abstract
Nonuniform attenuation correction in brain SPECT can be done routinely by means of additional gamma transmission CT (TCT) measurements, using different commercially available line-source isotopes, 201Tl, 153Gd, and 99mTc are among the most commonly used isotopes, depending on practical and cost-effectiveness issues. We have measured additional radiation burden from static uncollimated brain SPECT transmission sources for these isotopes. The influence of the transmission isotope on brain quantification was also measured and compared with uniform attenuation correction for phantom and human data. Full iterative transmission and emission reconstruction were compared with filtered backprojection techniques.Rod sources with 201Tl, 153Gd, and 99mTc were used on a triple-head gamma camera. Dosimetry was performed using LiF TLD-100 pellets and an anthropomorphic RANDO phantom. Effective dose equivalents were calculated on the basis of measured and extrapolated absorbed doses. For brain activity measurements, a Hoffman phantom was used. Images were corrected for scatter (triple-energy window) and were reconstructed by Chang attenuation correction and filtered backprojection as well as full iterative reconstruction (ordered-subsets expectation maximization [OSEM]). To study the effect of inhomogeneous bone attenuation, realistic measurements were performed on 10 young, healthy volunteers with 153Gd TCT. After stereotactic image realignment, a volume-of-interest analysis normalized to total counts was performed.Brain SPECT-TCT using 201Tl, 153Gd, and 99mTc produced total effective dose-rate equivalents of 50.3 +/- 11.2, 32.0 +/- 2.7, and 71.1 +/- 7.1 microSv/GBq x h, respectively, representing dose equivalents of 18.6, 11.9, and 26.3 microSv for a typical 20-min brain SPECT scan at maximal used source strength. Standardized quantification resulted in insignificant differences between the isotopes and methods (Chang versus OSEM) used for nonuniform correction. Iterative reconstruction enhanced image contrast and provided more accurate gray-to-white matter ratios. Between nonuniform and uniform attenuation with an optimized attenuation coefficient, slight central discrepancies were found for volunteer studies. Significantly lower intersubject variation was found for nonuniform corrected values in infratentorial and posterior brain regions.Brain transmission scanning using 201Tl, 153Gd, or 99mTc results in limited effective radiation dose equivalents compared with the typical radiation burden. Relative brain perfusion quantification is not significantly different for the various nonuniform TCT isotopes. Iterative reconstruction improves gray-to-white contrasts but has no significant influence on brain perfusion semiquantification. Nonuniform attenuation correction decreases intersubject variability in the posterior brain regions that were compared, which may lead to improved sensitivity toward clinical applications.
- Published
- 2001
24. Iterative reconstruction algorithms in nuclear medicine
- Author
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L. Bouwens, Tomi Kauppinen, Michel Koole, Rudi Dierckx, K. Van Laere, Yves D'Asseler, Ignace Lemahieu, Stefaan Vandenberghe, and R. Van de Walle
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Time Factors ,Iterative method ,Image quality ,Physics::Medical Physics ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Streak ,Health Informatics ,Image processing ,Iterative reconstruction ,Single-photon emission computed tomography ,Acceleration ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Computer vision ,Computer Simulation ,Poisson Distribution ,Physics ,Tomography, Emission-Computed, Single-Photon ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Computer Graphics and Computer-Aided Design ,Computer Vision and Pattern Recognition ,Artificial intelligence ,Tomography ,Nuclear Medicine ,business ,Nuclear medicine ,Algorithm ,Algorithms ,Tomography, Emission-Computed - Abstract
Iterative reconstruction algorithms produce accurate images without streak artifacts as in filtered backprojection. They allow improved incorporation of important corrections for image degrading effects, such as attenuation, scatter and depth-dependent resolution. Only some corrections, which are important for accurate reconstruction in positron emission tomography and single photon emission computed tomography, can be applied to the data before filtered backprojection. The main limitation for introducing iterative algorithms in nuclear medicine has been computation time, which is much longer for iterative techniques than for filtered backprojection. Modern algorithms make use of acceleration techniques to speed up the reconstruction. These acceleration techniques and the development in computer processors have introduced iterative reconstruction in daily nuclear medicine routine. We give an overview of the most important iterative techniques and discuss the different corrections that can be incorporated to improve the image quality.
- Published
- 2001
25. Geometric sensitivity calculation of three-headed gamma-camera-based coincidence detection
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L. Bouwens, Ignace Lemahieu, Rik Van de Walle, Stefaan Vandenberghe, Yves D'Asseler, Michel Koole, and Rudi Dierckx
- Subjects
Physics ,Optics ,Planar ,business.industry ,Position (vector) ,Detector ,Perpendicular ,Field of view ,Geometry ,Sensitivity (control systems) ,Equilateral triangle ,business ,Coincidence - Abstract
In the near future, it will be possible to perform coincidence detection on a gamma camera with three heads, which increases the geometric sensitivity of the system. Different geometric configurations are possible, and each configuration yields a different geometric sensitivity. The purpose of this work was to calculate the sensitivities for different three-headed configurations as a function of the position in the field of view, the dimensions of the detector heads and the distance of the heads from the center of the field of view. The configurations that were compared are: a regular two headed configuration (180 deg. opposed), a triple-headed configuration with the three heads in an equilateral triangle (120 deg.), and a triple-headed configuration with two heads in a regular two headed configuration, and the third perpendicular between the first two, which makes a U-shaped configuration. An expression was derived for any planar detector configuration to calculate the geometric sensitivity for each Line Of Response (LOR). This sensitivity was integrated to get the sensitivity profile, which gives the geometric sensitivity at a certain distance from the center of rotation. We found that the triangular configuration gave the best sensitivities when placed very near to each other (nearly full ring configuration), but for larger fields of view, the U-shaped configuration performed better.
