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Gayban, A.J.B. (author), Souza, L.A.C. (author), Cooper, S.G. (author), Regalado, E. (author), Kleemann, R. (author), Earley, Y.F. (author)Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic...article 2023
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van Kampen, J. (author), Lammers, M. (author), Steijn, W. (author), Guldenmund, F. (author), Groeneweg, J. (author)In the Netherlands, approximately 2.300 workers have a serious reportable accident at work every year, of which around 60 are fatal (Inspectie SZW, 2020; Bellamy et al., 2014). Safety practitioners employ many methods to improve occupational safety for workers within their companies. Interventions might, for example, be aimed at improving...article 2023
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Streekstra, E.J. (author), Kiss, M. (author), van den Heuvel, J. (author), Nicolaï, J. (author), van den Broek, P. (author), Botden, S.M.B.I. (author), Stommel, M.W.J. (author), van Rijssel, L. (author), Ungell, A.L. (author), van de Steeg, E. (author), Russel, F.G.M. (author), de Wildt, S.N. (author)Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport across tissue barriers, but it has not been used to study drug absorption processes in children. This study aimed to explore the feasibility of the Ussing chamber methodology to assess...article 2022
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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...article 2022
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- Hooftman, W.E. (author), Peijen, R. (author), Soeter, M. (author), Blokland, M. (author), Tuithof, M. (author) report 2022
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Ostendorf, R. (author), Erpelinck, S. (author)The Organ-on-a-Chip Early Research Program enables TNO to offer state-of-the-art technologies that help the pharmaceutical industry advance drug development. An accurate, viable alternative to animal testing, on-a-chip technologies model human tissue functioning and accelerate compound development and testing. The Intestinal Epithelial Barrier...other 2022
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Ostendorf, R. (author)The Organ-on-a-Chip Early Research Program (ERP) has enabled TNO to offer a number of state-of-the-art technologies to help pharmaceutical and biotech companies advance and accelerate drug development. An accurate, viable alternative to animal testing, on-a-chip technologies model the workings of human tissue and accelerate compound development...other 2022
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van Berlo, D. (author), van de Steeg, E. (author), Amirabadi, H.E. (author), Masereeuw, R. (author)The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In...article 2021
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Stevens, L.J. (author), Zhu, A.Z.X. (author), Chothe, P.P. (author), Chowdhury, S.K. (author), Donkers, J.M. (author), Vaes, W.H.J. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion and plasma exposure of drugs. For this evaluation we dosed...article 2021
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Pagan, L. (author), Ederveen, R.A.M. (author), Huisman, B.W. (author), Schoones, J.W. (author), Zwittink, R.D. (author), Schuren, F.H.J. (author), Rissmann, R. (author), Piek, J.M.J. (author), van Poelgeest, M.I.E. (author)The link between cancer and the microbiome is a fast-moving field in research. There is little knowledge on the microbiome in ((pre)malignant) conditions of the vulvar skin. This systematic review aims to provide an overview of the literature regarding the microbiome composition of the healthy vulvar skin and in (pre)malignant vulvar disease....article 2021
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Patel, N. (author), Adelman, D.C. (author), Anagnostou, K. (author), Baumert, J.L. (author), Blom, W.M. (author), Campbell, D.E. (author), Chinthrajah, R.S. (author), Mills, E.N.C. (author), Javed, B. (author), Purington, N. (author), Remington, B.C. (author), Sampson, H.A. (author), Smith, A.D. (author), Yarham, R.A.R. (author), Turner, P.J. (author)Background Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of...article 2021
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Bourgonje, A.R. (author), Offringa, A.K. (author), van Eijk, L.E. (author), Abdulle, A.E. (author), Hillebrands, J.L. (author), van der Voort, P.H.J. (author), van Goor, H. (author), van Hezik, E.J. (author)Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a...article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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Offringa, A. (author), Montijn, R. (author), Singh, S. (author), Paul, M. (author), Pinto, Y.M. (author), Pinto-Sietsma, S.J. (author)The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the...article 2020
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van den Dries, M.A. (author), Guxens, M. (author), Spaan, S. (author), Ferguson, K.K. (author), Philips, E. (author), Santos, S. (author), Jaddoe, V.W.V. (author), Ghassabian, A. (author), Trasande, L. (author), Tiemeier, H. (author), Pronk, A. (author)BACKGROUND: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the...article 2020
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Moné, M.J. (author), Pallocca, G. (author), Escher, S.E. (author), Exner, T. (author), Herzler, M. (author), Hougaard Bennekou, S. (author), Kamp, H. (author), Kroese, E.D. (author), Leist, M. (author), Steger-Hartmann, T. (author), van de Water, B. (author)In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain...article 2020
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van Bilsen, J.H.M. (author), Dulos, R. (author), van Stee, M.F. (author), Meima, M.Y. (author), Rouhani Rankouhi, T. (author), Neergaard Jacobsen, L. (author), Staudt Kvistgaard, A. (author), Garthoff, J.A. (author), Knippels, L.M.J. (author), Knipping, K. (author), Houben, G.F. (author), Verschuren, L. (author), Meijerink, M. (author), Krishnan, S. (author)A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into...article 2020
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Sewell, F. (author), Strupp, C. (author), van der Laan, J.W. (author), Wolf, D.C. (author), Wolterink, G. (author), Woutersen, R. (author), Zvonar, Z. (author), Heusinkveld, H. (author), Braakhuis, H. (author)Currently the only methods for non-genotoxic carcinogenic hazard assessment accepted by most regulatory authorities are lifetime carcinogenicity studies. However, these involve the use of large numbers of animals and the relevance of their predictive power and results has been scientifically challenged. With increased availability of innovative...article 2020
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Pouwer, M.G. (author), Pieterman, E.J. (author), Worms, N. (author), Keijzer, N. (author), Jukema, J.W. (author), Gromada, J. (author), Gusarova, V. (author), Princen, H.M.G. (author)Atherosclerosis-related cardiovascular disease causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab-monoclonal...article 2020
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Tielman, M.L. (author), Neerincx, M.A. (author), Pagliari, C. (author), Rizzo, A. (author), Brinkman, W.P. (author)Background: Digital health interventions can fill gaps in mental healthcare provision. However, autonomous e-mental health (AEMH) systems also present challenges for effective risk management. To balance autonomy and safety, AEMH systems need to detect risk situations and act on these appropriately. One option is sending automatic alerts to...article 2019