- Published
- 2000
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26. [Neogenesis of beta cells and islet formation]
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L, Bouwens
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Adult ,Islets of Langerhans ,Infant, Newborn ,Humans ,Regeneration ,Cell Division - Published
- 2000
27. Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells
- Author
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M, Roivainen, S, Rasilainen, P, Ylipaasto, R, Nissinen, J, Ustinov, L, Bouwens, D L, Eizirik, T, Hovi, and T, Otonkoski
- Subjects
Adult ,Cell Survival ,Coxsackievirus Infections ,Nitric Oxide Synthase Type II ,Apoptosis ,DNA ,DNA Fragmentation ,Virus Replication ,Immunohistochemistry ,Islets of Langerhans ,Microscopy, Electron ,In Situ Nick-End Labeling ,Humans ,Insulin ,RNA, Messenger ,Nitric Oxide Synthase ,Enterovirus - Abstract
Enteroviruses may be involved in the pathogenesis of insulin-dependent diabetes mellitus, either through direct beta-cell infection or as triggers of autoimmunity. In the present study we investigated the patterns of infection in adult human islet cell preparations (consisting of 56+/-14% beta-cells) by several coxsackieviruses. The cells were infected with prototype strains of coxsackievirus B (CBV) 3, 4, and 5 as well as coxsackievirus A9 (CAV-9). The previously characterized diabetogenic strain of coxsackievirus B4 (CBV-4-E2) was used as a reference. All viruses replicated well in beta-cells, but only CBVs caused cell death. One week after infection, the insulin response of the beta-cells to glucose or glucose plus theophylline was most severely impaired by CBV-3 and CBV-5 infections. CBV-4 also caused significant functional impairment, whereas CAV-9-infected cells responded like uninfected controls. After 2 days of infection, about 40% of CBV-5-infected cells had undergone morphological changes characteristic of pyknosis, i.e. highly distorted nuclei with condensed but intact chromatin. Both mitochondria and plasma membrane were intact in these cells. DNA fragmentation was found in 5.9+/-1.1% of CBV-5-infected beta-cell nuclei (2.1+/-0.3% in controls; P0.01). CAV-9 infection did not induce DNA fragmentation. One week after infection the majority of infected cells showed characteristics of secondary necrosis. Medium nitrite and inducible nitric oxide synthase messenger ribonucleic acid levels were not significantly up-regulated by CBV infection. These results suggest that several enteroviruses may infect human beta-cells. The infection may result in functional impairment or death of the beta-cell or may have no apparent immediate adverse effects, as shown here for CAV-9. Coxsackie B viruses cause functional impairment and beta-cell death characterized by nuclear pyknosis. Apoptosis appears to play a minor role during a productive CBV infection in beta-cells.
- Published
- 2000
28. Effect of interferon-gamma and glucose on major histocompatibility complex class I and class II expression by pancreatic beta- and non-beta-cells
- Author
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D, Pavlovic, M, van de Winkel, B, van der Auwera, M C, Chen, F, Schuit, L, Bouwens, and D, Pipeleers
- Subjects
Adult ,Male ,Adolescent ,Histocompatibility Antigens Class I ,Histocompatibility Antigens Class II ,Middle Aged ,Flow Cytometry ,Immunohistochemistry ,Rats ,Interferon-gamma ,Islets of Langerhans ,Glucose ,Animals ,Humans ,Keratins ,Rats, Wistar ,Fluorescent Antibody Technique, Indirect ,beta 2-Microglobulin ,Pancreas - Abstract
Surface major histocompatibility complex (MHC) class I and class II expression by pancreatic islet cells is considered a local initiator or regulator of immune processes that can lead to diabetes. Locally released cytokines, in particular interferon-gamma, are known to stimulate MHC antigen expression by islet cells. The present study quantifies MHC expression in cultured pancreatic beta- and non-beta-cells from both rat and human organs. Interferon-gamma increased MHC class I expression in endocrine beta- and non-beta-cells as well as in pancreatic ductal cells. The cytokine induced a 6-fold increase in the MHC class I messenger ribonucleic acid levels in pancreatic beta-cells; this effect was 2-fold amplified in the presence of elevated glucose levels (20 mmol/L instead of 6 mmol/L). No MHC class II expression was observed in endocrine beta- or non-beta-cells; human, but not rat, ductal cells exhibited MHC class II expression that increased in the presence of interferon-gamma. These data indicate that the increase in beta-cell MHC class I expression described in the pancreata of diabetic patients may result from stimulated transcription after exposure to locally released interferon-gamma and/or to a hyperglycemic state. The association of human islets with ductal cells in which MHC class II expression is stimulated by interferon-gamma makes these cells potential participants in the autoimmune process in diabetes.
- Published
- 1997
29. Effect of vascular endothelial growth factor on growth and differentiation of pancreatic ductal epithelium
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I, Rooman, F, Schuit, and L, Bouwens
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Male ,Vascular Endothelial Growth Factor A ,Lymphokines ,Vascular Endothelial Growth Factors ,Pancreatic Ducts ,Epithelial Cells ,Endothelial Growth Factors ,Immunohistochemistry ,Epithelium ,Rats ,Islets of Langerhans ,Pancreatitis ,Animals ,Rats, Wistar ,Ligation ,Cell Division ,Cells, Cultured - Abstract
Endocrine and exocrine pancreatic morphogenesis is known to occur from ductal epithelium, but the factors that regulate this process are unknown. Vascular endothelial growth factor (VEGF)/vascular permeability factor has recently been reported to affect fetal islet ontogenesis. VEGF is an angiogenic factor with a growth-promoting effect that is thought to be restricted to vascular endothelial cells. We demonstrated that VEGF is also a mitogen for adult rat pancreatic duct epithelial cells in primary culture. VEGF supplementation to a serum-free culture medium increased the 5-bromo-2'-deoxyuridine-pulse labeling index of ductal cells more than 2-fold. Immunohistochemical staining and protein blots revealed that pancreatic duct cells express fetal liver kinase-1 high-affinity receptors for VEGF. In pancreatic tissue, immunohistochemistry shows that VEGF peptide is expressed in normal pancreatic islet cells. In duct ligation-induced acute pancreatitis, numerous inflammatory leukocytes containing VEGF were seen to infiltrate between hyperplastic ducts. In the latter model, islet neogenesis has previously been observed. Our data indicate the possibility that VEGF plays a role in the paracrine regulation of ductal growth and differentiation in vivo, eg, in pancreatitis. In vitro, however, VEGF did not induce endocrine differentiation of ductal cells, indicating that it is not the only factor required for the activation of islet neogenesis.
- Published
- 1997
30. SPECT VISUALISATION OF FLOW THROUGH ARTIFICIAL ORGANS
- Author
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Sunny Eloot, D De Wachter, L. Bouwens, Pascal Verdonck, B Cuvelier, Pw Dierickx, and Rudi Dierckx
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Biomaterials ,Flow (mathematics) ,business.industry ,Biomedical Engineering ,Biophysics ,Medicine ,Bioengineering ,General Medicine ,business ,Biomedical engineering ,Visualization - Published
- 2000
- Full Text
- View/download PDF
31. PACS and multimodality in medical imaging.
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Y. D'Asseler, M. Koole, K. Van Laere, S. Vandenberghe, L. Bouwens, R. Van de Walle, C. Van de Wiele, I. Lemahieu, and R.A. Dierckx
- Subjects
PICTURE archiving & communication systems ,BRAIN ,DIAGNOSTIC imaging ,MEDICAL imaging systems - Abstract
A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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32. Late abstracts 186–187
- Author
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J. Jaehne, H. -J. Meyer, Ch. Wittekind, H. Maschek, R. Pichlmayr, G. Jacobi, G. Weiermann, H. Gräfin Vitzthum, D. Schwabe, Ch. Manegold, B. Krempien, M. Kaufmann, M. Bailly, J. -F. Doré, Ø. Fodstad, I. Kjønniksen, A. Brøgger, V. A. Flørenes, A. Pihl, S. Aamdal, J. M. Nesland, A. A. Geldof, B. R. Rao, C. De Giovanni, P. -L. Lollini, B. Del Re, K. Scotlandi, G. Nicoletti, P. Nanni, G. N. P. Van Muijen, J. M. Van Der Wiel-Miezenbeek, L. M. H. A. Cornelissen, C. F. J. Jansen, D. J. Ruiter, J. Kieler, Y. Oda, Y. Tokuriki, E. M. Tenang, J. F. Lamb, E. Galante, F. Zanoni, D. Galluzzi, A. Cerrotta, G. Martelli, A. Guzzon, D. Reduzzi, E. Barberá-Guillem, J. R. Barceló, B. Urcelay, A. I. Alonso-Varona, F. Vidal-Vanaclocha, I. D. Bassukas, B. Maurer-Schultze, R. Storeng, C. Manzotti, G. Pratesi, G. Schachert, I. J. Fidler, I. A. Grimstad, G. Th. Rutt, P. Riesinger, J. Frank, G. Neumann, J. H. Wissler, G. Bastert, W. Liebrich, B. Lehner, S. Gonzer, P. Schlag, K. Vehmeyer, T. Hajto, H. -J. Gabius, I. Funke, G. Schlimok, B. Bock, A. Dreps, B. Schweiberer, G. Riethmüller, U. Nicolai, K. -F. Vykoupil, M. Wolf, K. Havemann, A. Georgii, S. Bertrand, M. -J. N'Guyen, J. Siracky, B. Kysela, E. Siracka, E. Pflüger, V. Schirrmacher, M. D. Boyano, N. Hanania, M. F. Poupon, G. V. Sherbet, M. S. Lakshmi, F. Van Roy, K. Vleminckx, W. Fiers, C. Dragonetti, G. De Bruyne, L. Messiaen, M. Mareel, S. Kuhn, H. Choritz, U. Schmid, H. Bihl, A. Griesbach, S. Matzku, S. A. Eccles, H. P. Purvies, F. R. Miller, D. McEachern, A. Ponton, C. Waghorne, B. Coulombe, R. S. Kerbel, M. Breitman, D. Skup, M. C. Gingras, L. Jarolim, J. A. Wright, A. H. Greenberg, M. J. N'Guyen, G. Allavena, A. Melchiori, O. Aresu, M. Percario, S. Parodi, J. Schmidt, P. Kars, G. Chader, A. Albini, M. Zöller, J. C. Lissitzky, M. Bouzon, P. M. Martin, I. M. Grossi, J. D. Taylor, K. V. Honn, B. Koch, W. Baum, J. Giedl, H. J. Gabius, J. R. Kalden, A. A. Hakim, A. LadÁnyi, J. Timár, E. Moczar, K. Lapis, K. Müller, M. F. Wolf, B. Benz, K. Schumacher, W. Kemmner, J. Morgenthaler, R. Brossmer, B. Hagmar, G. Burns, L. J. Erkell§, W. Ryd, S. Paku, A. Rot, E. Hilario, F. Unda, J. Simón, S. F. Aliño, N. S. E. Sargent, M. M. Burger, P. Altevogt, A. Kowitz, H. Chopra, G. Bandlow, G. A. Nagel, R. Lotan, D. Carralero, D. Lotan, A. Raz, A. P. N. Skubitz, G. G. Koliakos, L. T. Furcht, A. S. Charonis, A. Hamann, D. Jablonski-Westrich, P. Jonas, R. Harder, E. C. Butcher, H. G. Thiele, F. Breillout, E. Antoine, V. Lascaux, H. -J. Boxberger, N. Paweletz, M. Bracke, B. Vyncke, G. Opdenakker, V. Castronovo, J. -M. Foidart, M. Camacho, A. Fabra Fras, A. Llorens, M. L. Rutllant, L. J. Erkell, G. Brunner, A. Heredia, J. M. Imhoff, P. Burtin, M. Nakajima, J. Lunec, C. Parker, J. A. Fennelly, K. Smith, F. F. Roossien, G. La Rivière, E. Roos, M. Erdel, G. Trefz, E. Spiess, W. Ebert, S. Verhaegen, L. Remels, H. Verschueren, D. Dekegel, P. De Baetselier, D. Van Hecke, E. Hannecart-Pokorni, K. H. Falkvoll, A. Alonso, A. Baroja, U. Sebbag, E. Barbera-Guillem, J. Behrens, M. M. Mareel, W. Birchmeier, P. Waterhouse, R. Khokha, A. Chambers, S. Yagel, P. K. Lala, D. T. Denhardt, R. Hennes, F. Frantzen, R. Keller, R. Schwartz-Albiez, M. C. Fondaneche, P. Mignatti, R. Tsuboi, E. Robbins, D. B. Rifkin, C. M. Overall, A. Sacchi, R. Falcioni, G. Piaggio, M. G. Rizzo, N. Perrotti, S. J. Kennel, H. Girschick, H. K. Müller-Hermelink, H. P. Vollmers, A. Wenzel, S. Liu, U. Günthert, V. Wesch, M. Giles, H. Ponta, P. Herrlich, B. Stade, U. Hupke, B. Holzmann, J. P. Johnson, A. Sauer, E. Roller, B. Klumpp, N. Güttler, A. Lison, A. Walk, F. Redini, M. Moczar, F. Leoni, M. G. Da Dalt, S. Ménard, S. Canevari, S. Miotti, E. Tagliabue, M. I. Colnaghi, H. Ostmeier, L. Suter, L. Possati, C. Rosciani, E. Recanatini, V. Beatrici, M. Diambrini, M. Polito, U. Rothbächer, L. Eisenbach, D. Plaksin, C. Gelber, G. Kushtai, J. Gubbay, M. Feldman, R. Benke, A. Benedetto, G. Elia, A. Sala, F. Belardelli, J. M. Lehmann, A. Ladanyi, F. -G. Hanisch, J. Sölter, V. Jansen, G. Böhmer, J. Peter-Katalinic, G. Uhlenbruck, R. O'Connor, J. Müller, T. Kirchner, B. Bover, G. Tucker, A. M. Valles, J. Gavrilovic, J. P. Thiery, A. M. Kaufmann, M. Volm, G. Edel, M. Zühlsdorf, H. Voss, B. Wörmann, W. Hiddemann, W. De Neve, D. Van Den Berge, R. Van Loon, G. Storme, L. R. Zacharski, M. Z. Wojtukiewicz, V. Memoli, W. Kisiel, B. J. Kudryk, D. Stump, G. Piñol, M. Gonzalez-Garrigues, A. Fabra, F. Marti, F. Rueda, R. B. Lichtner, K. Khazaie, J. Timar, S. N. Greenzhevskaya, Yu. P. Shmalko, S. E. Hill, R. C. Rees, S. MacNeil, R. Millon, D. Muller, M. Eber, J. Abecassis, M. Betzler, K. P. Bahtsky, V. Yu. Umansky, A. A. Krivorotov, E. K. Balitskaya, O. E. Pridatko, M. I. Smelkova, I. M. Smirnov, B. Korczak, C. Fisher, A. J. Thody, S. D. Young, R. P. Hill, U. Frixen, J. Gopas, S. Segal, G. Hammerling, M. Bar-Eli, B. Rager-Zisman, I. Har-Vardi, Y. Alon, G. J. Hämmerling, M. Perez, I. Algarra, Ma. D. Collado, E. Peran, A. Caballero, F. Garrido, G. A. Turner, M. Blackmore, P. L. Stern, S. Thompson, I. Levin, O. Kuperman, A. Eyal, J. Kaneti, M. Notter, A. Knuth, M. Martin, B. Chauffert, A. Caignard, A. Hammann, F. Martin, M. T. Dearden, H. Pelletier, I. Dransfield, G. Jacob, K. Rogers, G. Pérez-Yarza, M. L. Cañavate, R. Lucas, L. Bouwens, G. Mantovani, F. G. Serri, A. Macciò, M. V. Zucca, G. S. Del Giacco, M. Pérez, K. Kärre, D. Apt, C. Traversari, M. Sensi, G. Carbone, G. Parmiani, P. Hainaut, P. Weynants, G. Degiovanni, T. Boon, P. Marquardt, K. Stulle, T. Wölfel, M. Herin, B. Van den Eynde, E. Klehmann, K. -H. Meyer zum Büschenfelde, M. Samija, M. Gerenčer, D. Eljuga, I. Bašić, C. S. Heacock, A. M. Blake, C. J. D'Aleo, V. L. Alvarez, I. Gresser, C. Maury, J. Moss, D. Woodrow, M. von Ardenne, W. Krüger, P. Möller, H. K. Schachert, T. Itaya, P. Frost, M. Rodolfo, C. Salvi, C. Bassi, E. Huland, H. Huland, G. Sersa, V. Willingham, N. Hunter, L. Milas, H. Schild, P. von Hoegen, B. Mentges, W. Bätz, N. Suzuki, T. Mizukoshi, G. Sava, V. Ceschia, G. Zabucchi, H. Farkas-Himsley, O. Schaal, T. Klenner, B. Keppler, A. Alvarez-Diaz, J. P. Bizzari, F. Barbera-Guillem, B. Osterloh, R. Bartkowski, H. LÖhrke, E. Schwahn, A. Schafmayer, K. Goerttler, C. Cillo, V. Ling, R. Giavazzi, A. Vecchi, W. Luini, A. Garofalo, M. Iwakawa, C. Arundel, P. Tofilon, T. Giraldi, L. Perissin, S. Zorzet, P. Piccini, S. Pacor, V. Rapozzi, U. Fink, H. Zeuner, H. Dancygier, M. Classen, C. Lersch, M. Reuter, C. Hammer, W. Brendel, G. Mathé, C. Bourut, E. Chenu, Y. Kidani, Y. Mauvernay, A. V. Schally, P. Reizenstein, J. Gastiaburu, A. M. Comaru-Schally, D. Cupissol, C. Jasmin, J. L. Missot, F. Wingen, D. Schmähl, C. Pauwels-Vergely, M. -F. Poupon, T. B. Gasic, J. I. Ewaskiewicz, G. J. Gasic, J. Pápay, R. Mauvernay, A. Schally, R. Keiling, R. Hagipantelli, M. Busuttil, M. L. VoVan, J. L. Misset, F. Lévi, M. Musset, P. Ribaud, P. Hilgard, T. Reissmann, J. Stekar, R. Voegeli, W. Den Otter, H. A. Maas, H. F. J. Dullens, R. L. Merriman, L. R. Tanzer, K. A. Shackelford, K. G. Bemis, J. B. Campbell, and K. Matsumoto
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 1988
- Full Text
- View/download PDF
33. Structural and functional aspects of Kupffer cells
- Author
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L, Bouwens
- Subjects
Kupffer Cells ,Animals ,Humans - Abstract
Methods are now available to characterize Kupffer cells both in vivo and in vitro. They can be isolated and purified from the liver and their functional activities studied in maintenance culture. Kupffer cells are not merely phagocytic cells or scavengers but they can also produce and secrete a variety of substances that can regulate the functions of other cells. They can also regulate the immune system and be directly cytotoxic to tumor cells and parasites. In the light of these reported functions, the clinical importance of Kupffer cells in a variety of liver diseases deserves to be better explored. Although the origin and cytokinetics of Kupffer cells, and specially their relation to the Mononuclear Phagocyte System (MPS), are still not completely understood, it has now become clear that Kupffer cells are not end-cells incapable of self-proliferation. Under various experimental conditions Kupffer cells have been shown to respond to activation by strong mitotic proliferation. On the other hand, bone marrow-derived cells can migrate to the liver under certain conditions and differentiate into liver macrophages, thus becoming Kupffer cells.
- Published
- 1988
34. Cell biology and kinetics of Kupffer cells in the liver
- Author
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K, Wake, K, Decker, A, Kirn, D L, Knook, R S, McCuskey, L, Bouwens, and E, Wisse
- Subjects
Endotoxins ,Kupffer Cells ,Cell Cycle ,Animals ,Humans ,Arachidonic Acids ,Infections ,Lysosomes ,Endocytosis - Published
- 1989
35. Proliferation and phenotypic expression of non-parenchymal liver cells
- Author
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L. Bouwens
- Subjects
In situ ,Pathology ,medicine.medical_specialty ,Liver cytology ,Kupffer Cells ,Population ,Biology ,Sinusoid ,Fibrosis ,medicine ,Animals ,Endothelium ,education ,Mitosis ,education.field_of_study ,Cell Cycle ,Gastroenterology ,medicine.disease ,Phenotype ,In vitro ,Cell biology ,Liver Regeneration ,Rats ,Killer Cells, Natural ,Microscopy, Electron ,Liver ,Cell Division - Abstract
The four types of non-parenchymal sinusoid lining cells can be identified in situ and can be isolated for in vitro studies: the fenestrated endothelial cells, the phagocytic Kupffer cells, the fibroblast-like fat-storing cells, and the 'natural killer' pit cells. In situ the last three sinusoidal cell types can be seen to proliferate and increase in number in experimental models of liver pathology, such as inflammations and fibrosis. The understanding of the population dynamics of these cells--their mitotic activity, turnover time, and migration--may therefore have clinical applications. In the present article our data concerning the proliferation kinetics of Kupffer and pit cells in rat liver are reviewed.
- Published
- 1988
36. Resolution of Acinar Dedifferentiation Regulates Tissue Remodeling in Pancreatic Injury and Cancer Initiation.
- Author
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Baldan J, Camacho-Roda J, Ballester M, Høj K, Kurilla A, Maurer HC, Arcila-Barrera S, Lin X, Pan Z, Castro JL, Mayorca-Guiliani AE, Rift CV, Hasselby J, Bouwens L, Lefebvre V, David CJ, Parnas O, DelGiorno KE, Erler JT, Rooman I, and Arnes L
- Subjects
- Animals, Mice, Humans, Pancreatitis pathology, Pancreatitis genetics, Pancreatitis metabolism, SOXC Transcription Factors genetics, SOXC Transcription Factors metabolism, Disease Models, Animal, Pancreas pathology, Pancreas metabolism, Cell Transformation, Neoplastic pathology, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Carcinoma in Situ pathology, Carcinoma in Situ genetics, Carcinoma in Situ metabolism, Transcriptome, Pancreatic Neoplasms pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Acinar Cells pathology, Acinar Cells metabolism, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal metabolism, Metaplasia genetics, Metaplasia pathology, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Cell Dedifferentiation, Ceruletide
- Abstract
Background & Aims: Acinar-to-ductal metaplasia (ADM) is crucial in the development of pancreatic ductal adenocarcinoma. However, our understanding of the induction and resolution of ADM remains limited. We conducted comparative transcriptome analyses to identify conserved mechanisms of ADM in mouse and human., Methods: We identified Sox4 among the top up-regulated genes. We validated the analysis by RNA in situ hybridization. We performed experiments in mice with acinar-specific deletion of Sox4 (Ptf1a: CreER; Rosa26
-LSL-YFPLSL-YFP ; Sox4fl/fl ) with and without an activating mutation in Kras (KrasLSL-G12D/+ ). Mice were given caerulein to induce pancreatitis. We performed phenotypic analysis by immunohistochemistry, tissue decellularization, and single-cell RNA sequencing., Results: We demonstrated that Sox4 is reactivated in ADM and pancreatic intraepithelial neoplasias. Contrary to findings in other tissues, Sox4 actually counteracts cellular dedifferentiation and helps maintain tissue homeostasis. Moreover, our investigations unveiled the indispensable role of Sox4 in the specification of mucin-producing cells and tuft-like cells from acinar cells. We identified Sox4-dependent non-cell-autonomous mechanisms regulating the stromal reaction during disease progression. Notably, Sox4-inferred targets are activated upon KRAS inactivation and tumor regression., Conclusions: Our results indicate that our transcriptome analysis can be used to investigate conserved mechanisms of tissue injury. We demonstrate that Sox4 restrains acinar dedifferentiation and is necessary for the specification of acinar-derived metaplastic cells in pancreatic injury and cancer initiation and is activated upon Kras ablation and tumor regression in mice. By uncovering novel potential strategies to promote tissue homeostasis, our findings offer new avenues for preventing the development of pancreatic ductal adenocarcinoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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37. Vulnerability profiles of workers and the relation with burnout symptoms: results from the Netherlands working conditions survey.
- Author
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Bouwens L, van Zon SKR, Peijen R, and Vooijs M
- Subjects
- Humans, Netherlands epidemiology, Female, Male, Adult, Cross-Sectional Studies, Middle Aged, Surveys and Questionnaires, Educational Status, Employment psychology, Employment statistics & numerical data, Young Adult, Working Conditions, Workload psychology, Burnout, Professional epidemiology, Burnout, Professional psychology, Workplace psychology
- Abstract
Introduction: Unfavorable working conditions may place workers in a vulnerable position in the labour market, but studies on the clustering of these factors and their relation to burnout symptoms are lacking. This study aims to identify subgroups of workers in potentially vulnerable positions in the labour market and examine whether burnout symptoms differ across the established subgroups., Methods: This study utilizes cross-sectional data from 2019 of the Netherlands Working Conditions Survey (n = 55,283). Working conditions included employment contracts, working hours, multiple jobs, tenure, physical strain, autonomy, and workload. Burnout symptoms were measured with five items on a 7-point Likert scale. Latent Class Analysis was used to identify vulnerability subgroups based on working conditions and educational level. Wilcoxon rank-sum tests were used to examine whether burnout symptoms differed between the identified subgroups., Results: Three out of nine subgroups (i.e., classes 4, 6, and 7) presented combinations of multiple unfavourable working conditions. The vulnerability of class 4, characterized by low educational level, physically demanding work, low autonomy, and a high workload, was underscored by a significantly higher burnout symptom score (M = 2.91;SD = 0.97) compared to all other subgroups. Subgroups 3 (M = 2.69;SD = 1.43) and 8 (M = 2.41;SD = 1.41), without striking unfavourable conditions, had the second and third highest scores on burnout symptoms., Conclusions: Determining vulnerability in the labour market is not straightforward as not all profiles that presented clusters of unfavourable working conditions scored high on burnout symptoms, and vice versa. Future research should investigate whether findings are similar to other mental health outcomes., (© 2024. The Author(s).)
- Published
- 2024
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38. Multilevel Mindfulness: Which Organizational Factors Stimulate Mindfulness in the Workplace?
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Koopmans L, Bruel D, de Geit E, van den Bergh R, Bouwens L, de Korte E, Wiezer N, and van der Torre W
- Subjects
- Humans, Occupational Stress prevention & control, Occupational Stress psychology, Qualitative Research, Occupational Health, Organizational Culture, Interviews as Topic, Male, Female, Mindfulness, Workplace psychology
- Abstract
Objective: This study aimed to examine which factors in the organizational context stimulate and/or hinder employee mindfulness. Methods: Two methods were used: 1) scientific literature review, and 2) qualitative interviews with scientists, trainers, and managers. Results: The individual and the work environment interact with each other when it comes to mindfulness in the workplace. Factors at the task, team, supervisor, organizational, and context level stimulate employee mindfulness. Conclusions: Mindfulness is effective in dealing with stress but also positively impacts work-related outcomes such as engagement, concentration, and productivity. A multilevel approach can strengthen the positive effects of individual mindfulness training in the workplace, ultimately contributing to healthy workplaces., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)
- Published
- 2024
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39. Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation.
- Author
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De Vlaminck K, Van Hove H, Kancheva D, Scheyltjens I, Pombo Antunes AR, Bastos J, Vara-Perez M, Ali L, Mampay M, Deneyer L, Miranda JF, Cai R, Bouwens L, De Bundel D, Caljon G, Stijlemans B, Massie A, Van Ginderachter JA, Vandenbroucke RE, and Movahedi K
- Subjects
- Humans, Monocytes metabolism, Microglia metabolism, Brain, Neuroinflammatory Diseases, Macrophages metabolism
- Abstract
Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells. Here, we examined the fate of microglia, BAMs, and recruited macrophages upon neuroinflammation and through resolution. Upon infection, Trypanosoma brucei parasites invaded the brain via its border regions, triggering brain barrier disruption and monocyte infiltration. Fate mapping combined with single-cell sequencing revealed microglia accumulation around the ventricles and expansion of epiplexus cells. Depletion experiments using genetic targeting revealed that resident macrophages promoted initial parasite defense and subsequently facilitated monocyte infiltration across brain barriers. These recruited monocyte-derived macrophages outnumbered resident macrophages and exhibited more transcriptional plasticity, adopting antimicrobial gene expression profiles. Recruited macrophages were rapidly removed upon disease resolution, leaving no engrafted monocyte-derived cells in the parenchyma, while resident macrophages progressively reverted toward a homeostatic state. Long-term transcriptional alterations were limited for microglia but more pronounced in BAMs. Thus, brain-resident and recruited macrophages exhibit diverging responses and dynamics during infection and resolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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40. In vitro comparison of various antioxidants and flavonoids from Rooibos as beta cell protectants against lipotoxicity and oxidative stress-induced cell death.
- Author
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Moens C, Muller CJF, and Bouwens L
- Subjects
- Antioxidants analysis, Antioxidants pharmacology, Cell Death, Exenatide pharmacology, Flavonoids analysis, Flavonoids pharmacology, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, Oxidative Stress, Plant Extracts pharmacology, Plant Extracts therapeutic use, Protective Agents pharmacology, Aspalathus, Diabetes Mellitus, Type 2 drug therapy, Insulin-Secreting Cells
- Abstract
Oxidative stress and lipotoxicity effects on pancreatic β cells play a major role in the pathogenesis of type 2 diabetes (T2D). Flavonoids and antioxidants are under study for their cytoprotective effects and antidiabetic potential. In this study, we aimed to compare the protective effect of the Rooibos components aspalathin, isoorientin, 3-hydroxyphloretin (3-OH) and green Rooibos extract (GRT) itself, and exendin-4 and N-acetylcysteine (NAC) as reference molecules, against lipotoxicity and oxidative stress. The insulin-producing β cell line INS1E was exposed to hydrogen peroxide or streptozotocin (STZ) to induce oxidative stress, and palmitate to induce lipotoxicity. Cell viability was assessed by a MTS cell viability assay. Antioxidant response and antiapoptotic gene expression was performed by qRT-PCR. Glucose transporter 2 (GLUT 2) transporter inhibition was assessed through 2-NBDG uptake. GRT and the flavonoids aspalathin and 3-hydroxyphloretin offered significant protection against oxidative stress and lipotoxicity. GRT downregulated expression of pro-apoptotic genes Txnip and Ddit3. The flavonoids aspalathin and 3-hydroxyphloretin also downregulated these genes and in addition upregulated expression of antioxidant response genes Hmox1, Nqo1 and Sod1. Isoorientin gave no cytoprotection. Cytoprotection by Rooibos components was significantly higher than by NAC or exendin-4. Rooibos components strongly protect INS1E β cells against diabetogenic stress. Cytoprotection was associated with the upregulation of antioxidant response genes of the NRF2/KEAP1 pathway or suppression of the TXN system. The Rooibos molecules offered better protection against these insults than exendin-4 and NAC, making them interesting candidates as β cell cytoprotectants for therapeutic or nutraceutical applications., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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41. Transcutaneous Vagal Nerve Stimulation Alone or in Combination With Radiotherapy Stimulates Lung Tumor Infiltrating Lymphocytes But Fails to Suppress Tumor Growth.
- Author
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Reijmen E, De Mey S, Van Damme H, De Ridder K, Gevaert T, De Blay E, Bouwens L, Collen C, Decoster L, De Couck M, Laoui D, De Grève J, De Ridder M, Gidron Y, and Goyvaerts C
- Subjects
- Aged, Animals, Carcinoma, Lewis Lung immunology, Carcinoma, Lewis Lung pathology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung pathology, Combined Modality Therapy, Female, Humans, Lung Neoplasms immunology, Lung Neoplasms pathology, Lymphocytes, Tumor-Infiltrating immunology, Male, Mice, Inbred C57BL, Middle Aged, Tumor Burden, Mice, Carcinoma, Lewis Lung radiotherapy, Carcinoma, Lewis Lung therapy, Carcinoma, Non-Small-Cell Lung radiotherapy, Carcinoma, Non-Small-Cell Lung therapy, Lung Neoplasms radiotherapy, Lung Neoplasms therapy, Vagus Nerve Stimulation
- Abstract
The combination of radiotherapy (RT) with immunotherapy represents a promising treatment modality for non-small cell lung cancer (NSCLC) patients. As only a minority of patients shows a persistent response today, a spacious optimization window remains to be explored. Previously we showed that fractionated RT can induce a local immunosuppressive profile. Based on the evolving concept of an immunomodulatory role for vagal nerve stimulation (VNS), we tested its therapeutic and immunological effects alone and in combination with fractionated RT in a preclinical-translational study. Lewis lung carcinoma-bearing C57Bl/6 mice were treated with VNS, fractionated RT or the combination while a patient cohort with locally advanced NSCLC receiving concurrent radiochemotherapy (ccRTCT) was enrolled in a clinical trial to receive either sham or effective VNS daily during their 6 weeks of ccRTCT treatment. Preclinically, VNS alone or with RT showed no therapeutic effect yet VNS alone significantly enhanced the activation profile of intratumoral CD8
+ T cells by upregulating their IFN-γ and CD137 expression. In the periphery, VNS reduced the RT-mediated rise of splenic, but not blood-derived, regulatory T cells (Treg) and monocytes. In accordance, the serological levels of protumoral CXCL5 next to two Treg-attracting chemokines CCL1 and CCL22 were reduced upon VNS monotherapy. In line with our preclinical findings on the lack of immunological changes in blood circulating immune cells upon VNS, immune monitoring of the peripheral blood of VNS treated NSCLC patients (n=7) did not show any significant changes compared to ccRTCT alone. As our preclinical data do suggest that VNS intensifies the stimulatory profile of the tumor infiltrated CD8+ T cells, this favors further research into non-invasive VNS to optimize current response rates to RT-immunotherapy in lung cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reijmen, De Mey, Van Damme, De Ridder, Gevaert, De Blay, Bouwens, Collen, Decoster, De Couck, Laoui, De Grève, De Ridder, Gidron and Goyvaerts.)- Published
- 2021
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42. MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions.
- Author
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Backx E, Wauters E, Baldan J, Van Bulck M, Michiels E, Heremans Y, De Paep DL, Kurokawa M, Goyama S, Bouwens L, Jacquemin P, Houbracken I, and Rooman I
- Subjects
- Animals, Cell Dedifferentiation, Disease Models, Animal, Humans, Mice, Signal Transduction, Acinar Cells metabolism, Cell Death genetics, MDS1 and EVI1 Complex Locus Protein metabolism, Oncogenes genetics
- Abstract
Maintenance of the pancreatic acinar cell phenotype suppresses tumor formation. Hence, repetitive acute or chronic pancreatitis, stress conditions in which the acinar cells dedifferentiate, predispose for cancer formation in the pancreas. Dedifferentiated acinar cells acquire a large panel of duct cell-specific markers. However, it remains unclear to what extent dedifferentiated acini differ from native duct cells and which genes are uniquely regulating acinar cell dedifferentiation. Moreover, most studies have been performed on mice since the availability of human cells is scarce. Here, we applied a non-genetic lineage tracing method of human pancreatic exocrine acinar and duct cells that allowed cell-type-specific gene expression profiling by RNA sequencing. Subsequent to this discovery analysis, one transcription factor that was unique for dedifferentiated acinar cells was functionally characterized. RNA sequencing analysis showed that human dedifferentiated acinar cells expressed genes in "Pathways of cancer" with a prominence of MECOM (EVI-1), a transcription factor that was not expressed by duct cells. During mouse embryonic development, pre-acinar cells also transiently expressed MECOM and in the adult mouse pancreas, MECOM was re-expressed when mice were subjected to acute and chronic pancreatitis, conditions in which acinar cells dedifferentiate. In human cells and in mice, MECOM expression correlated with and was directly regulated by SOX9. Mouse acinar cells that, by genetic manipulation, lose the ability to upregulate MECOM showed impaired cell adhesion, more prominent acinar cell death, and suppressed acinar cell dedifferentiation by limited ERK signaling. In conclusion, we transcriptionally profiled the two major human pancreatic exocrine cell types, acinar and duct cells, during experimental stress conditions. We provide insights that in dedifferentiated acinar cells, cancer pathways are upregulated in which MECOM is a critical regulator that suppresses acinar cell death by permitting cellular dedifferentiation., (© 2021. The Author(s).)
- Published
- 2021
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43. Fractionated Radiation Severely Reduces the Number of CD8+ T Cells and Mature Antigen Presenting Cells Within Lung Tumors.
- Author
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Reijmen E, De Mey S, De Mey W, Gevaert T, De Ridder K, Locy H, Martens S, De Blay E, Bouwens L, Debie P, Breckpot K, De Grève J, De Ridder M, and Goyvaerts C
- Subjects
- Animals, Female, Lung Neoplasms immunology, Lung Neoplasms pathology, Mice, Mice, Inbred C57BL, Antigen-Presenting Cells radiation effects, CD8-Positive T-Lymphocytes radiation effects, Dose Fractionation, Radiation, Lung Neoplasms radiotherapy
- Abstract
Purpose: The combination of standard-of-care radiation therapy (RT) with immunotherapy is moving to the mainstream of non-small cell lung cancer treatment. Multiple preclinical studies reported on the CD8
+ T cell stimulating properties of RT, resulting in abscopal therapeutic effects. A literature search demonstrates that most preclinical lung cancer studies applied subcutaneous lung tumor models. Hence, in-depth immunologic evaluation of clinically relevant RT in orthotopic lung cancer models is lacking., Methods and Materials: We studied the therapeutic and immunologic effects of low-dose fractionated RT on lungs from C57BL/6 mice, challenged 2 weeks before with firefly luciferase expressing Lewis lung carcinoma cells via the tail vein. Low-dose fractionation was represented by 4 consecutive daily fractions of image guided RT at 3.2 Gy., Results: We showed reduced lung tumor growth upon irradiation using in vivo bioluminescence imaging and immunohistochemistry. Moreover, significant immunologic RT-induced changes were observed in irradiated lungs and in the periphery (spleen and blood). First, a significant decrease in the number of CD8+ T cells and trends toward more CD4+ and regulatory T cells were seen after RT in all evaluated tissues. Notably, only in the periphery did the remaining CD8+ T cells show a more activated phenotype. In addition, a significant expansion of neutrophils and monocytes was observed upon RT locally and systemically. Locally, RT increased the influx of tumor-associated macrophages and conventional type 2 dendritic cells, whereas the alveolar macrophages and conventional type 1 DCs dramatically decreased. Functionally, these antigen-presenting cells severely reduced their CD86 expression, suggesting a reduced capacity to induce potent immunity., Conclusions: Our results imply that low-dose fractionated RT of tumor-bearing lung tissue shifts the immune cell balance toward an immature myeloid cell dominating profile. These data argue for myeloid cell repolarizing strategies to enhance the abscopal effects in patients with non-small cell lung cancer treated with fractionated RT., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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44. Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease.
- Author
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Martens S, Coolens K, Van Bulck M, Arsenijevic T, Casamitjana J, Fernandez Ruiz A, El Kaoutari A, Martinez de Villareal J, Madhloum H, Esni F, Heremans Y, Leuckx G, Heimberg H, Bouwens L, Jacquemin P, De Paep DL, In't Veld P, D'Haene N, Bouchart C, Dusetti N, Van Laethem JL, Waelput W, Lefesvre P, Real FX, Rovira M, and Rooman I
- Abstract
Objective: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63
+ basal cells reportedly do not exist in the normal pancreas., Design: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed., Results: In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme., Conclusion: In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2021
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45. Dynamic Regulation of Expression of KRAS and Its Effectors Determines the Ability to Initiate Tumorigenesis in Pancreatic Acinar Cells.
- Author
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Assi M, Achouri Y, Loriot A, Dauguet N, Dahou H, Baldan J, Libert M, Fain JS, Guerra C, Bouwens L, Barbacid M, Lemaigre FP, and Jacquemin P
- Subjects
- Acinar Cells metabolism, Animals, Apoptosis, Biomarkers, Tumor genetics, CRISPR-Cas Systems, Cell Proliferation, Disease Models, Animal, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Humans, Male, Mice, Pancreatic Neoplasms etiology, Pancreatic Neoplasms metabolism, Pancreatitis etiology, Pancreatitis metabolism, Proto-Oncogene Proteins p21(ras) antagonists & inhibitors, Proto-Oncogene Proteins p21(ras) genetics, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Acinar Cells pathology, Biomarkers, Tumor metabolism, Gene Expression Regulation, Neoplastic, Mutation, Pancreatic Neoplasms pathology, Pancreatitis pathology, Proto-Oncogene Proteins p21(ras) metabolism
- Abstract
Pancreatic acinar cells are a cell type of origin for pancreatic cancer that become progressively less sensitive to tumorigenesis induced by oncogenic Kras mutations after birth. This sensitivity is increased when Kras mutations are combined with pancreatitis. Molecular mechanisms underlying these observations are still largely unknown. To identify these mechanisms, we generated the first CRISPR-edited mouse models that enable detection of wild-type and mutant KRAS proteins in vivo . Analysis of these mouse models revealed that more than 75% of adult acinar cells are devoid of detectable KRAS protein. In the 25% of acinar cells expressing KRAS protein, transcriptomic analysis highlighted a slight upregulation of the RAS and MAPK pathways. However, at the protein level, only marginal pancreatic expression of essential KRAS effectors, including C-RAF, was observed. The expression of KRAS and its effectors gradually decreased after birth. The low sensitivity of adult acinar cells to Kras mutations resulted from low expression of KRAS and its effectors and the subsequent lack of activation of RAS/MAPK pathways. Pancreatitis triggered expression of KRAS and its effectors as well as subsequent activation of downstream signaling; this induction required the activity of EGFR. Finally, expression of C-RAF in adult pancreas was required for pancreatic tumorigenesis. In conclusion, our study reveals that control of the expression of KRAS and its effectors regulates the sensitivity of acinar cells to transformation by oncogenic Kras mutations. SIGNIFICANCE: This study generates new mouse models to study regulation of KRAS during pancreatic tumorigenesis and highlights a novel mechanism through which pancreatitis sensitizes acinar cells to Kras mutations., (©2021 American Association for Cancer Research.)
- Published
- 2021
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46. Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization.
- Author
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Pombo Antunes AR, Scheyltjens I, Lodi F, Messiaen J, Antoranz A, Duerinck J, Kancheva D, Martens L, De Vlaminck K, Van Hove H, Kjølner Hansen SS, Bosisio FM, Van der Borght K, De Vleeschouwer S, Sciot R, Bouwens L, Verfaillie M, Vandamme N, Vandenbroucke RE, De Wever O, Saeys Y, Guilliams M, Gysemans C, Neyns B, De Smet F, Lambrechts D, Van Ginderachter JA, and Movahedi K
- Subjects
- Animals, Humans, Mice, Single-Cell Analysis, Brain Neoplasms immunology, Glioblastoma immunology, Tumor-Associated Macrophages cytology, Tumor-Associated Macrophages immunology
- Abstract
Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remain poorly understood. Here, we employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and dynamic across disease stages. Tumor-associated macrophages (TAMs) consisted of microglia- or monocyte-derived populations, with both exhibiting additional heterogeneity, including subsets with conserved lipid and hypoxic signatures. Microglia- and monocyte-derived TAMs were self-renewing populations that competed for space and could be depleted via CSF1R blockade. Microglia-derived TAMs were predominant in newly diagnosed tumors, but were outnumbered by monocyte-derived TAMs following recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions.
- Published
- 2021
- Full Text
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47. Aspalathin Protects Insulin-Producing β Cells against Glucotoxicity and Oxidative Stress-Induced Cell Death.
- Author
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Moens C, Bensellam M, Himpe E, Muller CJF, Jonas JC, and Bouwens L
- Subjects
- Animals, Cell Death drug effects, Cells, Cultured, Chalcones administration & dosage, Dose-Response Relationship, Drug, Gene Expression Regulation drug effects, Glucose toxicity, Heme Oxygenase (Decyclizing) genetics, Hydrogen Peroxide toxicity, Male, Oxidative Stress genetics, Rats, Wistar, Streptozocin toxicity, Chalcones pharmacology, Insulin-Secreting Cells drug effects, Oxidative Stress drug effects, Protective Agents pharmacology
- Abstract
Scope: Aspalathin, the main polyphenolic phytochemical of rooibos (Aspalathus linearis), has been attributed with health promoting properties, including a glucose lowering effect that can prove interesting for application as nutraceutical or therapeutic in (pre-)diabetics. Preservation of β cell mass in the pancreas is considered a key issue for diabetes prevention or treatment, therefore the aim is to investigate whether aspalathin also has β cell cytoprotective potential., Methods and Results: Rat pancreatic islets and the β cell line Insulinoma 1E (INS1E) are studied in vitro after exposure to various cytotoxic agents, namely streptozotocin (STZ), hydrogen peroxide, or chronic high glucose. The effect of aspalathin on cell survival and apoptosis is studied. Expression of relevant cytoprotective genes is analyzed by qRT-PCR and proteins by Western blot. Aspalathin is found to protect β cells against cytotoxicity and apoptosis. This is associated with increased translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and expression of its antioxidant target genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo-1), and superoxide dismutase 1 (Sod1)., Conclusion: It is proposed that aspalathin protects β cells against glucotoxicity and oxidative stress by increasing the expression of NRF2-regulated antioxidant enzymes. This indicates that aspalathin is an interesting β cell cytoprotectant., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2020
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48. Retraction Note: Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice.
- Author
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Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CVE, Van de Casteele M, German MS, Bouwens L, and Heimberg H
- Abstract
This article has been retracted; see accompanying Retraction Note, which can be accessed via a link at the top of the paper.
- Published
- 2020
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49. Measuring the Pancreatic β Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis.
- Author
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Joosten L, Brom M, Peeters H, Bos D, Himpe E, Bouwens L, Boerman O, and Gotthardt M
- Subjects
- Animals, Autoradiography, Diabetes Mellitus, Type 1 diagnostic imaging, Disease Models, Animal, Female, Immunohistochemistry, Indium Radioisotopes administration & dosage, Indium Radioisotopes chemistry, Indium Radioisotopes metabolism, Injections, Intravenous, Mice, Mice, Inbred NOD, Pentetic Acid administration & dosage, Pentetic Acid chemistry, Pentetic Acid metabolism, Peptides administration & dosage, Peptides chemistry, Radiopharmaceuticals metabolism, Tissue Distribution, Diabetes Mellitus, Type 1 metabolism, Hyperglycemia metabolism, Insulin-Secreting Cells metabolism, Peptides metabolism, Tomography, Emission-Computed, Single-Photon methods
- Abstract
Objective: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the β cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice., Methods: NOD mice ( n = 75, 7-21 weeks old) were injected intravenously with [
111 In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [111 In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the β cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed., Results: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [111 In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM., Conclusions: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.- Published
- 2019
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50. Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture.
- Author
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Baldan J, Houbracken I, Rooman I, and Bouwens L
- Subjects
- Acinar Cells metabolism, Adult, Antigens, Tumor-Associated, Carbohydrate metabolism, Biomarkers metabolism, Cell Plasticity, Cells, Cultured, GPI-Linked Proteins metabolism, Homeodomain Proteins metabolism, Humans, Pancreas, Exocrine metabolism, Plant Lectins chemistry, SOX9 Transcription Factor metabolism, Thromboplastin metabolism, Trans-Activators metabolism, Acinar Cells cytology, Cell Lineage, Pancreas, Exocrine cytology
- Abstract
Human pancreatic exocrine cells were cultured in 3D suspension and formed pancreatospheres composed of acinar-derived and duct-like cells. We investigated, up to 6 days, the fate of human pancreatic acinar cells using fluorescein-conjugated Ulex Europaeus Agglutinin 1 lectin, a previously published acinar-specific non-genetic lineage tracing strategy. At day 4, fluorescence-activated cell sort for the intracellularly incorporated FITC-conjugated UEA1 lectin and the duct-specific CA19.9 surface marker, distinguished acinar-derived cells (UEA1
+ CA19.9- ) from duct-like cells (UEA1- CA19.9+ ) and acinar-to-duct-like transdifferentiated cells (UEA1+ CA19.9+ ). mRNA expression analysis of the acinar-derived (UEA1+ CA19.9- ) and duct-like (UEA1- CA19.9+ ) cell fractions with concomitant immunocytochemical analysis of the pancreatospheres revealed acquisition of an embryonic signature in the UEA1+ CA19.9- acinar-derived cells characterized by de novo expression of SOX9 and CD142, robust expression of PDX1 and surface expression of GP2. The colocalisation of CD142, a multipotent pancreatic progenitor surface marker, PDX1, SOX9 and GP2 is reminiscent of a cellular state present during human embryonic development. Addition of TGF-beta signalling inhibitor Alk5iII, induced a 28-fold increased KI67-labeling in pancreatospheres, more pronounced in the CD142+ GP2+ acinar-derived cells. These findings with human cells underscore the remarkable plasticity of pancreatic exocrine acinar cells, previously described in rodents, and could find applications in the field of regenerative medicine.- Published
- 2019
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